JPH03218350A - Pantothenic acid derivative - Google Patents

Abstract

NEW MATERIAL:A compound of formula I [R<1>, R<2> are H, OH-protecting group; R<3> is 5-25C monovalent aliphatic hydrocarbon group, NHR<4> (R<4> is 5-25C monovalent aliphatic hydrocarbon group); one of X, Y is 4-7 membered divalent nitrogen-containing heterocyclic ring group, the other is O, S, HR<6> (R<6> is H, lower alkyl); (m) is 0-2; (n) is 1-4]. EXAMPLE:2-Decanoylaminomethyl-1-[3-[N-2,2,5,5-tetramethyl-1,3-dioxane-4- carbonylamino]-propanoyl]pyrrolidine. USE:An acyl CoA-cholesterol-acyl transition enzyme-inhibiting agent. A drug having a blood lipid-lowering activity based on a cholesterol absorption inhibition and simultaneously an anti-arteriosclerosis activity. PREPARATION:For example, a compound of formula II (R<11>, R<21> are OH- protecting groups; Z<1> is OH, halogen, etc.,) is subjected to a reaction with a compound of formula III to provide the correspondent compound of formula I.

Description

Detailed Description of the Invention <Industrial Application Field> The present invention provides an acyl CoA-cholesterol acyltransferase (A cyl CoA-cholesteryltransferase).
erolA cyltransferase 1 or less “A
The present invention relates to a pantothenic acid derivative that has excellent inhibitory activity against CAT (abbreviated as "CAT").

<Prior art and problems> In recent years, in atherosclerosis, which is a common type of arteriosclerosis, fat deposits have been observed from the earliest stages of the onset of arteriosclerosis, and the main component of this accumulated fat is cholesterol; Furthermore, numerous histopathological and biochemical studies have revealed that this cholesterol is derived from plasma lipids.

Furthermore, various epidemiological studies have shown that hyperlipidemia is a major risk factor for arteriosclerotic diseases. Therefore, the treatment of hyperlipidemia has become increasingly important in terms of reducing the risk of arteriosclerotic disease, and therapeutic drugs for this purpose do not just lower serum lipid levels, but also improve serum lipid balance or improve arteriosclerosis. The emergence of a drug that can actively prevent the onset of sclerosis is desired.

Many drugs are already available for the treatment of hyperlipidemia, and although they have shown some degree of clinical efficacy in lowering total serum cholesterol, they are not necessarily sufficient in reducing mortality rates due to arteriosclerotic diseases. No effect has been recognized. In addition, in recent years, with the elucidation of 3 lipid metabolic systems, drugs that control serum lipid balance have been developed. or drugs that inhibit cholesterol biosynthesis and consequently lower serum lipid levels (HMG CoA reductase inh
ibitors) etc. are being developed. but,
Although these drugs are effective in improving blood lipid levels, they have little effect on controlling the absorption of dietary cholesterol from the intestinal wall, and furthermore, they do not actively prevent the onset or progression of arteriosclerosis. However, it remains to be determined whether or not it can reduce the risk of arteriosclerotic disease.

On the other hand, ACAT, which is known as an integral membrane enzyme, is present in large amounts in intracellular microsomes of the liver and small intestine, and controls the synthesis of cholesterol esters.

In addition, it is currently known that there are two types of isozymes in this enzyme, but their structures and their physiological roles have not yet been elucidated due to the difficulty in isolating and purifying this enzyme4. . However, ACAT is involved in the absorption of cholesterol between the intestines and its accumulation as cholesterol ester in cells, and its activity is known to be enhanced in arteriosclerotic lesions. It is expected to be useful as a drug that has both a blood lipid-lowering effect based on oral absorption inhibition and an anti-arteriosclerotic effect.

Therefore, the present inventors conducted intensive research to synthesize a substance having excellent ACAT inhibitory activity, and as a result, they have now completed the present invention.

<Disclosure of the Invention> According to the present invention, the following general formula RIO OR2? In the formula, R1 and R2 are the same or different and each represents a hydrogen atom or a hydroxyl group protecting group; R3 is saturated or unsaturated and optionally substituted with a linear, branched or cyclic aromatic group; Moyoi C5~
C25 represents a monovalent aliphatic hydrocarbon group or a group -NH-R4, where R' is saturated or unsaturated and optionally substituted with a linear, branched or cyclic aromatic group; represents a C5-C25 monovalent aliphatic hydrocarbon group; -N- represents a 4- to 7-membered divalent nitrogen-containing heterocyclic group bonded to the carbonyl group (CO), and R6 is a hydrogen atom or a lower alkyl group m is 0, 1 or 2; and n is an integer of 1 to 4. Compounds are provided.

In this specification, the term "lower" is used to indicate that the atomic group or compound modified with this term has 6 or less carbon atoms, preferably 4 or less carbon atoms.

Further, the "hydroxyl protecting group" can be any protecting group that can be removed by hydrolysis or hydrogenolysis, and examples thereof include those exemplified below. Methyl, methoxyethyl, methylthiomethyl, penzyloxymethyl, t-butoxymethyl, 2-methoxyethoxymethyl, 2.2.24 cycloethoxymethyl, bis(2-chloroethoxy)methyl, 1-ethoxyethyl, 1-methyl -1-methoxyethyl, 1(isobropoxy)ethyl, 2,2.2-trichloroethyl, t-butyl, allyl, cinnamyl, benzyl, p-methoxybenzyl, 0-nitrobenzyl, p-nitrobenzyl, p-
Substituted or unsubstituted alkyl or alkenyl groups such as chlorobenzyl, 0-chlorobenzyl, p-cyanobenzyl, diphenylmethyl, α-naphthyldiphenylmethyl, triphenylmethyl, di(p-methoxyphenyl)methyl; tetrahydride-pyranyl; Heterocyclic groups such as tetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydrothiofuranyl; trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, t -butyldiphenylsilyl, methyldiisobutylsilyl, methyldit-butylsilyl, tribenzylsilyl, triphenylsilyl,
Substituted silyl groups such as triisopropylsilyl; formyl,
Acetyl, propionyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, methoxyacetyl, triphenylmethoxyacetyl, phenoxyacetyl, p-chlorophenoxyacetyl, 2.
6 dichloro-4-methylphenoxyacetyl, phenylacetyl, chlorodiphenylacetyl, 3-phenylpropionyl, 3-penzoylpropionyl, isobutyroyl, monosuccinoyl, 4-8 oxopentanoyl, pivaloyl, 2-butenoyl, (
E)-2-methyl-2-butenoyl, benzoyl, 2-
Chlorobenzoyl, 3-nitrobenzoyl, 2-fluorobenzoyl, 3-trichlorobenzoyl, 3-trichlorobenzoyl, 4-phenylbenzoyl, 2.4.6-
Acyl groups such as 1-limethylbenzoyl and α-naphthoyl; methoxycarbonyl, ethoxycarbonyl, 2,2.
2-triethoxycarbonyl, isobutoxycarbonyl, vinyloxycarbonyl, aryloxycarbonyl, cinnamyloxycarbonyl, p-nitrophenoxycarbonyl, penzyloxycarbonyl, p-methoxybenzyloxycarbonyl, 34-dimethoxybenzyloxy Substituted oxycarponyl groups such as carbonyl, 0-nitropenzyloxycarbonyl, p-nitropenzyloxycarbonyl, phenylcarbamoyl, naphthylcarbamoyl, tolylcarbamoyl, fluorophenylcarbamoyl, difurophenylcarbamoyl, nitrophenylcarbamoyl, cyanophenylcarbamoyl, pendylcarbamoyl rucarbamoyl, methylcarbamoyl, ethylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, cyclohexylcarbamoyl, cyclopropylmethylcarbamoyl, phenylthiocarbamoyl, naphthylthiocarbamoyl, toluylthiocarbamoyl, fluorophenylthiocarbamoyl, difluorophenylthiocarbamoyl, Substituted carbamoyl groups such as nitrophenylthiocarbamoyl, cyanophenylthiocarbamoyl, pendylthiocarbamoyl, probylthiocarbamoyl, butylthiocarbamoyl, and the like.

In addition, in the above formula (1), when R+ and R2 represent a hydroxyl protecting group, Rl and R2 together,
methylene, ethylidene, 1-t-butylethylidene, 1
- phenylethylidene, 2. 2.2-Trichloroethylidene, isopropylidene, butylidene, cyclopentylidene, cyclohexylidene, cycloheptylidene,
Penzylidene, p-methoxybenzylidene, 2,4-dimethoxybenzylidene, p-dimethylaminobenzylidene, 0-nitrobenzylidene, methoxymethylene, ethoxymethylene, dimethoxymethylene, 1-methoxyethylidene, 1,2-dimethoxyethylidene, α-methoxybenzylidene It is also possible to form a ylidene group such as.

Examples of the saturated or unsaturated, linear, branched, or cyclic monovalent aliphatic hydrocarbon group j include the following.

(1) Alkyl group: For example, methyl, ethyl, proyl, isobrobyl, butyl, isobutyl, t-butyl, pentyl, neopentyl, isopentyl, t-pentyl, 1-ethylpentyl, 1-isobutylpentyl, 1-t-butyl Pentyl, 2-ethylbentyl, 2-isoprobylpentyl, 2-t-butylpentyl, 3-ethylpentyl, 3-isoprobylpentyl, 3-t-butylpentyl, hexyl, 1-ethylhexyl, 1-isopropylhexyl, 1 -t-butylhexyl, 2-ethylhexyl, 2-iso11 probylhexyl, 2-t-butylhexyl, 3-ethylhexyl, 3-isopropylhexyl, 3-t-butylhexyl, heptyl, 1-ethylheptyl, 1- Isopropylheptyl, 1-neobentylheptyl, 2-ethylheptyl, 2-isopropylheptyl, 2-neopentylheptyl, 3-ethylheptyl, 3-isobrobylheptyl, 3-neopentylheptyl, octyl, 1
-ethyl octyl, 1-isopropyroctyl, 1-t
1-butyloctyl, 2-ethyloctyl, 3-isopropyloctyl, 4-t-butyloctyl, nonyl, 1-
Methylnonyl, 1-ethylnonyl, 1-isopropylnonyl, 1-isobutylnonyl, 2-methylnonyl, 2-
Ethylnonyl, 3-isopropylnonyl, 4-isobutylnonyl, decyl, 1-ditylldecyl, 1,1-diethyldecyl, 1-1-butyldecyl, 3-ethyldecyl,
1.3-diethyl decyl, 2-t-butyl decyl, undecyl, 1-isopropyl undecyl, 1.1-diethyl undecyl, 2-isobrobyl undecyl, 1.2-diethyl undecyl, dodecyl, 1- 1-
butyldodecyl, 1-isobutyldodecyl, 1.1-
Diethyldodecyl, 2-t-butyldodecyl, 3-isoprobildodecyl, 2,4-diethyldodecyl, tridecyl, 1,1-diethyltridecyl, 1-t-butyltridecyl, 1,5-diethyltridecyl, 3-t- butyltridecyl, tetradecyl, 1-isobutyltetradecyl, pentadecyl, 1-methylpentadecyl, 1.1-
Dimethylpentadecyl, 1-ethylpentadecyl, 1.
1-diethylpentadecyl, 1-isobrobylpentadecyl, 1-t-butylpentadecyl, 2-isobutyltetrade, sil, 3-methylpentadecyl, 2.6-dimethylpentadecyl, 2-ethylpentadecyl, 1 .4-
Diethylpentadecyl, 3-isopropylpentadecyl, 2-t-butylpentadecyl, hexadecyl, 1.1
-dimethylhexadecyl, 1-methylhexadecyl, 1
-Ethylhexadecyl, 1-isopropylhexadecyl, 1-t-butylhexadecyl, 1,3-dimethylhexadecyl, 2-methylhexadecyl, 4-ethylhexadecyl, 3-isopropylhexadecyl, 4-t -butylhexadecyl, heptadecyl, 1-methylheptadecyl, 1.1 dimethylhebutadecyl, 1-ethylheptadecyl, 1-isobutylheptadecyl, 1-t-butylheptadecyl, 2-methylheptadecyl, 3.5 -dimethylheptadecyl, 2-ethylheptadecyl, 5-isopropylheptadecyl, 3-t-butylheptadecyl,
Octadecyl, ■-Methyloctadecyl, 1.1-dimethyloctadecyl, 1-ethyloctadecyl, 1.1-
Diethyl octadecyl, 2-methyl octadecyl, 2.
3-dimethyloctadecyl, 5-ethyloctadecyl,
1.2-diethyl octadecyl, nonadecyl, 1-methylnonadecyl, 1.1-dimethylnonadecyl, 1-t-butylnonadecyl, 2-methylnonadecyl, 2.3-dimethylnonadecyl, 3-t-butylnonadecyl, icosyl, 1-methylicosyl, 1.1-dimethylicosyl, 1
-ethyl icosyl, 1-t-butyl icosyl, 4-methyl icosyl, 2,2-dimethyl icosyl, 3-ethyl icosyl, 2-t-butyl icosyl, etc.

(2) Alkenyl groups: e.g. vinyl, 1-propenyl, 1-methyl-2-propenyl, 1-methyl-1-butenyl, 2-butenyl, 1-methyl-3-butenyl, 1-pentenyl, 1-methyl-2 −
Pentenyl, 1-ethyl-3-pentenyl, 4-pentenyl, 1,3-pentadienyl, 2.4-pentadienyl, 1-hexenyl, 1-methyl-2-hexenyl, 3
-hexenyl, 4-hexenyl, 1-butyl-5-hexenyl, 1,3-hexadienyl, 2,4-hexadienyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-hexenyl Putenyl, 5-hebutenyl, 6-heptenyl, 1,3-hebutadienyl, 2,4-heptadienyl,
1-octenyl, 2-octenyl, 3-octenyl, 4
-octenyl, 5-octenyl, 6-octenyl, 7-
Octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 415 1-nonenyl, 5-nonenyl, 6-nonenyl, 7-nonenyl, 8-nonenyl, 9-decenyl, 1-methyl-9-decenyl, 1.1- Dimethyl-9-decenyl, 1-ethyl-9-decenyl, 6-undecenyl, 1-methyl-6-
undecenyl, 1,1-dimethyl-6-undecenyl,
6-tridecenyl, 1-methyl-6-tridecenyl, 1
, 1-dimethyl-6-tridecenyl, 8-tridecenyl, 1-methyl-8-tridecenyl, 1,1-dimethyl-
8-tridecenyl, 10-tridecenyl, 1-methyl-1
0-tridecenyl, 1.1-dimethyl-10-tridecenyl, 10-pentadecenyl, 1-methyl-10-pentadecenyl, 1,1-dimethyl-10-pentadecenyl, 8-pentadecenyl, 1-methyl-8-pentadecenyl, 1. 1-dimethyl-8-pentadecenyl, 12-hebutadecenyl, 1-methyl-12-hebutadecenyl, 1
, 1-dimethyl-12-heptadecenyl, 10-hebutadecenyl, 1-methyl-10-heptadecenyl, 1.1
-dimethyl-10-heptadecenyl, 8-heptadecenyl, 1-methyl-8-hebutadecenyl, 1,1-dimethyl-8-heptadecenyl, 1-ethyl-8-heptadecenyl, 8,11-heptadecadienyl, 1 -Methyl-8,11-butadienyl, 8
, 11.14-heptadecatrienyl and the like.

(3) Alkynyl group: e.g. propargyl, 2-butynyl, 1-methyl-3-butynyl, 2-pentynyl, 1-ethyl-3-pentynyl, 1-
Isoprobyl-4-pentynyl, 1.3-pentadiynyl, 2.4-pentadiynyl, 1-hexynyl, 1-methyl-2-hexynyl, 2-methyl-3-hexynyl,
1-ethyl-4hexynyl, 5-hexynyl, 1.3-
Hexadiynyl, 2.4-hexadiynyl, 1-hebutynyl, 1-methyl-2-heptynyl, 3-heptynyl,
1-ethyl-4-hebutynyl, 2-propyl-5-hebutynyl, 2-ethyl-6-heptynyl, 1.3-heptadiynyl, 2.4-hebutynyl, 1-octynyl,
1-methyl-2-octynyl, 3-methyl-1-octynyl, 4-methyl-1-octynyl, 1-methyl-5-
Octynyl, 6-methyl-1-octynyl, 7-octynyl, 1-nonynyl, 2-methyl-1-nonynyl, 3-
Methyl-1-nonynyl, 1-methyl-4-nonynyl, 5
-nonynyl, 6-methyl-1-nonynyl, 1-methyl-
7-nonynyl, 8-nonynyl, 9-decynyl, 1-methyl-9-decynyl, 1,1-dimethyl-9-decynyl,
1-ethyl-9-decynyl, 6-undecynyl, 1-methyl-6-undecynyl, 1,1-dimethyl-6-undecynyl, 6-tridecynyl, 1-methyl-6-tridecynyl, 1,1-dimethyl-6- Tridecynyl, 8-tridecynyl, 1-methyl-8-tridecynyl, 1.1-
Dimethyl-8-tridecynyl, 10-tridecynyl, 1
-Methyl-10-tridecynyl, 1,1-dimethyl-1
0-tridecynyl, 10-pentadecynyl, 1-methyl-10-pentadecynyl, 1.1-dimethyl-10-pentadecynyl, 8-pentadecynyl, 1-methyl-8-
Pentadeshell, 1,1-dimethyl-8-pentadecynyl, 12-heptadecinyl, 1-methyl-12-heptadecinyl, 1,1-dimethyl-12-heptadecinyl,
10-heptadecinyl, 1-methyl-10-heptadecinyl, 1.1-dimethyl-10heptadecinyl, 8-heptadecinyl, 1-methyl-8-heptadecinyl, 1.
1-dimethyl-8-heptadecinyl, 1-ethyl-8-heptadecinyl, . 8.11-Hebutadecadiynyl, 1-
Methyl-8,11-hebutadecadiynyl, 8,11
．． 14-hebutadecatriynyl and the like.

(4) Cycloalkyl group: for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, perhydronaphthyl, etc.

(5) Cycloalkenyl group: for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclopentakienyl, cyclohexadienyl, cyclohebutadienyl, cyclooctadienyl, etc.

19 (6) Cycloalkylalkyl group: For example, cyclohexylmethyl, cyclobentylmethyl, (4-isopropylcyclohexyl)methyl, (4t-butylcyclohexyl)methyl, (4-neopanthylcyclohexyl)methyl, 2-cyclopentylethyl, 2 -Cyclohexylethyl, 3-cyclopentylpropyl, 3-cyclohexylpropyl, 1-cyclobentylpentyl, 1-cyclohexylpentyl, 1-cyclohexylmethylpentyl, 3-cyclopentylpentyl, 2cyclohexylpentyl, 2-cyclohexylmethyl Pentyl, 1-(4-
t-butylcyclohexyl) methylpentyl, 1-cyclopentylhexyl, 1-cyclohexylhexyl, 1
-Cyclopentylmethylhexyl, 2-cyclopentylhexyl, 2-cyclohexylhexyl, 3-cyclopentylmethylhexyl, 1-(4-neopentylcyclohexyl)methylhexyl, 1-cyclopentylheptyl, 1-cyclohexylmethylheptyl, 1-(4 -isoprobylcyclohexyl20) methylheptyl, 3-cyclopentylheptyl, 2
-Cyclohexylmethylhebutyl, 4(4-isoprobylcyclohexyl)methylheptyl, 1-cyclopentyloctyl, 1-cyclohexyloctyl, 1-cyclopentylmethyloctyl, 2-cyclopentyloctyl, 3-cyclohexyloctyl, 2-cyclopentyl Methyloctyl, 1-cyclopentylnonyl, ■-cyclohexylnonyl, 1-cyclohexylmethylnonyl, 3
-cyclopentylnonyl, 2-cyclohexylnonyl,
2-cyclohexylmethylnonyl, 1-cyclopentyldecyl, 1-cyclopentylundecyl, 1-cyclohexylundecyl, 1-cyclopentyldodecyl, 1-cyclopentyltridecyl, 2-cyclopentyldecyl,
3-cyclopentylundecyl, 3-cyclohexylundecyl, 2-cyclopentyldodecyl, 2-cyclopentyltridecyl, 1-cyclopentyltetradecyl,
1-cyclohexyltetradecyl, 2-cyclopentyltetradecyl, 3-cyclohexyltetradecyl, etc.

(7) Cycloalkenylalkyl group: e.g. 2-cyclohexen-1-ylmethyl, 1-cyclobentene-1-
ylmethyl, 2-(2-cyclopenten-1-yl)
Ethyl, 2-(1-cyclohexen-1-yl)ethyl, 3-(1-cyclopenten-1-yl)propyl, 3-(1-cyclohexen-1-yl)propyl,
4-(1-cyclohexen-1-yl)butyl, 1-
(1-cyclopenten-1-yl)pentyl, 5-(
1cyclopenten-1-yl)pentyl, l. -Hcyclohexen-1-yl)pentyl, 5-(1cyclohexen-1-yl)pentyl, 1-(1-cyclohexen-1-ylmethyl)pentyl, 1-(1-cyclohexen-1-yl)hexyl, 6-(1-penten-1-yl)hexyl, 1-(1-penten-1-yl)
1-yl)hexyl, 6-(1-cyclohexene-1-
yl)hexyl, 1-(2-cyclopenten-1-ylmethyl)hexyl, 1-(1-cyclopenten-1-yl)heptyl, 7-(1-cyclopenten-1-yl)
Heptyl, 1-(1-cyclohexen-1-ylmethyl)heptyl, 1-(1-cyclopenten-1-yl)octyl, 1-(2-cyclopenten-1-yl)octyl,
1-(2-cyclohexen-1-yl)octyl, 8-
(2-cyclohexen-1-yl)octyl, 1-(
1-penten-1-ylmethyl)octyl, 1-
(1-cyclopenten-1-yl)nonyl, 9-(1cyclopenten-1-yl)nonyl, 1-(1-cyclohexen-1-yl)nonyl, 9-(1cyclohexen-1-yl)nonyl, 1-( 1-cyclohexene-1-
ylmethyl)nonyl, 1-(1-cyclopentene-1-
yl) decyl, 10(1-penten-1-yl)
Decyl, 1(2-cyclopenten-1-yl)undecyl, 1-(2-cyclohexen-1-yl)undecyl, 1-(1-cyclopenten-1-yl)dodecyl,
1-(1-cyclopenten-1-yl)tridecyl, 1
-(2-cyclopenten-1-yl)23 Tetradecyl, 1-(3-cyclohexen-1-yl)
such as tetradecyl.

(8) Alkylcycloalkyl group and alkenylcycloalkyl group: e.g. 1-methylcyclobutyl, 2-ethylcyclobutyl, 2
-propylcyclobutyl, 1-butylcyclobutyl, 1
-pentylcyclobutyl, 1-hexylcyclobutyl,
1-heptylcyclobutyl, 1-octylcyclobutyl, 1-nonylcyclobutyl, 2-pentylcyclobutyl, 2-hexylcyclobutyl, 2-heptylcyclobutyl, 2-octylcyclobutyl, 2-nonylcyclobutyl , 1-decylcyclobutyl, 1-undecylcyclobutyl, 1-dodecylcyclobutyl, 1-pentadecylcyclobutyl, 1-(9-octadecenyl)cyclobutyl, 1-methylcyclopentyl, 2-methylcyclopentyl, 1-ethyl Cyclobentyl, 1-propylcyclopentyl, 1-butylcyclopentyl, 2-butylcyclopentyl, 1-pentylcyclopentyl, 1-hexylcyclopentyl, 3-hexylcyclopentyl, 1-heptylcyclopentyl, 1-octylcyclopentyl Pentyl, 2-octylcyclopentyl, 1-decylcyclopentyl, 1-
dodecylpentyl, 1 tridecylpentyl, 1-tetradecylpentyl, 1-(9-octadecenyl)cyclopentyl, 1-methylcyclohexyl, 1ethylcyclohexyl, 1-propylcyclohexyl, 2-methylcyclohexyl, 3- Ethylcyclohexyl, 4-propylcyclohexyl, 1-butylcyclohexyl, 1-pentylcyclohexyl, 1-hexylcyclohexyl, 4-butylcyclohexyl, 4-pentylcyclohexyl, 4-hexylcyclohexyl, 1-heptylcyclohexyl, 1-octyl hexyl,
1-nonylcyclohexyl, 1-undecylcyclohexyl, 1-hexadecylcyclohexyl, 1(9-octadecenyl)cyclohexyl, etc.

(9) Alkylcycloalkenyl groups and alkenylcycloalkenyl groups: e.g. 1-methyl-2-cyclopentenyl, 1-ethyl-2-cyclopentenyl, 1-propyl-2-cyclopentenyl, 1-butyl-2-cyclopentenyl, 1 -pentyl-2-cyclopentenyl, 1-hexyl-2-cyclopentenyl, 1-heptyl-2-cyclopentenyl, 1-octyl-2-cyclopentenyl, 2-methyl-2-cyclopentenyl, 3-ethyl-2- Cyclopentenyl, 2-brobyl-3-cyclopentenyl, 3-butyl-2-cyclopentenyl, 2-pentyl-2-cyclopentenyl, 3
-hexyl-3-cyclopentenyl, 2-heptyl-
2-cyclopenotenyl, 2-octyl-3-cyclopentenyl, 1-decyl-2-cyclopentenyl, 1-dodecyl-2-cyclopentenyl, 1-tridecyl-2-cyclopentenyl, 1-tetradecyl-2-cyclopentenyl, 1-(9 -octadecenyl)-2-cyclopentenyl, 1-methyl-2-cyclohexenyl, 1-ethyl-
2-cyclohexenyl, 1-propyl-2-cyclohexenyl, 1-butyl-2-cyclohexenyl, 1-pentyl-2-cyclohexenyl, 1-hexyl-2-cyclohexenyl, 1-heptyl-2-cyclo hexenyl, 4methyl-2-cyclohexenyl, 2-ethyl-2-
Cyclohexenyl, 3-propyl-2-cyclohexenyl, 4-butyl-3-cyclohexenyl, 3-pentyl-3-cyclohexenyl, 4-hexyl-3-cyclohexenyl, 4-heptyl-3- cyclohexenyl, 1-
Octyl-2-cyclohexenyl, 1-nonyl-2-cyclohexenyl, 1-undecyl-2-cyclohexenyl, 1-hexadecyl-2-cyclohexenyl, 1-(
9-octadecenyl)-2-cyclohexenyl, etc.

The "aromatic group" in "a saturated or unsaturated monovalent aliphatic hydrocarbon group optionally substituted with a linear, branched, or cyclic aromatic group" includes, for example, phenyl, naphthyl, Aromatic hydrocarbon groups such as furyl, chenyl, pyridyl, quinolyl, isoquinolyl, pyridazinyl, pyrazonyl, 27 indolyl, penzoxadiazolyl, imidazolyl,
Aromatic heterocyclic groups such as penzothiazolyl, triazolyl, and tetrazolyl are included. These aromatic groups may be further substituted, and examples of the substituent include halogen atoms such as chlorine atom, bromine atom, and fluorine atom, lower alkyl group, lower alkoxy group, cyano group, nitro group, trichloromethyl group, etc. Examples include groups such as a trifluoromethyl group, a hydroxy group, a phenyl group, a phenoxy group, and a lower alkylthio group.

The saturated aliphatic hydrocarbon group represented by R3 in the above general formula is an unsaturated monovalent aliphatic hydrocarbon group optionally substituted with a linear, branched or cyclic aromatic group; Among these, those having relatively long chains, ie, those having 5 to 25 carbon atoms, preferably 8 to 22 carbon atoms, are suitable.

Specific examples of the group -NH-R4 that can be represented by R3 in the general formula (I) include, for example, 2-
Cyclopentylethylamino, 2-cyclohexylethylamino, 3-cyclopenty28 Rubrobylamino, 3-cyclohexylbropylamino, 2-cyclopentyl-1-methylethylamino, 2-
cyclopentyl-1,1-dimethylethylamino, 2-
Cyclohexyl-1-methylethylamino, 3-cyclopentylpropylamino, 3-cyclohexylpropylamino, 4-cyclohexyl-1.1-dimethylbutylamino, 1-methylpentylamino, 1.1-dimethylpentyl Amino, 1-ethylpentylamino, 1-cyclohexyl-4-methylpentylamino, 1-cyclopentyl-4-methylpentylamino, 2-methylpentylamino, 1,2-dimethylpentylamino, 2-ethylpentylamino, 2 1-cyclohexyl-4-methylpentylamino, 2-cyclohexyl-4-methylpentylamino, 3-methylpentylamino, 1,3-dimethylpentylamino, 3-ethylpentylamino, 1-cyclohexyl-3-methyl pentylamino, 1-cyclobentylamino, 3-methylpentylamino, hexylamino,
1-methylhexylamino, 1,1-dimethylhexylamino, 1-ethylhexylamino, 1,1-diethylhexylamino, 1-bropyhexylamino, 1-butylhexylamino, 1-cyclopentylhexylamino, 2-methylhexylamino, 1,2-dimethylhexylamino, 2-ethylhexylamino, 1,2-diethylhexylamino, 2-probylhexylamino, 2-
butylhexylamino, 6-cyclobentyhexylamino, 6-cyclohexylhexylamino, heptylamino, 1-ethylheptylamino, 1.1-dimethylheptylamino, 1-cyclohexylheptylamino, 1
-cyclopentylheptylamino, 1-cyclohexylmethylheptylamino, 1-cyclopentylmethylheptylamino, octylamino, 1.1-dimethyloctylamino, 1-methyloctylamino, 1-ethyloctylamino, 1.1-diethyloctylamino, 1-propyloctylamino, 1-butyloctylamino, 1
-Cyclopentyloctylamino, 1-cyclohexyloctylamino, 1-cyclopentylmethyloctylamino, 1-cyclohexylmethyloctylamino, nonylamino, 1-methylnonylamino, 1.1-dimethylnonylamino, 1-ethylnonylamino, 1 .1-diethylnonylamino, decylamino, 1-methyldecylamino, 1.1-dimethyldecylamino, 1-ditylldecylamino, 1.1-diethyldecylamino, 1-cyclopentyldecylamino, 1-cyclohexyldecyl Amino, 1-cyclopentylmethyldecylamino, 1-cyclohexylmethyldecylamino, undecylamino, 1
-Methylundecylamino, 1,1-dimethylundecylamino, dodecylamino, 1-methyldodecylamino, 1,1-dimethyldodecylamino, tetradecylamino, 1-methyltetradecylamino, 1,1-dimethyltetradecyl Amino, pentadecylamino, 1-methylpentadecylamino, 1,1-dimethylpentadecylamino, hexadecylamino, 1-methylhexadecylamino, 1,1-dimethylhexadecylamino, hep31 tadecylamino, 1-methylhexadecylamino Butadecylamino, 1.
1-dimethylheptadecylamino, octadecylamino, 1-methyloctadecylamino, 1.1-dimethyloctadecylamino, 3-cyclopentyl-2-probenylamino, 3-cyclohexyl-2-propenylamino, 1.1-dimethyl-3 -butenylamino, 1-ethyl-3-butenylamino, 1-cyclopropyl-3-butenylamino, 1-methyl-2-pentenylamino, 1.
1-dimethyl-2-pentenylamino, 1-ethyl-2
-Pentenylamino, 1-propyl 2-pentenylamino, 2-hexenylamino, 1-methyl-2-hexenylamino, 1,1-dimethyl-2-hexenylamino, 3-hexenylamino, 1-methyl-3- hexenylamino, 1.1-dimethyl-3-hexenylamino, 2-heptenylamino, 1-methyl-2-heptenylamino, 2-octenylamino, 1-methyl-2-octenylamino, 3-nonenylamino, 1-methyl- 3-nonenylamino, 1,1-dimethyl-332-1-nonenylamino, 1-ethyl-3-nonenylamino,
1-propyl-3-nonenylamino, 8-nonenylamino, 1-methyl-8-nonenylamino, 1,1-dimethyl-8-nonenylamino, 1-ethyl-8-nonenylamino, 9-decenylamino, 1-methyl-9-decenylamino, 1 .1=dimethyl-9-decenylamino, 1-ethyl 9-decenylamino, 6-undecenylamino, 1
-Methyl-6-undecenylamino, 1. 1-dimethyl-6-undecenylamino, 6-tridecenylamino, 1-methyl-6-tridecenylamino, 1.1-dimethyl-6-tridecenylamino, 8-tridecenylamino, 1 -Methyl-8-tridecenylamino, 1.1-dimethyl-8-tridecenylamino, 10-tridecenylamino, 1-methyl-10-tridecenylamino, 1.
1 dimethyl-10-tridecenylamino, 101 pentadecenylamino, 1-methyl-10-pentadecenylamino, 1.1-dimethyl-10-pentadecenylamino, 8-pentadecenylamino nylamino, 1-methyl-8-pentadecenylamino, 1,1-dimethyl-8-pentadecenylamino, 12-hebutadecenylamino, 1-methyl-
12-heptadecenylamino, 1,1-dimethyl-12
-hebutadecenylamino, 10-hebutadecenylamino, 1-methyl-10-hebutadecenylamino, 1.1-
Dimethyl-10-hebutadecenylamino, 8-hebutadecenylamino, 1-methyl-8-hebutadecenylamino, 1.1-dimethyl-8-hebutadecenylamino, 1-
Ethyl-8-hebutadecenylamino, 8.11-heptadecadienylamino, 1-methyl-8.11-hebutadecadienylamino, 8,11.14-hebutadecatrienylamino, 1 -Ethylcyclobutylamino, 1-propylcyclobutylamino, 1-butylcyclobutylamino, 1-pentylcyclobutylamino, 1-hexylcyclobutylamino, 1-pentylcyclobutylamino,
1-octylcyclobutylamino, 1-nonylbutylamino, 1-decylcyclobutylamino, 1-undecylcyclobutylamino, 1-dodecylcyclobutylamino, 1-pentadecylcyclobutylamino, 1-
(9-octadecenyl)cycloptylamino, 1-methylcyclopentylamino, 1-ethylcyclopentylamino, 1-propylcyclopentylamino, 1-butylcyclopentylamino, 1-hexylcyclopentylamino, 1-octylcyclopentylamino, 1- Decylpentylamino, 1-dodecylpentylamino, 1-tridecylpentylamino, 1-tetradecylpentylamino, 1-(9-octadecenyl)cyclopentylamino, cyclohexylamino, 1
-Methylcyclohexylamino, 1-propylcyclohexylamino, 1-pentylcyclohexylamino, 1
-heptyl hexylamino, 1-nonyl hexylamino, 1 undecyl hexylamino, 1
Monosubstituted amino groups such as -hexadecylcyclohexylamino, 1-(9-octadecenyl)cyclohexylamino; 1-penzylhexylamino, 1-penzyl35
1-heptylamino, 1-penzyloctylamino, 1-penzylnonylamino, 1-penzyldecylamino, 1-
Penzylundecylamino, 1-penzyldodecylamino, 1-penzyltetradecylamino, 1-penzylhexadecylamino, 1-phenyldecylamino, 1-benzyl-8-heptadecenylamino groups are mentioned. It will be done.

Preferably, 5- or 6-membered divalent nitrogen-containing heterocyclic groups are included, and when X represents these nitrogen-containing heterocyclic groups,
When the nitrogen atom in the group is bonded to the carbonyl group on the left side in formula (I), and Y represents the above-mentioned dicontaining heterocyclic group, the nitrogen atom in the group is bonded to the carbonyl group on the left side in formula (I). Can be bonded to a carbonyl group. X represents the above nitrogen-containing heterocyclic group.

Among the compounds provided by the present invention, preferable ones include, in the general formula (I), R1 and R2 are the same or different, and each is a hydrogen atom; a lower alkyl group, especially a t-butyl group; benzyl groups optionally substituted with atoms, lower alkoxy groups, nitro groups or cyano groups, in particular benzyl, p-methoxybenzyl, O-nitrobenzyl, p-nitrobenzyl, p-chlorobenzyl, O-chlorobenzyl, p -cyanobenzyl group; diphenylmethyl group; allyl group: cinnamyl group; tetrahydropyranyl, tetrahydrothiopyranyl, 4
- a heterocyclic group selected from methoxytetrahydrode-pyranyl, 4-methoxytetrahydride-hythiopyranyl, tetrahydride-furanyl and tetrahydride-thiofuranyl; or an acyl group, especially acetyl, propionyl, phenylacetyl, chlorodiphenylacetyl, 3-phenylbu-pionyl, 3-penzoyl-butyroyl, isobutyroyl, bivaloyl, 2-butenoyl, (E)-2-methyl-2-butenoyl, benzoyl, 2-chlorobenzoyl, 3-nitrobenzoyl, 2-phlorobenzoyl, 3 −
represents trifluoromethylbenzoyl, 3-trichloromethylbenzoyl, 4-phenylbenzoyl, 2.4.6-trimethylbenzoyl, α-naphthoyl, or R1 and R2 together represent 1-t-butylethylidene,
selected from 1-phenylethylidene, isopropylidene, butylidene, cyclopentylidene, cyclohexylidene, cycloheptylidene, penzylidene, p-methoxybenzylidene, 2,4-dimethoxybenzylidene, p-dimethylaminobenzylidene and O-nitropenzylidene represents a ylidene group, and R3 is (1) C, which is linear or has a branched chain at the 1-position, ~C2
5 alkyl groups, especially pentyl, 1-isobutylpentyl, 1-t-butylpentyl, hexyl, 1-isobutylhexyl, 1-t-butylhexyl, heptyl,
1-isopropylheptyl, 1-t-butylheptyl,
Octyl, 1-t-butyloctyl, nonyl, 1-isobutylnonyl, decyl, 1-ethyldecyl, 1.1-diethyldecyl, 1-t-butyldecyl, undecyl, 1
-isopropylundecyl, 1,1-diethylundecyl, dodecyl, 1-t-butyldodecyl, 1-isopropyldodecyl, 1,1-diethyldodecyl, tridecyl, 1,1-diethyltridecyl, 1-t-butyltridecyl , tetradecyl, 1-isobutyltetradecyl, pentadecyl, 1-methylpentadecyl, 1.1-dimethylpentadecyl, 1-ethylpentadecyl, 1.1-diethylpentadecyl, 1-isopropylpentadecyl, 1
-t-butylpentadecyl, hexadecyl, 1,1-dimethylhexadecyl, 1-methylhexadecyl, 1-ethylhexadecyl, 1-isobutylhexadecyl, 1
-t-butylhexadecyl, heptadecyl, 1-methylhebutadecyl, 1.1-
Dimethylheptadecyl, 1-ethylhebutadecyl, 1-
Isopropylheptadecyl, 1-t-butylheptadecyl, octadecyl, 1-methyloctadecyl, 1.1-
Dimethyl octadecyl, 1-ethyl octadecyl or 1,1-diethyl octadecyl group; (2) straight chain, if << means CI2-C having a branched chain at the 1-position
l8 alkenyl groups, especially 1,1-dimethyl-9-decenyl, 1-ethyl-9-decenyl, 1-methyl-6-undecenyl, 1,1-dimethyl-6-undecenyl, 6-tridecenyl, 1-methyl-6- Tridecenyl, 1,1-
Dimethyl-6-tridecenyl, 8-tridecenyl, 1-methyl-8-tridecenyl, 1.1-dimethyl-8-tridecenyl, 10-tridecenyl, 1-methyl-10-tridecenyl, 1.1-dimethyl-10-tridecenyl,
10-pentadecenyl, 1-methyl-10-pentadecenyl, 1.1-dimethyl-10-pentadecenyl, 8-
Pentadecenyl, 1-40 Methyl-8-pentadecenyl, 1.1-dimethyl 8-pentadecenyl, 12-hebutadecenyl, 1-methyl-1
2-hebutadecenyl, 1.1-dimethyl-12-hebutadecenyl, 10-hebutadecenyl, 1-methyl-10-
Heptadecenyl, 1.1-dimethyl-10-heptadecenyl, 8-hebutadecenyl, 1-methyl-8-heptadecenyl, 1.1-dimethyl-8-heptadecenyl, 1-
Ethyl-8-heptadecenyl, 8.11-hebutadecadienyl, 1-methyl-8.11-hebutadecadienyl or 8,11.14-heptadecatrienyl group: (3) C8-CI8-alkyl-C4-C6 cycloalkyl group , especially 1-octylcyclobutyl, 1nonylcyclobutyl, 1-decylcyclobutyl, 1-undecylcyclobutyl, 1-dodecylcyclobutyl, 1-pentadecylcyclobutyl, 1(9-octadecenyl)cyclobutyl, 1- Octylbentyl, 1-decylpentyl, 1-dodecylpentyl, 1-tridecylcyclopentyl, 1-tetradecylcyclopentyl, 1-(9-octadecenyl)cyclopentyl, 1-nonylcyclohexyl, 1-undecylcyclohexyl, 1
-hexadecylcyclohexyl or 1-(9-octadecenyl)cyclohexyl group; or (4) an amino group monosubstituted with an alkyl group or alkenyl group having 8 to 20 carbon atoms, such as 1-isopropylpentylamino, 1-t -Butylpentylamino, 1-isoprobylhexylamino, 1-1-butylhexylamino, 1-isoprobylhexylamino, 1-t-butylheptylamino, 1-t-butyloctylamino, 1-
Isobutylnonylamino, Decylamino, 1-ethyldecylamino, 1,1-diethyldecylamino, 1-t-butyldecylamino, undecylamino, 1-isopropyl undecylamino, 1,1-diethyl undecylamino, dodecylamino , 1-t-butyldodecylamino,
1-isobutyltridecylamino, 1.1-diethyldodecylamino, tridecylamino, 1.1-dietyltridecylamino, 1-t-butyltridecylamino, tetradecylamino, 1-isobutyltetradecylamino, Pentadecylamino, 1-methylpentadecylamino, 1.1-dimethylpentadecylamino, 1-ethylpentadecylamino, 1.1-jetylpentadecylamino, 1-isoprobylpentadecylamino, 1-t-butyl Pentadecylamino, hexadecylamino, 1.1
-dimethylhexadecylamino, 1-methylhexadecylamino, 1-ethylhexadecylamino, 1-isobutylhexadecylamino, 1-t-butylhexadecylamino, heptadecylamino, 1-methylheptadecylamino, 1 .1-dimethylheptadecylamino, ■-
Ethylheptadecylamino, ■-isopropylhebutadecylamino, 1-t-butylhebutadecylamino, octadecylamino, 1methyloctadecylamino, 1.1
-dimethyloctadecylamino, 1-ethyloctadecylamino, 1.1-diethyloctadecylamino, 1,
43 Agemethyl-9-decenylamino, 1-ethyl-9-
Decenylamino, 1-methyl-6-undecenylamino, 1,1-dimethyl-6-undecenylamino, 1-methyl-6-tridecenylamino, 1,1-dimethyl-6
-tridecenylamino, 8-tridecenylamino, 1-
Methyl-8-tridecenylamino, 1,1-dimethyl-
8-tridecenylamino, 10-tridecenylamino,
1-methyl-10-tridecenylamino, 1.1-dimethyl-10-tridecenylamino, 10-pentadecenylamino, 1-methyl-10-pentadecenylamino, 1
, 1-dimethyl-10-pentadecenylamino, 8-pentadecenylamino, 1-methyl-8-pentadecenylamino, 1.1-dimethyl-8-pentadecenylamino, 12-to Butadecenylamino, 1-methyl-12-heptadecenylamino, 1,1-dimethyl-12-hebutadecenylamino, 10-hebutadecenylamino, 1-methyl-10-hebutylamino Decenylamino, 1,1-dimethyl-10-hebutadecenylamino, 8-44 Heptadecenylamino, 1-methyl-8-hebutadecenylamino, 1,1-dimethyl-8- Hebutadecenylamino, 1-ethyl-8-hebutadecenylamino, 8.11
-heptadecadienylamino, 1-methyl-8,11-
Hebutadecadienylamino, 8.11.14-Hebutadecatrienylamino, 1-hexylcyclobutylamino, 1-heptylcyclobutylamino, 1-octylcyclobutylamino, 1-nonylcyclobutylamino, 1-decylcycloptyl Amino, 1-undecylcyclobutylamino, 1-dodecylcyclobutylamino, 1-pentadecylcyclobutylamino, 1(9-octadecenyl)
Cycloptylamino, 1-pentylcyclobentylamino, 1-hexylpentylamino, 1-heptylcyclopentylamino, 1-octylpentylamino, 1-decylcyclopentylamino, 1-dodecylpentylamino, 1 -tridecylpentylamino, 1-tetradecylpentylamino, 1-
(9-octadecenyl)cyclopentylamino, 1-nonylcyclohexylamino, 1-undecylcyclohexylamino, 1 hexadecylcyclohexylamino, 1
- (9-octadecenyl)cyclohexylamino, 1
-penzylhexylamino, 1-penzylheptylamino, 1-penzyloctylamino, 1-penzylnonylamino, 1-benzyldecylamino, 1-penzylundecylamino, 1-penzyldodecylamino, 1-penzyl Tetradecylamino, 1-penzylhexadecylamino, 1-phenyldecylamino, 1-benzyl-8-
and the other is -O- -S- -NH- -N- m is 0, 1 or 2, and n is an integer from 1 to 4. It will be done.

Thus, representative examples of the compound represented by the general formula (I) provided by the present invention are as follows.

・2-octanoylnoylaminomethyl-1-[3N-
(2,2.5.5-tetramethyl-1.3dioxane-4-carbonyl)amino]propanoyl]pinolysine 2-decanoylaminomethyl-1-[3-N(2,2
,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propanoylcopi-lysine 2-tetradecanoylaminomethyl-1-[3-N-
(2,2.5.5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propanoyl]pinolysine 2-hexadecanoylaminomethyl-1-[3N-
(2,2.5.5-tetramethyl-1,3dioxane-4-carbonyl)amino]propanoyl]pyrrolidine 2-octadecanoylaminomethyl-1-[3-N-
(2.2.5.5-tetramethyl-1.3-dioxane-4-carbonyl)amino]propanoyl]pyrrolidine 2-(7-decenoyl)aminomethyl-1-[3N
- (2.2.5.5-tetramethyl-1.3-dioxane-4-carbonyl)amino]propanoyl]pyrrolidine 2-(9-}lidecenoyl)aminomethyl-1-
[3-N- (2,2,5.5-tetramethyl-1,3
-dioxane-4-carponyl)amino]propanoyl]pinolysine 2-(9-year-old tadecenoyl)aminomethyl-1
[3-N-(2.2.5.5-tetramethyl1,
3-Dioxane-4-carboni)amino]propanoyl]virolidine 2-(9,12-octadecajenoyl)aminomethyl-1-[3-N-(2.2,5.5-tetramethyl-1. 3-dioxane-4-carbo48yl)amino]propanoyl]pisolysine 2-(
9,12.15-octadetrienoyl)aminomethyl-1-[3-N-(2,2.5.5-tetramethyl-1,3-dioxane-4-carbonyl)amino]
[propanoyl] pisolysine 2-(2,2-methyl-9
-octadecenoyl)aminomethyl-1- [3-N
- (2,2.5.5tetramethyl-1.3-dioxane-4-carbonyl)amino]probanoylcopi-lysine 2-(2,2-dimethyl-9-octadecenoyl)aminomethyl-1- [3-N - (2.2.5
．． 5-Tetramethyl-1,3-dioxane-4-carbonyl)amino]propanoyl]pinolysine 2-(2-methyldecanoyl)aminomethyl 1 [
3-N- (2,2.5.5-tetramethyl-1.3-
dioxane-4-carbonyl)amino J-propanoyl]
Pyrrolidine (2-methyloctanoyl)aminomethyl 1 [3-
N-2.2,5.5-tetramethyl・21.3-dioxane-4-carbonyl)aminocopropanoyl]picolysine・2-(2-methylundecanoyl)aminomethyl-
1-[3-N-2.2.5.5-tetramethyl-1.
3-Dioxane-4-carbonyl)amino]propanoyl]pyrrolidine 2-(9-octadecenoyl)aminomethyl-1-
[3-N-(2.4-dihydroxy-3.3-dimethyl-1-oxobutyl)aminocopropanoyl]pyrrolidine 3-(9-ocitadecenoyl)amino-A [3-N
- (2,2.5.5-tetramethyl-1.3dioxane-4-carponyl)amino]propanoyl]piperidine 3-(9-octadecenoyl)amino-1-[3-N
- (2,4-dihydroxy-3,3-dimethyl-1-
Oxobutyl)amino]propanoyl]piperidine 1-(9-octadecenoyl)-3-[3-N
- (2.4-dihydroxy-3.3-dimethyl 1-oxobutyl)amino]propanoyl]aminopiperidine 1-(9-octadecenoyl)-3- [3-[
N-(2,2.5.5-tetramethyl-1.3-dioxane-4-carponyl)aminopanoyl]aminopiperidine 1-(9-octadecenoyl)-4- [3-N
(2,2,5.5-tetramethyl-1,3-dioxane-4-carbonylamino)propanoyl]aminopiperidine 1-(9-octadecenoyl)-4-piperidinyl 3-[N- (2.2,5 .5-Tetramethyl-1,3-dioxane-4-carbonyl)aminocopropionate 1-(9-octadecenoyl)-4-piperidinyl 3-[N-(2,4-dihydroxy-3.3-
Dimethyl-1-oxobutylamino]propionate 1-(9-octadecenoyl)-3-piperidinyl 3 [N-(2,2,5.5-tetramethyl51 1.3-dioxane-4-carponyl)amino]propionate・1-(9-octadecenoyl)-4-piperidinyl 3-[N-(2,4-diacetoxy3,3-dimethyl-1-oxobutyl)aminocobropionate ・1-(9-octadecenoyl)-3-piperidinyl 3- [N- (2.4-dihydroxy-3.3-dimethyl-1-oxobutyl)amino]propionate 1- (9-octadecenoyl)-3-piperidinyl 3- [N- (2.4-diacetoxy3. 3-dimethyl-1-oxobutyl)amino]propionate 1-(9-octadecenoyl)2-pyrrolidinylmethyl 3-[N-(2,2,5.5-tetramethyl-1,3-dioxane-4- carponyl)amino]propionate 1-octadecanoyl-2-pyrrolidinylmethyl 3
- [N- (2.2,5.5-tetramethyl52 1,3-dioxane-4-carbonyl)aminocopropionate 1-(9.12-octadecadienoyl)-2pyrrolidinylmethyl 3 - [N- (2,2,5.5-tetrametry 1,3-dioxane-4carbonyl)amino]propionate 1- (9-octadecenoyl)-2-pyrrolidinylmethyl 3- [N- (2. 4-dihydroxy3.
3-dimethyl-1-oxobutyl)aminocopropionate 1-(9-octadecenoyl)-2-pyrrolidinylmethyl 3-[N-(2.4-diacetoxy-3.
3-dimethyl-1-oxobutyl)amino]propionate 1-(9-octadecenoyl)-2-[3-[
N(2,2,5.5-tetramethyl-1.3-dioxane-4-carbonyl)amino]-1-oxoprobyl]aminomethylpyrrolidine 2-[8-hebutadecenylcarbamoyl)aminomethyl]-1 [3-[N-2.2.5.5-tetramethyl]-1.3-dimethyl-carbonyl)amino]propanoyl]pyrrolidine 3-(8-heptadecenylrubamoyl)amino-1- [3- [N- 2.2,
5.5-tetramethyl-1.3-dimethyl-4-carbonyl)amino]propanoyl]piperidine 1-(8-hebutadecenylcarbamoyl)-3[3
- [N-(2.2,5.5-tetramethyl1.3
-dimethyl-4-carbonyl)amino]probanoyl]aminobiperidine 1-(8-hebutadecenylcarbamoyl)-2[3-
[N-(2.2,5.5-tetramethyl1,3
-dimethyl-4-carponyl)amino]propanoyl]
Aminomethylpyrrolidine・4-(8-hebutadecenylcarbamoyl)amino-1-[3-[N-2.2
．． 5.5-Tetramethyl-1.3-dimethyl-4-carbonyl)amino]propanoyl]piperidine 1-(8-hebutadecenylcarbamoyl)-4[3
- [N- (2,2,5.5-tetramethyl-1,
3-dimethyl-4-carponyl)amino]propanoylcoaminopiperidine 1-(8-hebutadecenylcarbamoyl)-4piperidinyl 3-[N-(2,2.5.5tetramethyl-1.3- dimethyl-4-carbonyl)amino]
Propionate 1-(8-hebutadecenylcarbamoyl)-3piperidinyl 3- [N-(2,2,5.5-tetramethyl-1,3-dimethyl-4-carponyl)amino]
Propionate 1-(8-hebutadecenylcarbamoyl)-2piperidinyl 3- [N- (2.2,5.5-tetramethyl-1,3-dimethyl-4-carbonyl)aminocopropionate 1- (2-penzylundecanoyl)-4-pyridinyl3- [N- (2.2,5.5-tetramethyl-1
．． 3-Dioxane-4-carbonyl)amino]propionate 1-(1-penzyldecyl)carbamoyl-4-piperazinyl 3-[N-(2,2,5.5-tetramethy55-1,3-dioxane-4-carponyl) ) Amino] propionate The compound of the present invention contains at least one asymmetric carbon atom, as shown by the * symbol in the general formula (I), and is an optically active form (R-form or S-form) or an optically active form (R-form or S-form) or It includes both racemic forms.

The compound of the present invention is, for example, represented by (a) the following formula RIIO OR21 I, where R11 and R21 are the same or different and each represents a protected hydroxyl group: A compound of the following formula R3-COZ' (II) or R4-NCO (IV)56 In the formula, Zl is a hydrogen atom; a halogen atom such as CLBr; an alkoxy group such as methoxy or ethoxy; phenoxy, p-
If substituted with nitrophenoxy, 2.4 dinitrophenoxy, etc., << represents an unsubstituted phenyloxy group; R3 and R4 are as defined above, or (b) react with a compound represented by the following formula RIIO OR21 In the formula 1, Rl1, R21Sn and Z1 are as defined above. A compound represented by the following formula HX (CHJm Y Co R" (
Vl) in which R3, XSY and m are as defined above, and optionally (c) in the following formula obtained: , Y, m and n are as defined above. It can be produced by removing the hydroxyl protecting group from the compound represented by:

The reaction of the compound of formula (n) with the compound of formula (I[[) in process (a) and the reaction of the compound of formula (V) with the compound of formula (Vl) in process (b) is usually carried out in a suitable solvent. For example, aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane; esters such as methyl acetate and ethyl acetate; halogenated materials such as methylene chloride, chloroform, and carbon tetrachloride. Hydrocarbons; high-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide; alcohols such as methanol and ethanol; water and the like can be used alone or in a mixed solvent. This reaction is generally -78
C. to the boiling point of the solvent used, preferably from about -10.degree. C. to the boiling point of the solvent used. Furthermore, in method (a) and method (b), a catalyst or a reaction promoter can also be used in the reaction. Examples of the catalyst or reaction promoter used include dicyclohexylcarbodiimide, diisopropylcarbodiimide,
Carposiimides such as 1-ethyl-3-(3-dimethylaminopropyl)monocarbodiimide hydrochloride: acetic anhydride,
Examples include acid anhydrides such as benzoic anhydride; inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; and organic bases such as triethylamine, diethylamine, dimethylamine, diisopropylamine, and pyridine. The amount of these catalysts or reaction promoters is 0.01 to 10% relative to compound (If) or compound (IV).
It can be used in an equivalent amount, preferably within a range of 0.1 to 1.1 equivalents.

59-Also, compound (If) of compound (II[) or (IV)
Although there is no strict limit on the usage rate for
Compound (III) or (rV) is usually 0.8 to 1.2 mol, preferably 1.0 to 1 mol, per 1 mol of compound (■).
．． It can be used within the range of 1 mol. Similarly, compound (V) is usually 0.8 to 1 mole of compound (■).
It can be used within the range of 1.2 mol, preferably 1.0 to 1.1 mol.

In method (C), the reaction for removing the hydroxyl protecting group from compound (I-1) can be carried out by hydrolysis in a solvent in the presence of an appropriate catalyst. for example,
Aromatic hydrocarbons such as benzene, toluene, and xylene:
Ethers such as ethyl ether, tetrahydrofuran, and dioxane; Esters such as methyl acetate and ethyl acetate;
Halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride; High-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol; Water; Organic acids such as acetic acid and propionic acid; The reaction can be carried out using ketones such as acetone, methyl ethyl ketone, etc. alone or in a mixed solvent at a temperature ranging from 78° C. to the boiling point temperature of the solvent used, preferably from about 10° C. to the boiling point temperature of the solvent used. Catalysts that can be used include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; organic bases such as triethylamine, diethylamine, dimethylamine, diisopropylamine, and pyridine; hydrochloric acid, nitric acid, sulfuric acid, etc. Mineral acids; Hydrogen halides such as hydrogen fluoride, hydrogen bromide, and hydrogen iodide; Organic acids such as trifluoroacetic acid and trichloroacetic acid. Furthermore, the protecting group can be removed by catalytic hydrogenation using a suitable metal catalyst according to a conventional method. As the metal catalyst that can be used in this case, common hydrogenation catalysts such as nickel, palladium, rhodium, and platinum are used.

The products obtained by each of the above methods can be separated or purified from the reaction mixture by using a suitable combination of methods known per se, such as crystallization, chromatographic extraction, filtration, etc. can.

Formula (V) used as starting material in the above method
, (n) and (VI) can be produced as described below.

[Production of compound of formula (V)] Step 1: 110 0H 1ku Step 2: (V a) 10 Ph CHZL no on 1ku → (V-b) Step 3: Step 4: Step 5: Step 6: ( V-a) (v-d) In the above formula, M represents a hydrogen atom; an alkali metal atom such as sodium or potassium, or an alkaline earth metal atom such as magnesium or calcium; L represents OH, Cl
, BrSl or N2, R"R"sn and Zl
is as defined above.

Step 1: In this step, bantoyl lactone and ω-aminocarboxylic acid are reacted to synthesize compound (V-a). Vantoylactone is (D) (L) and (DL)
Either of them may be used. Examples of ω-aminocarboxylic acids include aminoacetic acid (glycine), 3-aminopropionic acid (β-alanine), 4-aminobutyric acid (γ-aminobutyric acid, GABA), 5-aminovaleric acid, and the like. The reaction is preferably carried out using a solvent, such as aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane; and high-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide. alcohols such as methanol and ethanol; water can be used alone or in combination. The reaction can generally be carried out at a temperature ranging from about 0° C. to the boiling point of the solvent used, preferably from room temperature to the boiling point of the solvent used. It is preferable to use a catalyst for this reaction, and such catalysts include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; organic bases such as triethylamine, diethylamine, dimethylamine, diisopyramine, and pyridine. Examples include bases. These catalysts are used in an amount of 0.01 to 10 equivalents, preferably 0.1 to 1.0 equivalents, relative to bantoyl lactone.
It can be used within the range of 1 equivalent.

Step 2: In this step, compound (Va) synthesized in Step 1 is benzylated to convert it into compound (V-b). As the benzylation reagent, benzyl halides such as benzyl chloride, benzyl bromide, and benzyl iodide; benzyl alcohol; phenyldiazomethane and the like are used. This reaction is carried out in a suitable solvent, for example, aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as ethyl ether, tetrahydrofuran and dioxane; esters such as methyl acetate and ethyl acetate; methylene chloride, Halogenated hydrocarbons such as chloroform and carbon tetrachloride; High-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol;
Ketones such as acetone and methyl ethyl ketone; Can be carried out in a single or mixed solvent such as water at a temperature usually from -78°C to the boiling point of the solvent used, preferably from -10°C to the boiling point of the solvent used. can. Moreover, a catalyst or a reaction promoter can also be used in this reaction. Such catalysts or reaction promoters include, for example, carbodiimides such as dicyclohexylcarpodiimide, diisobutylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carpodiimide hydrochloride; acetic anhydride, benzoic anhydride; acid anhydrides such as; inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate; and organic bases such as triethylamine, diethylamine, dimethylamine, diisobutyramine, and pyridine. These catalysts or reaction promoters are used in an amount of 0.01 to 10 equivalents, preferably 0.01 to 10 equivalents based on compound (V-a).
．． It can be used within the range of 1 to 1.1 equivalents.

Step 3: In this step, the compound synthesized in the previous step 2 (V-
This is a step of protecting the hydroxyl group of b) to synthesize compound (Vc). Reaction reagents for introducing protecting groups (Rll, R21) include, for example, acid anhydrides such as acetic anhydride and benzoic anhydride; acid chlorides such as acetyl chloride and benzoyl chloride;
Organic acids such as acetic acid, benzoic acid, and p-toluenesulfonic acid; Orthoesters such as ethyl orthoformate and methyl orthoformate; Ketones such as acetone and cyclohexanone; Aldehydes such as benzaldehyde and acetaldehyde; Trimethylsilyl chloride and dimethylphenylsilyl chloride Silylating agents such as diazomethane and dimethyl sulfate; Alkylating agents such as methyl iodide and benzyl chloride; and alkyl halides such as methyl iodide and benzyl chloride. This reaction is carried out in a suitable solvent, such as aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane; esters such as methyl acetate and ethyl acetate; methylene chloride, Halogenated hydrocarbons such as chloroformamide and carbon tetrachloride; High boiling point polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol; Ketones such as acetone and methyl ethyl ketone; In single or mixed solvents such as water. , -78°C to the boiling point of the solvent used, preferably from about -10°C to the boiling point of the solvent used. Moreover, a catalyst or a reaction promoter can also be used in this reaction. Such catalysts or reaction promoters include, for example, carbodiimides such as dicyclohexylcarbodiimide, diisopropylcarpodiimide, and 1-ethyl-3-(3-dimethylaminopropyl)monocarpodiimide hydrochloride;
Acid anhydrides such as acetic anhydride and benzoic anhydride; inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; triethylamine, diethylamine, dimethylamine, diisopropylamine, pyridine, etc. Organic bases: Organic acids such as acetic acid, p-toluenesulfonic acid, camphorsulfonic acid, etc. These catalysts or reaction promoters are compounds (v-
0.01 to 10 equivalents to b), preferably 0.1 to 10 equivalents
It can be used within the range of 1.1 equivalent.

Step 4: In this step, compound (V-c) is converted into compound (V-d) by hydrolysis or catalytic hydrogenation. This reaction can be carried out in a solvent using a suitable catalyst. Hydrolysis can be carried out, for example, by aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane; esters such as methyl acetate and ethyl acetate; methylene chloride, chloroform,
Halogenated hydrocarbons such as carbon tetrachloride: Polyhydric boiling point polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol; Water: Organic acids such as acetic acid and propionic acid; Ketones such as acetone and methyl ethyl ketone. -78℃ in single or mixed solvents of
to the boiling point of the solvent used, preferably at a temperature within the range of about -10°C to the boiling point of the solvent used.

Catalysts that can be used include, for example, inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; organic bases such as triethylamine, diethylamine, dimethylamine, diisopropylamine, and pyridine; hydrochloric acid, nitric acid, Examples include mineral acids such as sulfuric acid; hydrogen halides such as hydrogen fluoride, hydrogen bromide, and hydrogen iodide; and organic acids such as trifluoroacetic acid and trichloroacetic acid. On the other hand, catalytic hydrogenation can be carried out by a conventional method known per se, and nickel, palladium, rhodium, platinum, etc. are used as the metal catalyst.

Step 5: This step is a step of converting compound (V-d) into compound (V). Reagents used in this reaction include halogenating reagents such as thionyl chloride, phosphorus oxychloride, and phosphorus pentachloride; alcohols such as methanol and ethanol; and phenols such as p-nitrophenol and 2,4-dinitrophenol. Esterification reagents such as the following are used. This step is performed in a suitable solvent, for example, aromatic hydrocarbons such as benzene, toluene, xylene; ethers such as ethyl ether, tetrahydrofuran, dioxane; esters such as methyl acetate, ethyl acetate; methylene chloride, Halogenated hydrocarbons such as chloroform and carbon tetrachloride; High-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol; In single or mixed solvents such as water, -78
C. to the boiling point of the solvent used, preferably from about -10.degree. C. to the boiling point of the solvent used. It is also possible to use a catalyst or a reaction promoter for the reaction. Such catalysts or reaction promoters include dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1-ethyl-3(3-dimethylaminopropyl)
Carbodiimides such as 71 midohydrochloride; Acid anhydrides such as acetic anhydride and benzoic anhydride; Inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; Triethylamine, diethylamine, dimethylamine, Examples include organic bases such as diisopropylamine and pyridine. These catalysts or reaction promoters are compounds (V-d
), preferably 0.1 to 10 equivalents, preferably 0.1 to 1
．． It can be used within the range of 1 equivalent.

Step 6: This step is a step of synthesizing compound (V-d) from compound (V-a). Reagents that can be reacted with compound (V-a) include anhydrides such as acetic anhydride and benzoic anhydride; acid chlorides such as acetyl chloride and benzoyl chloride; organic acids such as acetic acid, benzoic acid, and p-toluenesulfonic acid. ; Orthoesters such as ethyl orthoformate and methyl orthoformate; Ketones such as acetone and cyclohexanone; Aldehydes such as benzaldehyde and acetaldehyde; Silylating agents such as trimethylsilyl chloride and dimethylphenylsilyl chloride; diazomethane, dimethyl sulfate, etc. Alkylating agents; halogenated alkyls such as methyl iodide and benzyl chloride are used. This reaction is carried out in a suitable solvent, for example, aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as ethyl ether, tetrahydrofuran and dioxane; esters such as methyl acetate and ethyl acetate; methylene chloride, Halogenated hydrocarbons such as chloroform and carbon tetrachloride; High-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol; Ketones such as acetone and methyl ethyl ketone; Single or mixed solvents such as water from -78°C to the boiling point temperature of the solvent used, preferably about -
It can be carried out at a temperature within the range of 10° C. to the boiling point temperature of the solvent used.

Moreover, a catalyst or a reaction promoter can also be used in this reaction. Such catalysts or reaction accelerators include, for example, carbodiimides such as dicyclohexylcarbodiimide, diisobutylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl) monocarbodiimide hydrochloride; acetic anhydride, benzoic anhydride; Acid anhydrides such as acids; inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate; organic bases such as triethylamine, diethylamine, dimethylamine, diisopropylamine, pyridine; acetic acid, p-toluene Sulfonic acid,
Examples include organic acids such as camphorsulfonic acid. These catalysts or reaction promoters can be used in an amount of 0.01 to 10 equivalents, preferably 0.1 to 1.1 equivalents, relative to compound (v-b).

[Production of compound of formula (n)] Compound (II) is a compound of the following formula produced as described above, in which R", R", n and Zl are as defined above. is obtained by reacting with a compound represented by the following formula HX (CHJm YH (■) where XSY and m are as defined above.

This reaction is carried out in an appropriate solvent, for example, aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane; esters such as methyl acetate and ethyl acetate; methylene chloride; Halogenated hydrocarbons such as chloroform and carbon tetrachloride; High-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol;
The reaction can be carried out in a single or mixed solvent such as water at a temperature ranging from -78°C to the boiling point of the solvent used, preferably from about -10°C to the boiling point of the solvent used. Moreover, a catalyst or a reaction promoter can also be used in the reaction. Such catalysts or reaction promoters include, for example, carbodiimides such as dicyclohexylcarposiimide, diisopropylcarpodiimide, 1-ethyl-3-(3-dimethylaminopropyl)monocarpodiimide hydrochloride, thionyl chloride, phosphorus oxychloride, etc. , halogenating reagents such as phosphorus pentachloride; acid anhydrides such as acetic anhydride and benzoic anhydride; inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; triethylamine, diethylamine, dimethylamine, Organic bases such as diisobutyramine and pyridine; organic acids such as acetic acid, p-toluenesulfonic acid and camphorsulfonic acid. These catalysts or reaction promoters are used in an amount of 0.01 to 10 equivalents, preferably 0.01 to 10 equivalents relative to compound (V).
It can be used within the range of 1 to 1.1 equivalents.

[Production of compound of formula (VI)] Compound (VI) is a compound represented by the following formula HX (CHz)m YH (■) where -76 X1Y and m are as defined above. -Co-Zl (■) In the formula, R3 and Z1 are as defined above. It is obtained by reacting with a compound represented by.

This reaction is carried out in a suitable solvent, for example, aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane; esters such as methyl acetate and ethyl acetate; methylene chloride, Halogenated hydrocarbons such as chloroform and carbon tetrachloride; High-boiling polar solvents such as dimethylformamide and dimethyl sulfoxide; Alcohols such as methanol and ethanol;
The reaction can be carried out in a single or mixed solvent such as water at a temperature ranging from -78°C to the boiling point of the solvent used, preferably from about -10°C to the boiling point of the solvent used. It is also possible to use a catalyst or a reaction promoter for the reaction. Such catalysts or reaction promoters include, for example, dicyclohexylcarbodiimide, diisopropylcarbodiimide,
Carbodiimides such as 1-ethyl-3-(3-dimethylaminoprobyl) monocarbodiimide hydrochloride; halogenating reagents such as thionyl chloride, phosphorus oxychloride, and phosphorus pentachloride; acid anhydrides such as acetic anhydride and benzoic anhydride Inorganic bases such as sodium hydroxide, potassium hydroxide ζ sodium carbonate, potassium carbonate; Organic bases such as triethylamine, diethylamine, dimethylamine, diisobrobylamine, pyridine; acetic acid, p-toluenesulfonic acid, camphor- Examples include organic acids such as sulfonic acid. These catalysts or reaction promoters are 0.01 to 0.01 to compound (V).
It can be used within the range of 10 equivalents, preferably 0.1 to 1.1 equivalents.

The compound of formula (I) provided by the present invention has excellent ACAT inhibitory activity, and can be used for the treatment, treatment, etc. of hyperlipidemia, arteriosclerosis, angina pectoris, myocardial infarction, thrombosis, etc. It is expected to be used as a preventive drug.

The ACAT inhibitory activity of the compounds of the present invention can be confirmed by the test method described below.

The ACAT inhibition test was performed using the method of Helgerud et al. [J
Internal of Lipid Research
, 22, 497 (1981)] and the method of Folch et al. [Journal o
f Biological Chemistry,
2 25, 4 97 (1957)],
This was carried out by measuring cholesteryl oleate produced from [1-''C]oleoyl CoA and intracellular cholesterol.

That is, 0.5 mj of a solution of 2 μM bovine serum albumin and 2 μM [1-+4C coreoleoyl-CoA dissolved in 0.514 M potassium phosphate buffer (pH 7.4)! Microsomal fraction (0.3 mg protein) prepared from rat liver was added to 0.514 M potassium phosphate buffer (pH 7.4).
) and 5 μl of a solution of 0-7M test drug 1 dissolved in dimethyl sulfoxide were added, and 37
Incubate at ℃ for 4 minutes.

Then methanol 4. 2 ml and chloroform8.
3 ml of water was added to stop the reaction, and 2. After adding 5 ml and shaking thoroughly, the chloroform layer was separated. After concentrating the chloroform layer, it is subjected to thin layer chromatography, the produced cholesteryl oleate is fractionated, and the radioactivity is measured using a liquid scintillation counter.

Furthermore, the ACAT inhibitory activity of each test compound is calculated based on the radioactivity of a control obtained by performing the same test as above without using a specimen.

The results are shown in Table 1 below.

In the above table, C/\Ac=CH. CO When the compound of the present invention is used as a drug for the treatment, treatment, prevention, etc. of diseases such as hyperlipidemia, arteriosclerosis, angina pectoris, myocardial infarction, thrombosis, etc., the compound may be used as a pharmaceutical auxiliary agent, e.g. scientifically acceptable carriers, diluents, excipients, binders, disintegrants,
Dosage forms suitable for administration, such as tablets, capsules, powders, etc., as well as lubricants, preservatives, stabilizers, solubilizers, flavoring agents, etc.
It can be formulated into unit dosage forms such as granules, microcapsules, syrups, elixirs, injections, and suppositories.

The content of the active ingredient in these preparations can vary widely depending on the type of compound of the present invention, the type of preparation, the purpose of use, etc., but is generally 0.5 to 90% by weight.
, preferably within the range of 5 to 60% by weight.

In solid preparations such as tablets, capsules, powders, and granules, the compounds of the invention may be added to lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, carboxymethylcellulose, starch, polyvinylpyrrolidone, metasilicic acid. Carriers or diluents such as aluminum and talc; lubricants such as magnesium stearate; disintegrants such as cellulose calcium gluconate; glutamic acid,
It can be formulated according to a conventional method together with a solubilizing agent such as aspartic acid and a stabilizer such as lactose. Furthermore, if necessary, tablets may be coated with gastric or enteric substances such as white sugar, gelatin, hydroxybrobyl cellulose, and hydroxypropyl methylcellulose, and capsules may be hard capsules or soft capsules. You can also do this.

In the case of liquid preparations such as syrups, elixirs, solutions, emulsions, suspensions, etc., the compounds of the invention are pharmaceutically acceptable. liquid medium such as purified ice, saline,
It can be formulated into a formulation by dissolving or dispersing it in a buffer, ethanol, etc., and further adding surfactants, sweeteners, flavoring agents, aromatics, preservatives, etc. as necessary.

On the other hand, injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Such injections are prepared by mixing the compound of the present invention with an aqueous diluent such as distilled water for injection or physiological saline, or a non-aqueous diluent such as polyethylene glycol, propylene glycol, olive oil, ethanol, polysorbate 80 (registered trademark), etc. It can be prepared by Furthermore, injectables may contain preservatives, wetting agents, surfactants, dispersants,
Auxiliary agents such as stabilizers and solubilizing agents may also be included.

These injections can usually be sterilized by filtration using a bacteria-retaining filter, blending with a disinfectant, or irradiation, and after these treatments, they can be made into solid preparations by methods such as freeze-drying. Sterile water or a sterile injectable diluent may be added immediately before use.

86 The compounds of the present invention can be administered orally or rectally, or parenterally, such as intravenously, intramuscularly, subcutaneously, etc. The dosage can vary depending on the type of compound used, the method of administration, the severity of the patient's symptoms to be treated, the patient's age and weight, the physician's judgment, etc., but in general, approximately 2. It is appropriate to administer ~500 mg/kg body weight once a day or in 2 to 4 divided doses. However, the above-mentioned dosage range is only a tentative guideline, and it is of course possible to administer an amount above or below the above-mentioned range depending on the judgment of the doctor, the severity of the symptoms, etc.

Hereinafter, the present invention will be explained in more detail with reference to Examples.

Reference example-1 (S)-1- (t-butoxycarbonyl)-2- (
oleoylaminomethyl)pyrrolidine 2 pieces UUff 87 EtOAc water (S)-2-aminomethyl-1-(t-butoxycarponyl)pyrrolidine 607mg and ethyl acetate 20mj!
A solution of 903 mg of oleic acid chloride dissolved in 10 ml of ethyl acetate was added dropwise to the mixture while stirring and cooling with water, and the mixture was further stirred for 2 hours. After the reaction is completed, 10mj! , and then washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 1.16 g (yield: 83%) of the title compound.

Properties: Oil mass spectrometry Molecular formula: C 28H 52N 20! Theoretical value 464. ．． 3977 Actual value 464.3969 NMR (δ, CDC Ig); 0.88 (3H,
t. J=7Hz), 1.16 - 1.37 (20H
, m) , 1.48 (9H, s) , 1.53 −
2.09 (1.0H.m), 2.17 (2H.m)
, t+ J=7Hz) , 3.13 - 3.45
(4H, m), 3.9 7 - 4.1 0 (IH
, m), 5.28 - 5.4 1 (2H, m),
7.42 (LH.brs) Reference Example-2 (R)-1-(t-butoxycarbonyl)-2-(oleiolaminomethyl)pyrrolidine EtOAc monohydrate (R)-2-aminomethyl-1-(t 401 mg of -butoxycarbonyl)pyrrolidine was dissolved in 20 ml of ethyl acetate, sodium carbonate was suspended, and a solution of 600 mg of oleic acid chloride dissolved in 10 ml of ethyl acetate was added dropwise while stirring under water cooling, followed by further stirring for 2 hours. After the reaction was completed, the reaction solution was washed with 10 ml of water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 816 mg (yield: 88%) of the title compound.

Properties: Oil mass spectrometry Molecular formula: C 28H 62N 20 3 Theoretical value 464, 3977 Actual value 464.3969 NMR (δ, CDCIs); 0.88 (3H, t,
J=7Hz), 1.16 - 1.37 (20H, m
), 1.48 (9H, s), 1.53 - 2.
09 (IOH, m), 2, 17 (2H, t,
J=790 Hz), 3.13 - 3.45 (4Hm), 3
．． 97-4.10 (IH m), 5.28-5.41 (2H, m), 7.4
2 (IH, brs), Reference Example-3 (A) 1-(t-butoxycarbonyl)-3-(oleoylamino)pipericine CO2 400 mg of 3-amino-1-(t-butoxycarbonyl)piperidine was added to 20 mjl of ethyl acetate. ! Suspend sodium carbonate and stir while cooling with water. 600mg of leicyl chloride in 10ml of ethyl acetate
A solution dissolved in was added dropwise to the mixture, and the mixture was further stirred for 2 hours. After the reaction was completed, the reaction solution was washed with 10 ml of water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 742 mg (yield: 85%) of the title compound.

Properties: Oily mass spectrometry Molecular formula: C28H5■N203 Theoretical value 46
4.3977 Actual value 464.3984 NMR (δ, CDCIs); 0.88 (3H.tJ
=7Hz), 1.17-1.41 (20H.m), 1.49-1.84 (6H,
m), 1.9 1 - 2.0 9 (4H. m)
, 2.15 (2H. t, J=7Hz), 2.
15 (2H, t, J=7Hz), 3.22 - 3
．． 53 (4H.m), 3.92-4.03 (IH, m), 5.28-5.4 1 (2H,
m), 5.47-5.62 (IH, m) (B) 3 oleoylaminopiperidine H CO2 12) aq NaHCO3 H 1-(t-butoxycarbonyl)-3-(oleoylamino)piperidine 464 mg The mixture was dissolved in 6 mf of 50% trifluoroacetic acid monochloride methylene chloride solution and stirred at room temperature for 1 hour. After the reaction, the solvent was distilled off and the residue was dissolved in ethyl acetate (20rr+7!). After neutralizing by adding a saturated aqueous sodium carbonate solution, the organic layer was dispersed. The organic layer was washed with water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 332 g (yield: 91%) of the title compound.

Properties: Oil mass spectrometry Molecular formula: C 23H 44N 20 Theoretical value 364.3453 Actual value 364.3451 NMR (δ, CD013); 0.88 (3H, t,
J=7Hz), 1.17 - 1.39 (20H,
m) , 1.54 - 1.86 (6H, m) , 1
．． 90 - 2.08 (4H, m), 2.20 (
2H. t, J=7Hz), 2.70-3.07 (4H, m), 4.00-4.07 (IH,
m), 5.28 - 5.44 (2H, m), 6
．． 4 9 - 6.6 3 (IH, m) 94 Reference example -4 1- (t-butoxycarbonyl) -3- [3
[N(2. 2. 5. 5-tetramethyl-1,3
-dioxane-4-carbonyl)amino]propanoyl]aminopiperidine 681 mg of 3-amino-1-(t-butoxycarbonyl)biperidine and 3-[N-(2,2,5.5-
tetramethyl-1,3-dioxane-4-carponyl)
0.88 g of amino]propionic acid and 5Q methylene chloride
ml of hydrochloric acid, 1-ethyl-3-
(3-Dimethylaminop 95 pills) 0.72 g of carpodiimide was added and stirred overnight. After the reaction was completed, the reaction solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain the title compound 1.
．． 38 g (yield 97%) was obtained.

Properties: Oily mass spectrometry Molecular formula: C 22H soN soe Theoretical value 441.2838 Actual value 441.2861 NMR (δ, CDC 1 s); 0.9 7 −
0.9 8 (3H, m), 1.05 (3H, s)
1.42-1.43 (3H, m), 1.46 (I
OH, s), 2.43 (2H.t, J=7Hz)
, 3.0 5 - 3.27 (2H. m), 3.28 (IH.
, d, J=12Hz), 3.36 - 3.67 (5H, m) 3.69 (
IH, d, J=12Hz), 3.87 - 4.00
(IH, m), 4.07 4,08 (IH, m), 5.93 6.02 (IH, m), 6.99-7.08 (IH, m) Reference example-5 1-oleoyl 4 Hydroxypiperidine Dissolve 2.02g of 4-hydroxypiperidine in 50ml of water, add 2.0ml of anhydrous potassium carbonate. Add 76 g of oleic acid chloride to 50 m of ethyl acetate while cooling with water and stirring.
A solution dissolved in 1 ml was added dropwise.

After stirring for 1 hour, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 5.8 g (yield: 79%) of the title compound.

Properties: Oily IR (cm”, neat); I/NH3428, νco
l628 Mass spectrometry Molecular formula: CzsH4sNO2 theoretical value 36
5.3293 Actual value 365.3309 NMR (δ, CDC13); 1.88 (3H.t
, J=7Hz) , 1.22 - 1.40 (2H,
m) 1.42 - 1.68 (4H.m), 1.8
2-2.06 (6H, m), 2.33 (2H. t, J=7
Hz), 3.10 - 3.28 (2H.m),
3.68 - 3.82 (IH, m), 3.88
- 3.98 (IH, m), 4.02 - 4.1
898 (IH, m), 5.30-5.42 (2H, m) Reference example-6 1-Oleoyl 3-hydroxypiperidine hydrochloride 1.38 g of 3-hydroxypiperidine in 40 ml of water
2.33 g of anhydrous potassium carbonate was added, and while cooling with water and stirring, 3.01 g of oleic acid chloride was dissolved in 40 ml of ethyl acetate. A solution dissolved in was added dropwise. After stirring for 1 hour, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain the title compound 3.3.
3 g (yield 91%) was obtained.

Properties: Oily IR (cm”, neat); I/OH3428, νca
l628 Mass spectrometry Molecular formula; C 28H 43N O 2 Theoretical value 365.3293 Actual value 365.3286 NMR (δ, CDC I3); 0. 88 (
3H, t, J=7Hz), 1.20 - 1.3
9 (20H.m), 1.40 - 2.09 (IO
H, m), 2.32 (2H, t.J=7Hz),
3.18-3.35 (2H, m), 3.67-
3.84 (5H.m), 5.28 - 5.40
(2H, m) Reference Example-7 (R) 1-Oleoyl-2-pyrrolidinemethanol D-405 mg of 2-pyrrolidine methanol to 1 liter of water Qr
Dissolve in RL, add 500mg of anhydrous sodium carbonate,
While cooling with water and stirring, a solution of 1.20 g of oleic acid chloride dissolved in 20 ml of ethyl acetate was added dropwise. After stirring for 1 hour, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 1.46 g (yield: 100%) of the title compound.

Properties: Oily IR (crrr', neat); νoH3430, νc
ol625 Mass spectrometry molecular formula; C 23H 4sN 0! Theoretical value 365.3293 Actual value 365.3290 NMR (δ, CDCIs); 0.83 (3H, t,
J-7Hz), 1.18 - 1.48 (20H,
m), 1.50 - 1.71 (3H. m), 1
．． 79 - 2.10 (7H, m), 2.30 (
2H,. t. J=7Hz), 3.41-3.69 (4H.m), 4.18-4.27 (LH.m
), 5.29-5.42 (2H, m), Reference Example-8 (S)-1-Oleoyl-2-pyrrolidinemethanol L-2-pyrrolidinemethanol 506mg and water 10ml
530 mg of anhydrous sodium carbonate was added thereto, and a solution of 1.50 g of oleic acid chloride dissolved in 20 m# of ethyl acetate was added dropwise while stirring while cooling with water. After stirring for 1 hour, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 1.73 g (yield: 100%) of the title compound.

Properties: Oily IR (cm”, neat); νoH34301νcol
625 Mass Spectrometry Molecular Formula i. C 23H 43N O 2NM
R Theoretical value 365.3293 Actual value 365.3288 (δ, CDCIg); 0.88 (3H, t, J=7
Hz), 1.88 - 1.48 (20H, m),
1.50 - 1.7 1 (3H, m), 1.79
- 2.10 (2H, t, J = 7Hz), 2.3 0 (2H, t, J = 7Hz), 3.4 1 - 3.6 9 (4H, m), 4.1
8-4.2 7 (IH.m), 5.29-5
．． 42 (2H, m) Reference Example-9 (S)-1 Stearoyl-2-pyrrolidine methanol EtOAc Water L-2-pyrrolidinone methane 10 1 mg to 10 ml of water
106 mg of anhydrous sodium carbonate was added, and while stirring while cooling with water, 303 mg of stearic acid chloride was dissolved in 20 mj of ethyl acetate. A solution dissolved in water was added dropwise. After stirring for 1 hour, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 366 mg (yield: 100%) of the title compound.

Properties: Oily mass spectrometry Molecular formula: C 23H 45N O 2 Theoretical value 367.3450 Actual value 367.3471 NMR (δ, CDCIs); 0.88 (3H, t+
J=7Hz), 1.17 - 1.47 (28H.m
), 1.52- 1.69 (3H, m), 1.79-
2.11 (3H.m.), 2.30 (2H.t, J=7H
z), 3.41 - 3.70 (4H, m), 4.
1 7 - 4.28 (IH, m) Reference Example-10 (S) -1 Linoleoyl-2-pyrrolidine methanol 101 mg of pyrrolidine methanol was mixed with 106 10 mj of water! Dissolved in 106 mg of anhydrous sodium carbonate
Add 315 mg of linoleic acid chloride while stirring with water cooling.
A solution prepared by dissolving this in 20 ml of ethyl acetate was added dropwise. After stirring for 1 hour, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain the title compound 360m
g (100% yield) was obtained.

Properties: Oil mass spectrometry Molecular formula: C 23H 41 N O 2 Theoretical value 363.3137 Actual value 363.3152 NMR (δ, CDCIs): 0.89 (3H, t
, J=7Hz) , 1.21 - 1.44 (14H,
m), 1.52 - 1.76 (3H.m), 1.
77-2.11 (7H, m), 2.30 (2H, t, J=7Hz)
, 2.77 (2H, t, 107 J=6Hz) , 3.42 - 3.70 (4H, m)
, 4.18 - 4.28 (IH.m) , 5.28
- 5.4 4(4H,m) Reference example-11 (A) (S)-1-penzyloxy carbonyl 2
- [1-oxo-3- [N- (2.2.5,5-
tetramethyl-1,3-dioxane-4-carponyl)
Amino]propyl]aminomethylpyrrolidine CH2Cl2 ? 234 mg of S)-2-aminomethyl-1-penzyloxylysine and 3-[N(2,2.5.5
-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionic acid (259 mg) and methylene chloride (259 mg)
Dissolve in 0 ml of 1-ethyl-3-hydrochloride while cooling with water and stirring.
(3-dimethylaminopropyl)carbodiimide 211
mg was added and stirred overnight. After the reaction was completed, the reaction solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off.

The obtained residue was purified by silica gel column chromatography to obtain 424 mg (yield: 89%) of the title compound.

Properties: Oily mass spectrometry Molecular formula: C2sHs■N 30a Theoretical value
475.2682 Actual value 475.2701 NMR (δ, CDCIs); 0.98 (3H, s)
, 1.04 (3H, s) 1.42 (3H, s
) , 1.46 (3H.s) , 1.62 −
2.13 (4H, m) , 2.30 - (B) 2.44 (2H, m) , 3.163.62 (
4H, m, ) , 3.27 (IH, d, J = 12Hz
), 3.68 (IH, d, J=12Hz), 3.92 −
4.09 (IH, m), 4.07 (IH,
s), 5.075.24 (2H, m), 7.
05 - 7.16 (LH, m), 7.17 -
7.25 (LH, m, 7.28 - 7.48 (
5H,m) (S)-2-[1-oxo3-(2,2,5.
5-Tetramethyl-1,3-dioxane-4-carbonylamino)propylcoaminomethylpyrrolidine 110 MeOH (S)-1-penzyloxycarbonyl-2[1-oxo-3- (2,2,5.5 -tetramethyl-1.3-
424 mg of dioxane-4-carponylamino)probyl]aminomethylpyrrolidine was dissolved in 20 ml of methanol, 40 mg of 10% palladium on carbon carrier was added, and the mixture was stirred overnight at room temperature under a hydrogen gas atmosphere. After the reaction, the insoluble matter was filtered, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain the title compound 298m
g (yield 98%) was obtained.

Properties: Oil mass spectrometry Molecular formula: Cl7H31N304 theoretical value 3
41.2314 Actual value 341.2327 111 NMR (δ, CDCIs); 1.00 (3H, s
), 1.01 (3H,s), 1.45 (3H
,s), 1.47 (3H,s), 1.58 - 1
．． 78 (IH, m), 1.82-2.15 (3
H. m), 2.36-2.56 (2H, m), 3.07-3.85 (9H, m), 4.12 (IH, s), 7.09 (IH, t, J
=6Hz), 7.48 (IH, t.J=6Hz) Reference Example 12 (R)-1-penzyloxycarbonyl-2[1-oxo3- (2.2.5.5-tetramethyl- 1,3-
dioxane-4-carponylamino)probylcoaminomethylpyrrolidine CH2Cb (R)-2-aminomethyl-1-penzyloxycarbonylbi-lysine 750 mg and 3-[N- (2,2,5
．． 829 mg of 5-tetramethyl-1,3-dioxane-4-carponyl)amino]propionic acid and 50 m7 of methylene chloride! 613 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added to the mixture under water-cooling and stirring, and the mixture was stirred overnight. After the reaction was completed, the reaction solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 1.10 g of the title compound (
A yield of 72% was obtained.

Properties: Oily mass spectrometry Molecular formula: C2sH37NsOa113 Theoretical value 475.2682 Actual value 475.2701 NMR (δ, CDCIg); 0.96 (3H,
s), 1.03 (3H, s), 1.4
1 (3H.s), 1.46 (3H,
s), 1.6 5 - 2.1 7 (4H, m),
2.33 (2H, t, J=6Hz), 3.
14 - 3.32 (IH, m), 3.27 (
LH, d, J=12Hz), 3.35 - 3.6
3 (5H.m), 3.68 (IH, d, J
= 12Hz), 3.93 - 4.09 (IH, m
), 4.07 (IH, s), 5.07-
5.28 (2H, m), 7.01 -7.1 6
(IH.m), 7.20 -7.44 (6H
, m) Reference example-13 Benzyl 3- [N- (2.4-dihydroxy 3,
3-dimethyl-1-oxo)amino]propionate 114 Calcium pantothenate 75 g and benzyl bromide 53.8
g was dissolved in dimethylformamide 11 and stirred at 100°C overnight. After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was dissolved in water and extracted with ethyl acetate. water the organic layer,
Next, it was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off, leaving 90.3 g of the title compound as a residue.
(yield 93%).

Properties: Oily IR (cm”, neat); νcol738, -1
15 1662 Mass spectrometry Molecular formula; C+aHzsNOs theoretical value 30
9.1576 Actual value 309.1577 NMR (δ, CDCIs); 0.88 (3H, s)
, 1.00 (3H.s) , 2.62 (2H,
t, J=7 Hz), 3.45 (IH, d, J=11 Hz), 3.48 (IH, d, J=11 Hz), 3. 52 - 3.64 (2H, m),
3.99 (IH, s), 5.14 (2H,
s), 7.10 - 7.20 (LH. m),
7.33 - 7.42 (5H, m) Reference example-14 Benzyl 3- [N- (2,2,5.5-tetramethyl-1,3-dioxane-4-carbonyl)amino]
Dissolve 90 g of propionate benzyl 3-[(2.4-dihydroxy-3.3-dimethyl-1-oxo)aminocopropionone} in 700 ml of acetone and add 5.6 g of p-toluenesulfonic acid monohydrate. and stirred at room temperature overnight. After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate, water, then saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 85 g (yield: 84%) of the title compound.

Properties: Oily 117 IR (cm”, neat): νNH3456νゎ.1740, 1676 Mass spectrometry Molecular formula: Cl9H27NO6 Theoretical value 34
9.1889 Actual value 349.1882 NMR (δ, CDC13): 0.94 (3H, s)
, 1.03 (3H, s) , 1.41 (3H,
s), 1.44 (3H, s), 2.62
(2H, t, J=7Hz), 3.28 (IH, d, J
= 12Hz), 3.67 (IH, d, J = 12Hz)
, 3.42-3.65 (2H, m), 4.07 (IH, s), 5.14 (2H.
s) 6.90 - 7.10 (IH.m), 7
．． 30 - 7.40 (5H, m) Reference example -15 3- [N- (2,2.5.5-tetramethyl-1
,3-dioxane-4-carbonyl)aminocopropionic acid 118 Benzyl 3-[N-(2.2,5.5-tetramethyl-1.3-dioxane-4-carbonyl)amino]
Dissolve 35 g of propionate in 350 ml of methanol, and add 100 ml of 1N Seizoda aqueous solution (
1 was added and stirred for 1 hour. After the reaction was completed, methanol was distilled off under reduced pressure, and the aqueous layer was extracted with ethyl acetate. 1 in the water layer
The mixture was made acidic by adding normal hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and then with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 20.4 g (yield 78%) of the title compound as a residue.

Properties: Melting point 87.2-89.2°C 119 IR (cm”, neat); l/MII3420S
νco1734, 1636 Mass spectrometry Molecular formula; C 12H 2 1 N O s
Theoretical value 259.1419 Actual value 259.1425 NMR (δ, CDCIs); 0.98 (3H.s)
, 1.04 (3H, s) , 1.43 (3H,
s), 1.46 (3H, s), 2.62
(2H, t.J=7Hz), 3.29 (IH.d,J
=12Hz), 3.68 (IH.d,J=12Hz)
, 3.43 - 3.66 (2H, m), 4.1
1 (IH.s), 6.90 - 710 (I
H, m) Reference example-16 Benzyl 3- [N- (5,5-dimethyl-2phenyl-1,3-dioxane-4-carbonyl)amino]
Propionate benzyl 3- [N- (2,4-dihydroxy 3
．． 3.09 g of 3-dimethyl-1-oxo)amino]propionate and benzaldehyde dimethyl acetal6.
09 g of p-1-luenesulfonic acid and 0.19 g of p-1-luenesulfonic acid were dissolved in 100 mf of benzene and refluxed for 2 hours while removing water produced azeotropically.

After the reaction was completed, the reaction solution was washed with saturated aqueous sodium bicarbonate, water, and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 3.18 g (yield: 80%) of the title compound 121.

Properties: Oily IR (cm-'.neat); νNI+3456%
νc. 1740.1676 Mass spectrometry Molecular formula; Cl9827NOS theoretical value 397
．． 1889 Actual value 397.1882 NMR (δ, CDCI3); 1.08 (3H, s
), 1.10 (3H, s) , 2.62 (2
H, t, J=6Hz), 3.68 (IH,
d, l-11Hz), 3.45 3.64 (2H, m), 3.72 (IH, d
, J=IHz), 4.09 (IH, s)
, 5.10 (2H.s), 5.51 (IHs)
, 6.92 7.04 (IH. m) ,? ．． 387.52 (I
OH. m) Reference example-17 Benzyl 3- [N- (3.3-dimethyl-1.5
dioxaspi mouth [5. 5] Dodecane-2-cal 12
2 Ponyl) Amino] Propionate benzyl 3- [N- (2,4-dihydroxy 3
-dimethyl-1-oxo)amino]propionate3.
09g, cyclohexanone 1.47g and p-}luenesulfonic acid 0.19g and benzene 100rr+j! The mixture was dissolved in water and refluxed for 2 hours while removing water produced azeotropically. After the reaction was completed, the reaction solution was washed with saturated aqueous sodium bicarbonate, water, and then with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to obtain 3.07 g (yield: 7123, 9%) of the title compound.

Properties: Oily IR (cm-', neat); νcal738-1
680 Mass spectrometry Molecular formula; C22H11NOS theoretical value 38
9.2202 Actual value 389.2214 NMR (δ, CDC]3); 0.95 (3H,S)
, 1.03 (3H.s) , 1.32 -1.5
0 (4H, m), 1.54 -1.70 (4H
, m), 1.78 -1.90 (2H. m)
, 2.62 (2H, t, J=7Hz), 3.
25 (IH, d, J=12Hz), 3.46- 3.66 (2H. m), 3.69 (IH. d.
J=12Hz), 4.08 (IH.s), 5.14 (2H.s), 7.00-
7.10 (IH.m), 7.30 - 7.42
(5H, m) Reference example-18 3- [N- (5.5-dimethyl-2-phenyl 1
, 3-dioxane-4-carbonyl)amino]benzylpropionate 3 [N-'(5,5-dimethyl-2-phenyl-1,3-dioxane-4-carbonyl)amino]propione}1. Og was dissolved in 20 ml of methanol, and while stirring under water cooling, 10 ml of 1N caustic soda aqueous solution was added, and the mixture was stirred for 2 hours. After the reaction was completed, methanol was distilled off under reduced pressure, and the aqueous layer was extracted with ethyl acetate. The aqueous layer was made acidic by adding 1N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water and then with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 0.77 g (quantitative yield) of the title compound as a residue.

Properties: Oily rR (cm-'.neat): L/Nll3420
, νcol732, 1636 Mass spectrometry Molecular formula: CI6H21NOS theoretical value 30
7.1419 Actual value 307.1423 NMR (δ, CDC]3); 1.11 (3H, s)
, 2.62 (2H. t. J = 7Hz), 3
．． 28 (IH, d.J=12Hz), 3.44-3.
64 (2H, m), 3.68 (IH, d, J=IHz), 3.73 (I
H. d. J=11Hz), 4.12 (LH.s)
, 5.51 (IH, s), 7.00- 7.
10 (IH.m), 7.38 - 7.45 (3H
, m), 126 7.45 - 7.52 (2H.m) Reference example-19 3- [N- (3.3-dimethyl-1.5-dioxaspi[5.5] dodecane-2-carbonyl)amino ]Benzyl propionate 3- [N= (3.3-dimethyl-1.
1.95 g of 5-dioxaspiro[5.5]dodecane-2-carbonyl)amino]propionate was dissolved in 20 mf of methanol, 20 mg of 10% palladium-127 carbon carrier was suspended, and the mixture was stirred overnight at room temperature under a hydrogen gas atmosphere. . After the reaction was completed, insoluble matter was filtered and the solvent was distilled off to obtain 1.50 g of the title compound.

Properties: Oily IR (cm”.neat); νcol728, 167
0 Mass spectrometry molecular formula; C+5H2sNO5 theoretical value 29
9.1732 Actual value 299.1718 NMR (δ, CDCIs); 0.99 (3H,S)
, 1.04 (3H.s) , 1.32 -1.51
(4H, m), 1.541.94 (7H, m)
, 2.64 (2H, t, J=6Hz), 3.26 (IH, d, J=12Hz), 3. 71 (IH; d, J=12Hz), 3.46 −
3.64 (2H, m), 4.12 (IH, s
), 7.08 - 7.14 (IH, m) Reference Example-20 3- [N (2,4-Diacetoxy3.3-dimethyl 1-oxobutyl)amino] 4.47 g of calcium pantothenate propionate was mixed with 2Qmj of pyridine
! 10.2 g of acetic anhydride was added, and the mixture was stirred overnight. After the reaction was completed, the reaction solution was poured into ice water and stirred for 2 hours.
The pH was adjusted to about 2 by adding normal hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was distilled off to obtain 4.19 g (yield 69%) of the title compound as a residue.

Properties; IR (cm-', neat); Mass spectrometry Molecular formula; Theoretical value Actual value NMR (δ, CDCI3). Reference example-21 4-nitrophenyl 3-[N setoxy-3.3-dimethyl-1 aminocopropionate (2.4-dia-oxobutyl) 130 3-[n- (2.4-diacetoxy3.3- Dimethyl-1-oxobutyl)amino]propionic acid 22
．． 6g and 10.4g of p-nitrophenol in 500mj of tetrahydrofuran! 15.5 g of dicyclohexylcarposiimide was added thereto, and the mixture was stirred overnight. After the reaction was completed, insoluble materials were removed and the solvent was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate, water, then saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 10.2 g (yield 32%) of the title compound as a residue.

Properties: Oily IR (cm-'.neat); l/NI13456
, νco1740, 1676 Mass spectrometry molecular formula; C+oH24N20o theoretical value 4
24.1481 Actual value 424.1467 NMR (δ, CDC1g); 1.04 (3H,S
), 1.08 (3H, s), 2.06 (3H,
S), 2.10 (3H, s), 131 2.8 4 - 2.9 1 (2H.m), 3.5
0 - 3.76 (2H, m), 3.86 (I
H. d. J=11Hz), 4.04 (IH, d
, J=11Hz), 4.93 (IH.s)
, 6.506.60 (IH.m). 7.29
(2H, d.7Hz) , 8.28 (2H, d.
7Hz) Reference Example-22 Benzyl 2-[N-(2.4-dihydroxy-3.
13.0 g of 3dimethylbutanoyl)amino]acetate vantoyl lactone, 8.3 g of glycine, and 85% potassium hydroxide were dissolved in methanol 1001111, and heated under reflux for 3 hours. The solvent was distilled off from the reaction solution under reduced pressure. After drying the residue, add 150mj of dimethylformamide! Add 18.8g of benzyl bromide and stir at room temperature for 20 minutes.
Stir for hours. The reaction solution was distilled off under reduced pressure, and the residue was dissolved in water and extracted with ethyl acetate. The organic layer was washed with water and then with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 2.8 g (43%) of the title compound 1. ) was obtained.

NMR (δ, CDCj!s); 0.95 (3H.s), 1
．． 06 (3H, s), 2.73 (2H, brs)
, 3.5 1 (iH, d, J=11Hz) , 3
．． 56 (IH, d, J=11Hz), 4.03-
4.21 (2H, m), 4.09 (IH, s),
5.19 (2H.s), 7.23-7.28
(IH,m), 7.33-7.42 (5H.Ill) Example-1 (S)-2-oleoylaminomethyl-1-[3-N-
(2.2.5.5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propanoyl]pyrrolidine H (S)-2-oleoylaminomethylpyrrolidine 910
mg and 650 mg of 3-[N-(2.2,5.5-tetramethyl-1.3-dioxane-4-carbonyl)amino]propionic acid in 10 m7 of methylene chloride! 530 mg of 1-134 ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added to the mixture under water-cooling and stirring, and the mixture was stirred at room temperature for 18 hours.

The reaction solution was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 1.05 g (59%) of the title compound.

Properties; Oil optical rotation [α]D; +5.2° (C-1.0.CHCIs) IR (cm”, neat); l/NH3336,
νc. 1656 Mass spectrometry Molecular formula; C35H63N305 theoretical value 6
05.4746 Actual value 605.4747 NMR (δ, CDC1a); 0.88 (3H, t
, J=7HZ), 0.96 (3H,s), 1.04
(3H.s), 1.19-1.39 (20H.s).
m), 1.42 (3H.s), 1.46 (3H.s
), 1.53 - 1.82 (3H, m), 135 1.85 - 2.09 (7H.m), 2.16
(2H, t.J=7Hz), 2.44 - 2.6
2 (2H, m), 3.13 - 3.23 (IH
．． m), 3.28 (IH, d, J=12Hz),
3.3 9 - 3.6 0 (5H.m), 3.69
(IH.d, J=12Hz), 4.08 (IH.d, J=12Hz), 4.08 (IH.
s), 4.214.28 (IH.m), 5.2
95.40 (2H, m), 7.09 (IH,
t, J=6Hz), 7.24 (IH.brs) Example-2 (S)-2-oleoylaminomethyl-1-[3-
[N-(2,4-dihydroxy-3.3-dimethyl-1-oxobutyl)amino]propanoylvirolidine H (S)-2-oleoylaminomethyl-1-[3-
Dissolve 500 mg of [N-(2,2,5.5-tetramethyl-1,3-dioxane-4-carbonylamino)propanoyl]picolisine in a mixed solvent of 20 ml of acetic acid and 10 ml of water, and stir at room temperature for 16 hours. did. Next, 20 ml of ethyl acetate and 2 Q ml of water were added, and the organic layer was separated. The organic layer was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 397 mg (85%) of the title compound.

137 Properties: Oil optical rotation [α] D: 5.8° (C = 1.0.CHCIs) IR (cm-', neat): I/NH3324
1νcol650 Mass spectrometry Molecular formula: CssHsaN305 theoretical value 5
65.4454 Actual value 565.4449 NMR C6, CDC Is); 0.88 (3H
．． t, J=7Hz), 0.92 (3H,s),
1.02 (3H, s), 1.21 -1.39
(20H, m), 1.71 -1. 84 (
IH. m) , 1.531.67 (2H, m)
, 1.852.09 (7H. m) , 2.17 (
2H, t, J=7Hz), 2.45-2.87 (4H.m), 3,13 3.75 (8H, m), '3.99 (IH,s
), 3.39 - 3.68 (5Hm), 3.6
8 (IH, d, J=138-12Hz), 4.08 (IH, s), 4.1 9
- 4.29 (LH.m), 5.29 - 5.40
(2H, m), 6.85-7.07 (IH.brs
), 7.36 - 7.44 (IH,m) Example-3 (R)-2-oleoylaminomethyl-1-[3[N-
(2,2,5.5-tetramethyl-1.3dioxane-4-carbonylamino)propanoyl]pyrrolidine■ RiU (R)-2-oleoylaminomethylpyrrolidine 910
mg and 650 mg of 3-[N-(2,2,5.5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionic acid were dissolved in methylene chloride, and while stirring under water cooling, 1-ethyl hydrochloride was added. Add 530 mg of 3=(3-dimethylaminopropyl)carpodiimide and stir at room temperature for 1
Stirred for 8 hours. The reaction solution was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 1.24 g (82 g) of the title compound.
%) was obtained.

Properties; Oil optical rotation [α] o: +41.5° (C”1.0, CHCls) IR (cm”, neat);
νun3336, νcol654 Mass spectrometry Molecular formula; C 35H 63N 30 s Theoretical value 605.4747 Actual value 605.4787 NMR (δ, CDC]3): 0.88 (3H,
t, J=7Hz), 0.97 (3H,s), 1
．． 04 (3H, s), 1.211.39 (2
0H, m), 1.43 (3H, s), 1.46
(3H, s), 1.55 - 1.82 (3H. m
), 1.87 - 2.09 (7H. m), 2.1
7 (2H, t, J=7Hz), 2.53 (2H, t
, J=6Hz), 3.12-3.21 (IH, m), 3.28 (IH.d, J=12Hz), 3.39 -
3.68 (5H. m), 3.68 (IH, d.
J=12Hz), 4.08 (IH, s), 4.20 4.28 (IH, m), 5.285.40 (
2H, m), 7.11 (1 H, t. J=6Hz), 7.24 (1 H, brs) Example-4 3-oleoylamino-1- [3- [N-
(2,2,5.5-tetramethyl-1.3-dioxane-4-carbonyl)amino]propanoyl]piperidine 142 1.09 g of 3-oleoylaminopiperidine and 3-
[N-(2,2,5.5-tetramethyl-1.3dioxane-4-carbonyl)amino]propionic acid 0.7
Dissolve 8 g in methylene chloride, add 1 ml of hydrochloric acid while stirring with water cooling.
-Ethyl-3- (3-dimethylaminopropyl)carbodiimide (0.58 g) was added, and the mixture was stirred at room temperature for 18 hours. The reaction solution was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 1.61 g (89%) of the title compound.

Properties; Oil optical rotation [α] o; +25.3° (C=1.0, CHCIs) IR (cm-1, neat); L/NI13316
X143 νco1652 Mass spectrometry molecular formula; C35H63N305 theoretical value 6
05.4767 Actual value 605.4749 NMR (δ, CDCI3); 0.88 (3H, t,
J=7Hz), 0.98 (3H,s), 1.04
(3H.s), 1.18 -1.39 (20H
, m) , 1.43 (3H, s) , 1.47 (
3H, s), 1.49 - 2.08 (IOH,
m), 2.16 (2H, t.J=7Hz), 2.56
(2H, t, J=6Hz), 3.01 - 3.15
(IH, m), 3.16-3.66 (4H, m)
, 3.28 (IH, d, J=12Hz), 3.68 (
IH, d, J=12Hz), 3.69 - 4.08
(2H, m), 4.07 (IH.s), 5.29
-5.40 (2H. m), 7.0 1 -7.
11 (IH, d, J=6Hz) Example-5 3-oleoylamino-1- [3- [N-
(2,4-dihydroxy-3.3-dimethyl-1-oxobutyl)amino]probanoyl]piperidine 3-oleoylamino-1- [3- [N- (2,2
, 5,5-tetramethyl-1,3-dioxane 4-carbonyl)amino]propanoylpiperidine (1.61 g) was dissolved in a mixed solvent of 20 mf of acetic acid (!) and 10 mf of water and stirred at room temperature for 16 hours. Ethyl 2 0mj
! Then, 20 liters of water were added and the organic layer was separated. The organic layer was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 1.1 g (73%) of the title compound.

Properties; Oil optical rotation [α] o: +10.4° (C=1.0, CHC Is) IR (cm”, neat); ν+i■3316, νc
ol650 Mass spectrometry Molecular formula; C 35H soN so 6 Theoretical value 565.4454 Actual value 565.4446 NMR (δ, CDCIs); 0.88 (3H, t.
J=7Hz), 0.93-0.95(3H,s)
, 1.03 (3H,s), 1.21 - 1.38
(20H, m), 1.48 - 2.09 (IO
H, m), 2.15 (2H, t, J=7Hz), 2
．． 57 (2H, t, J=6Hz), 3.05 - 3
．． 98 (7H. m), 3.47 (IH, d, J=
12Hz), 3.51 (IH, d, J=12Hz),
146 3.95 (IH.m), 5.29 -5.40
(2H, m), 5.615.86 (IH, br
s), 7.23 (IH, brs) Example-6 1-oleoyl-3-[3-(2,4-dihydroxy-3.3-dimethyl-1-oxobutylamino)propanoyl]aminobiperidine A and B3 - [3-
(2,4-dihydroxy-3,3-dimethyl-1-oxobutylamino)propanol]aminopiperidine 942 mg and sodium carbonate 1.
06 g was dissolved in 20 ml of water and 20 ml of ethyl acetate, 945 mg of oleic acid chloride was added under water cooling, and the mixture was stirred for 30 minutes. Next, the aqueous layer was removed, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain two types of the title compound. diastereomers A and B of 390 mg (22%) and 409 mg (
23%).

A Properties: Oil optical rotation [α] D; +22.5° (C = 1.0.CHC Ig) IR (cm”.neat); νNn3324, νco
l652 Mass spectrometry molecular formula; CszHseNsOs theoretical value 5
65.4453 Actual value 565.4433 NMR (δ, CDC Ig); 0.88 (3H
, t, J=7Hz), 0.91 (3H,s),
1.04 (3H,s), 1.22 -1.38
(20H, m), 1.522.09 (IOH, m)
, 2.25 -2.53 (4H.m) , 2.65 3.70 (9H.m) , 3.98 (IH, brs
), 4.04-4.31 (2H, m), 5.28
-5.4 0 (2H.m), 5.94 (LH.m)
brs), 7.50 (IH, brs) Properties; Oil optical rotation [α] o; +7.6° (C=1.0.CHC Is) IR (cm”, neat); L/sH3320sν
co1652 mass spectrometry molecular formula; C 32H 511N 30 5
Theoretical value 565.4453 Actual value 565.4461 NMR (δ, CDCI3); 0.88 (3H, t,
J=7Hz), 0.97 (3H, s), 1.
03 (3H.s), 1.22-1.38 (2
0H. m), 1.52-2.09 (IOH.m)
, 2.252.80 (6H, m) , 3.10
-4.05 (IH,s), 5.29 -5.40
(2H, m), 6.23 (IH, brs),
7.50 (IH, brs) Example-7 1-oleoyl-3-[3-(2,2,5.5-tetramethyl-1,3-dioxane-4-carbonylamino)propanoyl]amino piperidine-A -150 1-oleoyl-3-[3 (2.4
-dihydroxy-3,3-dimethyl-1-oxobutylamino)propanoyl]aminopiperidine A 1 8
0mg of acetone Qmj! 10 mg of p-}luenesulfonic acid dissolved in the solution was added, and the mixture was stirred at room temperature for 10 hours. Add 10 ml of saturated aqueous sodium hydrogen carbonate solution to the reaction solution,
After extraction with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain 176 mg (91%) of the title compound.

Properties: Oil optical rotation [α]o; +30.6° (C=1.0, CHCI!) 151 IR (cm-', neat); ! /NH3312,
νcol6 5 2, 1636 Mass spectrometry Molecular formula; C 3SH 63N 30 s Theoretical value 605.4767 Actual value 605.4789 NMR (δ, CDCIs); 0.88 (3H.t,
J=7Hz), 0.96 (3H,s), 1.04
(3H, s) , 1.21 -1.38 (20H
．． m), 1.43 (3H.s), 1.47 (3
H, s), 1.49 - 1.77 (5H, m),
1.8 1 - 2.08 (5H, m), 2.34
(2H, t, J=7Hz), 2.36 - 2.49
(2H. m), 2.98 - 3.16 (IH,
m), 3.28 (IH.d, J=12Hz), 3.
32 - 3.72 (4H, m), 3.70 (I
H, d. J=12Hz), 3.78 - 4.04 (
2H. m), 4.08 (IH.s), 5.2
9 -5.40 (2H, m), 5.996.16
(IH, m), 7.02 (IH.brs)
, Example-8 1-oleoyl-3-[3-(2,2,5.5
-Tetramethyl-1,3-dioxane-4-carbonylamino)propanoyl]amino piperidine-B 1-oleoyl-3-[3(2.4
-dihydroxy-3,3-dimethyl-1-oxobutylamino)propanoyl]aminopiperidine-B 238
mg was dissolved in 10 ml of acetone, 10 mg of p-toluenesulfonic acid was added, and the mixture was stirred at room temperature for 10 hours. Saturated aqueous sodium hydrogen carbonate solution lQmf was added to the reaction mixture, extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography. , title compound 206
mg was obtained.

Properties; Oil optical rotation [α] D; +16.0° (C=1.0, CHC13) IR (cm”, neat); I/NI+3312, ν
col654 mass spectrometry molecular formula: C36H63Nl105 theoretical value
605.4767 Actual value 605.4776 NMR (δ, CDCIs); 0.88 (3H, t,
154 J=7Hz), 0.98 (3H.s), 1.05
(3H.s), 1,181.38 (20H,
m) , 1.42 (3H,s) , 1.4 7 (3
H,s), 1.49-2.08 (IOH,m), 2
．． 34 (2'H, t, J=7Hz), 2.37
- 2.50 (2H.m), 2.90-3.07
(IH.m), 3.29 (IH,d,J=12
Hz), 3.32 - 3.73 (4H, m), 3
．． 69 (IH, d. J=12Hz), 3.76
- 4.1 1 (2H, m), 4.07 (I
H, s), 5.295.41 (2H, m)
, 5.976.11 (IH, m) , 7.02
(IH, brs), Example-9 1-oleyl-4-piperidinyl 3-[N-(2,2
, 5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate 155 1-oleoyl-4-hydroxypiveridine 1.83 g
,3- [N- (2.2,5.5-tetramethyl-
1.3-dioxane-4-carponyl)amino]propionic acid 1.3 g, dicyclohexylupodiimide 1.0
3 g and 4-(N,N-dimethylamino)pyridine 0.
61 g was dissolved in 60 ml of toluene and heated under reflux overnight. After the reaction was completed, it was cooled, the precipitate was removed, and the organic layer was mixed with water and I
Wash with N-hydrochloric acid, then saturated saline, and dry with anhydrous sodium sulfate. Ta. The solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain 1.95 g of the title compound (
65%).

Properties: Oily IR (cm-l, neat): νcol740, 16
60 Mass spectrometry molecular formula; CssHa■N206 theoretical value 6
06.4606 Actual value 606.4587 NMR (δ, CDCIg); 0.88 (3H, t,
J=7Hz), 0.96 (3H,s), 1.04
(3H, s) , 1.16 -1.40 (19H
, m) , 1.43 (3H,s) , 1.46 (3
H,s), 1.50 - 1.77 (6H.m),
1.76 - 2.04 (6H, m), 2.32 (
2H,t,J=6Hz), 2.58 (2H.t,J=
6Hz), 3.29 (IH.d, J=12Hz), 3
．． 26-3.70 (4H.m), 3.69
(IH, d.J=12Hz), 3.88 - 4.00
(IH, m), 4.08 (IH, s), 4
．． 965.06 (IH.m), 5.30 -5.
42 (2H, m), 6.886.96 (IH
, m) Example-10 1-oleoyl-4-piperidinyl 3-[N-(2.
4-dihydro-3,3-dimethyl-1-oxobutyl)
Amino] propionate U U 158 1-oleoyl-4-piperidine 3-[N-(2,2
, 1.51 g of 5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate was dissolved in acetic acid 2
0ml and 10ml of water! and stirred at room temperature for 16 hours. Next, 20 ml of ethyl acetate and 20 ml of water were added, and the organic layer was separated. The organic layer was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 1.37 g (97%) of the title compound.

Properties: Oily IR (cm”, neat); νNl+3436, ν
co1740, 1658 Mass spectrometry Molecular formula; C 32H 511N 20 a
Theoretical value 566.4294 Actual value 566.4318 NMR (δ, CDCIs); 0.88 (3H, t,
J=7Hz), 0.92 (3H,s), 1.02
(3H.s), 1.201.40 (21H,
m) , 1.56 -159 1.72 (4H, m) , 1.80 -2.10
(5H.m), 2.32 (2H.t,
J = 7Hz), 2.59 (2H, t, J = 6Hz), 3
．． 2 0-4.10 (IOH, m), 4.96-5
．． 06 (IH.m), 4.965.06 (I
H. m), 5.30 -5.42 (2H, m)
, 7, 14-7.24 (IH, m) Example-11 1-oleoyl-4-piperidinyl 3-[N(2.4
-Diacetoxy-3.3-dimethyl-1-oxobutyl)amino]propionate 1-oleoyl-4-piperidinyl 3-[N(2.4-dihydroxy-3.3-dimethyl-1-oxobutyl)amino]propionate 53
0 mg was dissolved in 5 ml of pyridine, 10 ml of acetic anhydride was added, and the mixture was stirred at room temperature overnight. Pour the reaction solution into ice water,
After extraction with ethyl acetate, the organic layer was washed with a saturated aqueous sodium bicarbonate solution, water, and then with saturated brine, and dried over anhydrous sodium sulfate.

After distilling off the solvent, the residue was subjected to silica gel column chromatography to obtain 610 mg of the title compound.

Properties: Oily IR (cm”, neat); LICO1746, 1
642? Quantitative analysis Molecular formula csa}Is■N208 theoretical value 6
50.4505 Actual value 650.4502 NMR (δ, CDCIs); 0.88 (3H,
t, J =7Hz), 1.02 (3H, s
), 1.07 (3H,s), 1.20 -1.4
0 (208, m), 1.56 -1.70 (
58,m), 1.80 -2.08 (6H.m)
, 2.07 (3H, s) , 2.15 (
2H. t, J=6Hz), 3.26 - 3
．． 70 (6H.m), 3.83 (LH, d.
J=1 1Hz), 3.82-3.94(I
H, m), 4.04 (IH, d, J=11Hz)
, 4.96 (IH.S), 4.93 - 5.
02 (IH, m), 5.30 (2H, m), 6.
52 -6.60 (IH, m) Example-12 1-oleoyl-3-piperidinyl 3-[N-(2.
4-dihydroxy-3.3-dimethyl--162-1-oxobutyl) amino] propionate 1-oleoyl 3 3.30 g of hydroxypiperidine and 3-IN-(2,2,5.5-tetrame163 tyl-1) .3-dioxane-4-carbonyl)amino]
2.33 g of propionic acid, 1.03 g of dicyclohexyllupodiimide, and 0.61 g of 4-(N,N-dimethylamino)pyridine were combined with 60 mj of toluene! The mixture was dissolved in water and heated under reflux overnight. After the reaction was completed, the mixture was cooled, the precipitate was removed, and the organic layer was washed with water, IN hydrochloric acid, and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off and the crude 1-
Oleoyl-3-piperidino 3- [N- (2
．． 2.5.5-tetramethyl-1,3-dioxane-4
-carbonyl)amino]probionate was obtained. This stuff is 20mj of acetic acid! and 10 ml of water, and stirred at room temperature for 16 hours. Then 20 ethyl acetate
ml and 20 ml of water were added, and the organic layer was separated. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off.
The residue was purified by silica gel column chromatography to obtain 1.25 g (45%) and 1.36 g (49%) of two diastereomers ASB of the title compound, respectively.
) was obtained.

A Properties - Oil optical rotation [α]D; +19.5° (C=1.0, CHC Is) IR (cm”, neat); l/NH3312%νc
o1740, 1652 Molecular formula; C 32H sgN 20 g Theoretical value 56
6.4294 Actual value 566.4297 NMR (δ, CDCIg); 0.88 (3H, t.
J=7Hz), 0.90 (3H,s), 1.07
(3H,s), 1.22-1.39 (20H,m)
, 1.452.09 (IOH, m) , 2.31
(2H, t, J=7}1z), 2.33-3.18
(6H, m), 3.29- 3.58 (3H, m)
, 3.70 -3.89 (3H, m) , 4.0
2 (IH, brs), 4.81-4.93 (2H. m), 5.2 9 - 5.4 1 Mass spectrometry (2H, m), 7.38 (IH. brS), ? Properties Oil optical rotation [α] D; +32.8° (C = 1.0. CHC Ig) IR (cnr', neat); l/N} +3312,
νC. 1740, 1650 Mass spectrometry Molecular formula: C3■Hs a N 2 0 s Theoretical value 566.4294 Actual value 566.4394 NMR (δ, CDC Ig): 0.88 (3H
．． t, J=7Hz), 1.00 (3H,s),
1.06 (3H, s), 1.22 -1.38
(20H, m), 1.522.08 (IOH.
m), 2.15 -2.63 (4H. m),
2.92 - 3.84 (7H, m), 4.00
(IH, s) , 4.4 7 - 4.58 (IH,
m), 4.96 (IH.brs), 5.29=1
66 -5.40 (2H, m), 7.42 (IH, brs) Example-13 1-oleoyl 3-piperidinyl 3-[N (2,2 5.5-tetramethyl-1.3-dioxane) 4-Carponyl)amino] Propionate A 1-oleoyl-3 Piperidinyl 3 [N- 167 ? 2,4-dihydroxy-3,3-dimethyl-1oxobutyl)amino]probionate A in acetone 10m
10 mg of p-}luenesulfonic acid was added to the solution, and the mixture was stirred at room temperature for 10 hours. Add 10 mj of saturated aqueous sodium hydrogen carbonate solution to the reaction solution! was added, extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 479 mg of the title compound (7
9%).

Properties: Oily optical rotation [α. ;+18.8゜(C=1.0,CHCI,) IR (cm-1.neat);I/NH33121ν
col 7 4 0, 1678, 1650 Mass spectrometry Molecular formula; cssHa■N206 Theoretical value 606.4607 Actual value 606.4635 NMR (δ, CDCl3); 0.88 (3H, t,
J=7Hz). 0.90 (3H, s), 1.04 (
3H,s), 1.21 -1.38 (20H,m)
, 1.42 (3H, s) , 1.46 (3H, s)
, 1.40 - 2.09 (IOH, m), 2.3
0 (2H, t, J=7Hz), 2.4 5 - 2.
6 3 (2H, m), 3.27 (LH, d, J=
12Hz), 3.32 - 3.70 (6H, m)
, 3.66 (IH, d, J=12Hz), 4.07
(IH, s) , 4.81 (IH, b r s)
, 5.29 - 5.40 (2H, m) , 6.79
- 7.02 (IH, brs) Example-14 1-oleoyl-3-piperidinyl 3-[N- (2
．． 2, 5. 5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate B 1-oleoyl-3-piperidinyl 3-[N(2.4
-dihydroxy-3,3-dimethyl-1-oxobutyl)
Amino]propionate B 567 mg to acetone 10
10 mg of p-}luenesulfonic acid dissolved in mA' was added, and the mixture was stirred at room temperature for 10 hours. Add 10 ml of saturated aqueous sodium hydrogen carbonate solution to the reaction mixture, extract with ethyl acetate, wash the organic phase with saturated brine, and dry over anhydrous sodium sulfate.
70 After drying, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 490 mg of the title compound (
81%).

Properties: Oil optical rotation [α]n; +22.8° (C=1.0, CHCI3) I R (cm”, ne at): νN
u33 1 2, νco174011680, 1652 Mass spectrometry molecular formula; C ssH ll2N 20 e
Theoretical value 606.4607 Actual value 606.4607 NMR (δ, CDCa); 0.88 (3H.t,
J=7Hz). 0.98 (3H.s), 1.05 (
3H, s), 1.211.38 (20H, m
) , 1.42 (3H,s) , 1.45 (3H,s
), 1.50 - 2.05 (IOH, m), 2.
30 (2H, t.J=7Hz), 2.54 (2H.
t. J=6Hz), 3.24 (LH, d, J=12H
z), 171 3.32 - 3.72 (6H, m), 3.66 (
IH. d. J=12Hz), 4.06 (IH,s)
, 4.75 4.85 (IH, m) , 5.29 -5.40 (
2H. m) , 7.81 -7.93 (LH, m) Example-15 1-oleoyl-2-(2S) 1-pyrrolidinylmethyl 3- [N- (2,2,5.5-tetramethyl −
1.3-dioxane-4-carbonyl)amino]propionate 0 (S)-1-oleoyl-2-pyrrolidinemethanol 1
．． 83 g and 3-EN-(2,2,5.5-tetramethyl-1.3-dioxane-4-carbonyl)aminocopropionic acid 1.30 g and dicyclohexylcarbodiimide 1.03 g and H4-(N, N-dimethylamino)pyridine 0.61gt-}luene 60ml! The solution was dissolved in water and heated under reflux overnight. After the reaction was completed, the mixture was cooled, the precipitate was removed, and the organic layer was washed with water, IN hydrochloric acid, and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was subjected to E/silica gel column stomatography.
2.24 g (74%) of the title compound was obtained.

Properties: Oily optical rotation [α'Jor 10. 5°173? C=1.0, CHCIs) IR (cm-'.neat); I/NH3312, ν
co1740, 1680, 1652 Mass spectrometry Molecular formula; CssHa N206 theoretical value 60
6.4607 Actual value 606.4589 NMR (δ, CDCl3); 0.88 (3H, t,
J=7Hz), 0.90 (3H,s), 1.04
(3H.s), 1.20 1.40 (20H.m), 1.43 (3H.s)
, 1.46 (3H,s), 1.56 - 1.72
(2H, m), 1.75 - 2.09 (8H, m
), 2.25 (2H, t, J=7Hz), 2.57
(2H, t, J=6Hz), 3.28 (IH, d, J
=12Hz), 3.35 - 3.64 (4H, m)
, 3.68 (LH.d.J=12Hz), 4.05
- 4.28 (3H, m), 4.3 1 - 4.4
1 (IH, m), 174 5.29 - 5.41 (2H.m), 6.90
- 7.04 (IH, m) Example-16 1-oleoyl-2-(2R) 1-pyrrolidinylmethyl 3- [N- (2,2,5.5-tetramethyl-1.3-dioxane) -4-Carbonyl)amino]propionate (R) 1 oleoyl-2 pyrrolidinemeth 175 1.46 g of nol and 3-[N- (2.2,5.5-
tetramethyl-1,3-dioxane-4-carbonyl)
1.04 g of amino]propionic acid, 1.03 g of dicyclohexylcarbodiimide, and 0.61 g of 4-(NN-dimethylamino)pyridine were dissolved in 60 ml of toluene.
Heated at reflux overnight. After the reaction was completed, the mixture was cooled, the precipitate was removed, and the organic layer was washed with water, IN hydrochloric acid, and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain 1.62 g (67%) of the title compound.

Properties: Oil optical rotation [α]o; +44.9° (C=1.0. CHC13) IR (cm”, neat); LINI+33121ν
co1742, 1682, 1652 Mass spectrometry Molecular formula; C ssH 62N 20 6 Theoretical value 606.4607 Actual value 606.4605 NMR (δ, CDC Ig); 0.88 (3H
．． t, J=7Hz), 1.97 (3H, s),
1.04 (3H, s), 1.191.39
(20H, m), 1.43 (3H, s), 1.4
6 (3H,s), 1.55 - 2.09 (I
OH, m), 2.26 (2H, t, J=7Hz
), 2.57 (2H, t.J=6Hz), 3.
22 (LH, d, J=12Hz), 3.36 −
3.70 (4H, m), 3.68 (IH, d,
J=12Hz), 4.08 (IH.s), 4
．． 09 -4.24 (2H, m), 4.30 -
4.43 (LH.m), 5.295.40 (
2H. m) , 6.92 -7.05 (LH, m) Example-17 1-stearoyl-2-(2S) 1-pyrrolidinylmethyl 3- [N- (2,2,5.5-tetramethyl-1 3-Dioxane-4-carponyl)amino]propionate (S)-1-stearoyl-2-pyrrolidinemethanol 367 mg and 3-[N-(2,2.5.5tetramethyl-1.3-dioxane-4-carbonyl) amino]
259 mg of propionic acid, 1.03 g of dicyclohexyllupodiimide, and 0.61 g of 4-(N.N-dimethylamino)pyridine were dissolved in 60 ml of toluene and heated under reflux overnight.

After the reaction was completed, it was cooled, the precipitate was removed, and the organic layer was diluted with water.
8 Washed with 1N hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain 470 mg of the title compound.
(77%).

Properties; Oil optical rotation [α]o; 5.10° (C=1.0, CHC]3) IR (cm-', neat); l/CO1742%1
650 Mass spectrometry Molecular formula; C ssH 64N 20a Theoretical value 608.4764 Actual value 608.4760 NMR (δ, CDCIs); 0.88 (3H, t,
J=7Hz), 0.97 (3H.s), 1.04
(3H, s) , 1.18 1.37 (24H, m) , 1.43 (3H, s)
, 1.46 (3H.s), 1.53 - 2.10
(IOH, m), 2.25 (3H, t, J=7H
z), 2.56 (2H.t, J=6Hz), 179 3.28 (IH.d, J=12Hz), 3.3
5 - 3.62 (4H, m), 3.68 (I
H. d. J=12Hz), 4.08 (IH.
s), 4.12 (IH, dd, J=11Hz.
4Hz), 4.23 (IH, dd, J=11Hz.4
Hz), 4.32 - 4.40 (LH, m), 6.
08 (LH, t, J=5Hz), Example-18 1-linoleoyl-2- (2S) monopyrrolidinylmethyl 3-[N- (2.2.5.5-tetramethyl-1.3- Dioxane-4-carbonyl)amino]propionate-〉O(S)-1-linoleoyl-2-pyrrolidinemethanol 363 mg and 3-[N-(2.2,5.5-tetramethyl-1.3-dioxane-4) -carponyl)amino]propionic acid 259 mg and dicyclohexyllupodiimide 1.03 g and 4-(N,N-dimethylamino)
0.61 g of pyridine was dissolved in 60 mi' of toluene and heated under reflux overnight.

After the reaction was completed, it was cooled, the precipitate was removed, and the organic layer was dissolved in water and IN.
The mixture was washed with hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain 433 mg of the title compound (
70%).

Properties; Oil optical rotation [α]D; +2.30° (C=1.0, CHCI3) IR (cm-', neat); l/NI+3312
,ν,. 1680, 1652 Mass spectrometry Molecular formula; C ssH aoN to 6 Theoretical value 604.4451 Actual value 604.4452 NMR (δ, CDC1g); 0.89 (3H, t,
J=7Hz). 0.97 (3H,s), 1.04 (
3H, s), 1.22 -1.41 (14H.
m) , 1.43 (3H, s) , 1.46 (3H
, s), 1.56 - 2.09 (IOH, m),
2.25 (2H, t.J=7Hz), 2.56 (2
H, t, J=6Hz), 2.77 (2H.t.J=6
Hz), 3.28 (IH.d, J=12Hz), 3.
3 7 - 3.6 3 (4H, m), 4.08
(IH. s) , 4.1 1 (IH, dd, J=
11Hz, 4Hz), 4.23 (LH, dd, J=11H -182 - z, 4Hz), 4.3 1 - 4.40 (IH, m
), 5.28 - 5.43 (4H, m), 6.9
8 (IH, t.J=6Hz) Example 19 1-oleoyl-2- (2S) ~pyrrolidinylmethyl 3- [N- (2.4-dihydroxy-3,
3dimethyl-1-oxobutyl)amino]propionate 1-oleoyl-2-(2S)-pyrrolidinylmethyl
3- [N- (2,2,5.5-tetramethyl-1
．． 1.5 g of 3-dioxane-4-carponyl)ami183-propionate was mixed with 20 ml of acetic acid and 10 ml of water.
It was dissolved in a mixed solvent with A' and stirred at room temperature for 16 hours.

Then ethyl acetate 20II17! Then, 20 mA' of water was added and the organic layer was separated. The organic layer was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain the title compound 1.
27g (91%) was obtained.

Properties: Oily optical rotation [α]. ;+13.4''' (C=1.0, CI
IC73) IR (cm-', neat); v N
H 3312, l/col742, l650 mass spectrometry molecular formula; CsJsaNzOs theoretical value 566. 4
294 Actual value 566. 4301 NMR (δ, CDCA's): 0. 88 (38.
t, J=7Hz), 0. 94 (31, s), 1
．． 04 (3H, s), 1. 21-1. 40 (2
0H, m), 1. 54-1. 68 (2H.m)
, 1. 69-1. 86 (111, I1), 1. 8
8-2. 09 (71, m), 2. 10-2. 3
8C3H, I1), 2. 40-2. 63 (28,
m), 3. 33-3. 71 (6H, m>, 4.
00 (IL m), 4. 03-4. 15 (2L
m), 4. 38-4. 50 (In, m), 5.
28-5. 40 (2L m), 7. 30-7. 5
2(ITI, m) Example 20 1-oleoyl-2-(2S) 1-pyrrolidinylmethyl 3- [N- (2.4-diacetoxy-3,3-
Dimethyl-1-oxobutyl)amine] propionate 1-oleoyl-2-(28)-pyrrolidinylmethyl
3-[N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]propionate 5
Dissolve 56IIlg in 5nl of pyridine and add 10ml of acetic anhydride.
ml and stirred at room temperature overnight. The reaction solution was poured into ice water and extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium bicarbonate solution, water, and then saturated brine, and dried over anhydrous sodium sulfate. After distilling off the solvent, the residue was subjected to silica gel column chromatography to obtain 463 mg (71%) of the title compound.

Properties: Oil optical rotation [α] D; -0.40° (C = 1.0, CHC
l3) IR (cm-', neat); v Nil
, V co 2748, 1646 mass spectrometry molecular formula; C36H62N20g theoretical value 650. 4506 Actual value 650. 4500 NMR (δ, CDCh); 0. 88 (3H, t,
J=7Hz), 1. 02 (311, s), 1.
07 (3L s), 1. 22-1. 38 (20H,
m), 1. 55-1. 67 (2H, fil),
1. 70-1. 85 (IH, m), 1. 88-2
．． 08 (7H, m), 2. 07 (3H, m),
2. 14 (3H, s), 2. 26(2H, t,
J=7Hz), 2. 43-2. 59 (2B, m
), 3. 35-3. 68 (4H, m), 3. 84
(IL d, J=12Hz), 4. 04(11,d
, J=12Hz), 4. 15(2+1, d, J
=6Hz), 186 4. 37-4. 45 (LIT, m), 4. 97
(IH.s), 5. 28-5. 40 (2H, m
), 6. 89-6. 96(III, II1) Example 21 (S)-1-oleoyl-2- [3- (2,2.
55-tetramethyl-1.3-noxane-4-carbonyl)amino-1-oxopipyl]aminomethylpyrrolisine (S)-2- [3- (2,2.5.5-tetramethyl1.3- dioxane-4-carbonyl)amino-1
-Oxopipill] Aminomethylpyrrolidine 321mg
was dissolved in 20 mA of methylene chloride, pyridine 187 1II1N was added, and while cooling with water, oleic acid chloride 27
A solution of 1 mg dissolved in 5 liters of methylene chloride was added dropwise,
The mixture was stirred as it was for 3 hours. After the reaction was completed, it was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain the title compound 16.
6 mg (30%) was obtained.

Properties: Oil optical rotation [α + +3.90° (C = 1.0,
CHCl3)IR(cr', neat); v Nl
l 3324, νco1676 mass spectrometry molecular formula; C
35H63N305 Theoretical value 605. 4767 Actual value 605. 4778 NMR (δ, CDCA!s); 0. 88 (3B,
t, J=7Hz), 0. 99 (38, s), 1
．． 04 (3H, s), 1. 18-1. 39(2)
0B, m), 1. 42 (3H, s), 1. 47
(3H, s), 157-1. 80 (31, m),
1. 88-2. 09 (7H, m), 2. 27(
2H, t, J=7Hz), 2. 23-2. 45
(2B, m), 3. 13-3. 23 (IL m),
3. 28 (Ill, d, J=1111z), 3.
40-3. 64 (51, m), 3.68 (IH,
d, J=11Hz), 4. 07 (1B, s), 4
．． 23-4. 31 (IH, m), 5. 29-5
．． 40 (2Hm), 7. 12 (18, t, J=
611z), 7.507. 62 (LH, m) Example 22 (R)-1-oleoyl-2 [3 (2 2.5 5-tetramethyl 1,3-dioxane 4 carbonyl)amino-1-oxopropyl]aminomethylpyrrolidine (R )-2-E3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino-1-oxoprobyl]aminomethylpyrrolidine 8
Dissolve 21'mg of oleic acid chloride in 40ml of methylene chloride, add 2ml of triethylamine, and add 697n+g of oleic acid chloride to 10ml of methylene chloride under ice cooling. A solution dissolved in was added dropwise to the mixture, and the mixture was stirred as it was for 3 hours. After the reaction was completed, it was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain 1.20 g (87%) of the title compound.

Properties: Oil optical rotation [α] D; +40.7° (C=1.0, CH
Cl3) IR (cm-', neat); v NH
3328, νcol656 mass spectrometry molecular formula: C35
H63N305 theoretical value 605. 4767 Actual value 605. 4757 NMR (δ, CDCA'3); 0. 88(3[1,
t, J=7Hz), 0. 97 (3B, s), 1
．． 04 (3H, s), 1. 21-1. 39(2)
0H, m), 1. 42 (3H, s), 1. 47
(3}1, s), 1.561. 80 (3H, m)
, 1. 88-2. 09 (7B, m), 2. 27
(2H, t, J=7Hz), 2. 40 (2H,
t, J=61]z), 3. 12-3. 20 (IH
, I1), 3. 27 (LH, d, J=12Hz)
, 3. 41-3. 64 (5B, m), 190 3. 68 (LH, d, J=12Hz), 4. 0
7 (111, s), 4. 24-4. 33 (IH,
m), 5. 29-5. 40 (2H, m), 7.
12 (IH, t, J=6}1z), 7. 60 (I
H, brs) Example 23 1-(1-pencyldecyl)carbamoyl-4-piperazinyl 3-[N-(2.2,5.5-tetramethyl-1.3-dioxane-4-carponyl)amino]propionate 1 -Oleoyl-4-hydroxypiperidine was replaced with 1-(1-penzyldecyl)carbamoyl-4-hydroxypiperidine, and the reaction was carried out in the same manner as in Example 9 to obtain the title compound.

Properties: Wax-like Molecular formula: C ssH tyN so s Molecular weight +615.86 Mass spectrometry calculated value: 615. 4247 Actual value: 6
15.4222 (C=1, 0, CHCj!3) IR (νneatcm-'): 2932, 2860
, 1734 NMR (δ, CDCj!s): 0.88 (3
H, t, J=7TIz), 0.96 (3H, S), 1
．． 04 (3H, s), 1. 16-1. 38(1)
6H, m), 1.42 (3Ls), 1. 46 (3H
, s), 1. 48-1. 89 (4H, m), 2
．． 57 (2Tl, t, J=6Hz), 2. 72
-2. 87 (2H, m), 3. 05-3. 21
(2tl, n+), 3. 28 (18, d, J=
12Hz), 3. 41-3. 66 (4H, m)
, 3.69 (IL d. J= 1211z), 4.
Ol-4. 07 (ITI, +1), 4. 08(1)
1. s), 4. 15-4. 23 (14 m), 4
．． 914. 99 (IH, m), 6. 92(1}1
, t, J = 5Hz), 7. 14-7. 32(
51, I1) Example 24 1-(2-penzylundecanoyl)-4-piperidinyl 3-[N-(2,2,5.5-tetramethyl1
．． 3-Dioxane-4-carbonyl)aminocopropionate React in the same manner as in Example 9 using 1-(2-penzylundecanoyl)-4-hydroxypiperidine instead of 1-oleoyl-4-hydroxypiperidine. The title compound was obtained.

Properties: Oil Molecular weight: 600. 84 Mass spectrometry Calculated value: 600. 4137 Actual value: 6
00. 4122 Optical rotation = [α]2822.6°D (C=1.0, CHC1g)

Claims (1)

[Claims] General formula▲There are numerical formulas, chemical formulas, tables, etc.▼(I) In the formula, R^1 and R^2 are the same or different and each represents a hydrogen atom or a protecting group for a hydroxyl group; R^ 3 represents a C_5 to C_2_5 monovalent aliphatic hydrocarbon group or a group -NH-R^4 which is saturated or unsaturated and optionally substituted with a linear, branched or cyclic aromatic group, Here, R^4 represents a C_5 to C_2_5 monovalent aliphatic hydrocarbon group which is saturated or unsaturated and optionally substituted with a linear, branched or cyclic aromatic group; Either one of Y represents ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and the other represents -O-, -S- or ▲There are mathematical formulas, chemical formulas, tables, etc.▼, where ▲Mathematical formula,
There are chemical formulas, tables, etc. ▼ represents a 4- to 7-membered divalent nitrogen-containing heterocyclic group, R^6 represents a hydrogen atom or a lower alkyl group; m is 0, 1 or 2, n is 1 A compound represented by: an integer of ~4.