JPH0348650A - Monocyclic terpene derivatives - Google Patents

Abstract

NEW MATERIAL:A compound of formula I (R is H, trimethylsilyl or 1- ethoxyethyl). PREPARATION:2-(1-Methylethyl)-5,9,13-trimethyl-1-trimethylsiloxy-2,4,8 ,12- cyclotetradecatetraene-1-carbonitrile. USE:An intermediate for the whole synthesis of sarcophytol A useful as an anti- carcinogenetic promotor and an anti-cancer agent. EXAMPLE:14-Hydroxy-2-(1-methylethyl)-5,9,13-trimethyl-2,4,8,12-tetrade catetraenoic acid ester is reacted with a halogenating agent or a sulfonic acid anhydride to prepare a compound of formula III [X is halogen or OSO2R<1> (R<1> is alkyl or phenyl)], only whose ester group is reduced and subsequently oxidized to prepare a compound of formula IV. The compound of formula IV is reacted with trimethylsilylnitrile and the prepared compound of formula V is cyclized to provide the compound of formula I.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention provides a novel l-(1-methylethyl)-5゜9.1
It relates to a 3-trimethyl 2.4,8.12-cyclotetradecatetraene-1-carbonitrile derivative. For details, see the anti-carcinogenic promoter effect (Cancer
5urveys, 2540 (1983); Metabolism, v
Concerning a monocyclic terpene derivative that is an important intermediate for the total synthesis of sarcotuitol, which has oρ25 special issue ``Cancer'' 88, 3 (1988)) and antitumor activity [Japanese Patent Application Laid-open No. 56-61317]. It is.

(Prior Art and Problems to be Solved by the Invention) Sarcotuitol A is a sembrene-type macrocyclic diterpene alcohol with a unique structure having four double bonds, including one conjugated double bond, in its 14-membered ring. , its synthesis has not been known until now. Sarcotuitol B of the following formula is the only known synthetic example of Sembren-type diterbenoids (Tetrahedron Letters 1173 (198
9)).

However, this synthesis method produces 1,2-diol and cannot be applied to the synthesis of sarcotuitol A of the following formula.

(Means for Solving the Problems) Therefore, the present inventors have conducted intensive studies on the method for synthesizing sarcotuitol A, and have found that the monocyclic terbene derivative of the present invention is a useful intermediate for the synthesis of sarcotuitol. They discovered this and arrived at the present invention.

The compound of the present invention is represented by the above general formula (I), and specifically includes the following compounds.

Sarcotuitol A Sarcotuitol B That is, the gist of the present invention is the following -format (I) [wherein R represents a hydrogen atom, a trimethylsilyl group or a 1-ethoxyethyl group]. ) exists in the monocyclic terpene derivatives shown.

The present invention will be explained below.

Next, a method for producing the compound of the present invention will be explained.

Among the compounds of the present invention, compounds in which R is a trimethylsilyl group in the general formula (I) can be produced, for example, by the following route.

ゝ1 in ゝ0H (A) (D) (B) \-”X to Y (E) (C) That is, structural formula (B) in the above route (wherein, (R1 represents a 01-C4 lower alkyl group optionally substituted with a halogen atom or a phenyl group optionally substituted with an 01-C4 lower alkyl group.) The compound represented by Known literature (Tetrahedron Letter, 1173 (1)
989)) from 14-hydroxy-2-(l-methylethyl)5゜9.13-trimethyl2.4.8.12-tetradecatetraenoic acid ester (A) without allyl rearrangement of allyl alcohol. How to halogenate,
For example, equivalent to 10 equivalents of carbon tetrahalide
In the presence of an equivalent amount of triphenylphosphine, in an inert solvent such as acetonitrile, or in the case of chlorination, using carbon tetrachloride as a solvent, at a temperature from room temperature to 100°C.
A method of reacting for 8 hours, or a method of reacting an equivalent to 10 equivalents of methanesulfonyl chloride with a metal halide salt, S-collidine, at a temperature of -40°C to room temperature for 1 to 10 hours in a polar aprotic solvent such as dimethylformamide. It can be manufactured by etc.

In addition, for the corresponding compound where X is 108O sulfonic acid chlorides such as methanesulfonyl chloride, valatoluenesulfonyl chloride, and sulfones such as trifluoromethanesulfonic anhydride in the presence of or using pyridine as a solvent at -40°C to room temperature for 1 to 10 hours, equivalent to 10 equivalents It can be produced by using an acid anhydride.

The compound represented by the structural formula (C) (wherein X is as defined above) in the above route is, for example, 14-substituted-2-(1-methylethyl)-5, prepared by the above method,
From 9,13-trimethyl 2,4゜8.12-tetradecatetraenoic acid esters, ether solvents such as ethyl ether and tetrahydrofuran, benzene, toluene,
By reducing only the ester group by a reaction using an equivalent to 10 equivalents of a metal hydride such as dibutylaluminum hydride or a metal complex compound such as lithium aluminum hydride at -70°C to 50°C in a solvent such as hexane or heptane. Can be manufactured.

The compound represented by the structural formula (D) (wherein X is as defined above) in the above route is, for example, 14-substituted-2(1-methylethyl)-5,9,
From 13-trimethyl 2,48.12-tetradecatetraen-1-ol, in a halogen solvent such as methylene chloride or chloroform, a hydrocarbon solvent such as hexane or heptane, or a solvent such as ethyl ether or ethyl acetate, by weight. It can be produced by a method in which an oxidizing agent such as powdered manganese dioxide or barium manganate is applied in an amount of 5 to 20 times the ratio at 0° C. to 50° C. for 1 hour to 50 hours.

Among the compounds represented by the structural formula (E) in the above route (in which R and (]-methylethyl)-5,9,13
-) Limethyl 2,48.12-tetradecatetraenal to 10 equivalents of trimethylsilylnitrile in a catalytic amount of metal cyanide -18- It can be produced by reacting in the presence of a crown-6-ether complex at -20°C to 50°C for 30 minutes to 5 hours, and after dissolving this compound in a solvent such as tetrahydrofuran or methanol, Add a specified aqueous mineral acid solution such as hydrochloric acid or sulfuric acid to 0°
A method of reacting at C to room temperature for 5 minutes to 5 hours, or a method of reacting with a catalytic amount to 10 equivalents of tetraalkylammonium such as tetrabutylammonium fluoride in a solvent such as tetrahydrofuran or dioxane at -20°C to room temperature. Compounds in which R is a hydrogen atom, cyanohydrin derivatives (15-substituted-2-hydroxy 3-(l-methylethyl)-6,10,14-)dimethyl 3,5,9.
13-pentadecatetraenenitrile). The compound represented by R is 1 ethoxyethyl group is prepared from the above cyanohydrin by adding 1 to 10 equivalents of ethyl vinyl ether in a solvent such as ethyl ether or ethyl acetate to a catalytic amount of a mineral acid such as hydrochloric acid or sulfuric acid, or varadruenesulfone. It can be produced by a method such as allowing it to react in the presence of a strong organic acid such as an acid at -20"C to room temperature for 30 minutes to 5 hours.

Among the compounds represented by the structural formula (E) in the above route (in which R and , 10 equivalents of lithium diisopropylamide, hexamethyldisilazane in an ether solvent such as tetrahydrofuran, an aromatic hydrocarbon solvent such as benzene, toluene, or a saturated hydrocarbon solvent such as n-hexane or n-hebutane. Bases such as sodium amide and sodium hydride at -70°C
Among the compounds of the present invention represented by the general formula (I), compounds in which R is a trimethylsilyl group or l-ethoxytyl group can be produced by a method of reacting at 100 ° C. for 5 minutes to 10 hours. , and a method in which an aqueous solution of a mineral acid such as 0.1 to 3N hydrochloric acid or sulfuric acid is allowed to react in a solvent such as tetrahydrofuran or methanol at 0°C to room temperature for 5 minutes to 5 hours, or in a solvent such as tetrahydrofuran or dioxane. Among the compounds of the present invention represented by the general formula (I), R of the compound of the present invention represented by the general formula (I) can be prepared by reacting with a catalytic amount to 10 equivalents of tetraalkylammonium such as tetrabutylammonium fluoride at -20°C to room temperature. Compounds in which is a hydrogen atom can be produced. Sarcophytol A, which is useful as an anti-carcinogenic promoter and an anti-tumor agent, can be derived from the compound of the present invention by the following route.

Route leading to Sarcophytol A (Example) Sarcophytol A That is, among the compounds of the present invention represented by the above-format (r), compounds in which R is a hydrogen atom, such as ethyl ether, ethyl acetate, etc. The ketone body (2-(1-methylethyl)-5,9°13-trimethyl 2, 4,8.12-cyclotetradecatetraen-1-one), which can be converted into ether solvents such as ethyl ether and tetrahydrofuran, aromatic hydrocarbon solvents such as benzene and toluene, or n-hexane. , a metal hydride such as dibutylaluminum hydride or a metal complex compound such as lithium aluminum hydride in a saturated hydrocarbon solvent such as n-heptane at -70'C to 50°C for 5 minutes to 10 equivalents.
Sarcophytol A can be produced by a method of reacting for 5 hours or the like. This route is an industrially advantageous route for the production of sarcophytol A and the compounds of the invention are therefore extremely important synthetic intermediates for that purpose.

The present invention will be explained in more detail with reference to Examples below.
The present invention is not limited by the following examples unless it exceeds the gist thereof.

Reference Example 1 Hydroxyester (14-hydroxy-(1-methylethyl)-5,9,13-)limethyl 2.4,8.1
Ethyl 2-tetradecatetraenoate, 713 mg, 2
．． Triphenylphosphine (787 mg, 3.0
0 mmo/) was added and heated under reflux for 2 hours while stirring, and the disappearance of the raw material was confirmed. After cooling to room temperature, n-hexane was added and insoluble triphenylphosphine oxyto was filtered off, followed by washing with n-hexane. The filtrate and washing liquid were combined and concentrated, and a small amount of n-hexane was added again to remove a trace amount of triphenylphosphine oxyto from the residue obtained.
Filtration and washing were performed. The residue (720 mg, 96%) obtained by concentrating the filtrate and washing solution was the desired 14-chloro-2
-(1-methylethyl)-5゜9.13-)dimethyl 2
, 4.8.12-Tetradecatetraenoate, it could be used as it was in the next reaction without purification.

IR(f i 1m)Cm-'; 2960, 2940,
2870.1?10.1635,1445,1385.
1230.1195.1145.15O NMR (CDCI13, 250MHz) δpp
m; 1.09 (d, J=6.9Hz,
6H,-CH(CHl)2), 1.31 (t,
J=7, IHz, 3H.

-CH,CH,tsu, 1.57. 1.70. 1.80
(e ach bs, each 3H
, -C=CCH,)+1.9-2.2 (m, 8
H, -CH2CHz -), 2゜78 (
hep, J=6.9Hz, IH, CH (CHz
) 2 ), 3.98 (bs, 2H, CHzCj ri.

4.23 (q, J=7.1Hz, 2H, CHt
CHl ), 5.1 (m, I H, -C
=CHCH2-).

5,47 (b t , J = 6.5 Hz
, C=CHCH2).

6.53. 6.54 (each bd,
J=12.0Hz, e a c h I H,
-C=CH-CH=C-) hydroxy ester (14
-Hydroxy-2-(1-methylethyl)-5,9,1
3-) Ethyl dimethyl 2,4,8.12-tetradecatetraenoate, 71.0 mg, 0.20 mmol)
, S-collidine (26.1 mg, 0.22 mrmo
R), lithium chloride (8.5 mg, 0.20 m1
Methanesulfonyl chloride (25.2 mg, 0.22 mmo
n! ) was added. Stirring was continued at the same temperature for 5 hours, and after confirming that the raw materials had disappeared, water and ethyl ether were added, and the organic layer was separated. After washing the organic layer with water, drying (MgS04), and concentrating, the residue obtained was subjected to silica gel column chromatography (n-
14-chloro-2-(l-methylethyl)-
Ethyl 5,9,13-trimethyl 2,4.8.12-tetradecatetraenoate (64.6.86%) was obtained.

Reference Example 3 In an argon atmosphere, ethyl 14-chloro-2-(1 methylethyl)-5,9,13-)limethyl 2°4.8.12-tetradecatetraenoate (670 mg, 1. 81
mmoffi) in 20 ml of dry toluene, cooled on an ethanol-dry ice bath, and mixed with 4 mj of an IMI-toluene solution of diisopropylaluminium dihydride while stirring.
2 was added gradually. After 30 minutes, confirm that the raw material has disappeared.1.
5 nnl of water was added, the bath was removed, and the mixture was thoroughly stirred. Add desiccant (anhydrous magnesium sulfate) and stir further.
The residue obtained by filtration and concentration was subjected to silica gel column chromatography using n-hexane:ethyl acetate (12:
When developing in 1), the alcohol form (14
-chloro-2-(1-methylethyl)-5,9゜13-
Trimethyl 2,4,8.12-tetradecatetraene-
1-ol, 492 mg, 79%) was obtained.

IR(film)cm-';3360,2980,2
940.2890, 1445, 1385, 1265.1
010 1ON (CDC1x, 250MHz) δppm
;1.06 (d, J=6.8Hz, 6H, -C
H(C and)! ), 1.58, 1.70, 1.75
(eachbs, each 3H, -C=CC and,
), 1.9-2.2 (m, 8 H, -CHCf
1L-), 2.47 (hep, J=6.8Hz,
IH, CH (CH: +h).

3.98 <b 3. 2H,-CHCl>,
4.23 (b s, 2 H, -C■, OH), 5.09
(m, IH, -C=C and CHt-), 5.47
(bt, J=6.7Hz, -C=CdanCHz),
6.13.6.16 (each d, J
=12.0Hz, eachIH, -C=CH-C and =C-).

Reference Example 4 Allyl alcohol obtained in Reference Example 3 (14-chloro-2-(1-methylethyl)-5,9°13-trimethyl 2,4,8.12-tetradecatetraen-1-ol Powdered barium manganate (492 mg, 1.51 mmof) in methylene chloride (22 ml) was added.
8.5 g) was added and stirred vigorously under an argon atmosphere. After 8 hours, disappearance of the raw materials was confirmed, and the filtrate and washing liquid obtained by filtration and washing were combined and concentrated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 15
=1) and purification yields the desired 14-chloro-2
-(1-methylethyl)-5,9,13-trimethyl2
．． 4,8.12-tetradecatetraenal (468 g, 95%) was obtained.

TR (film) cm-'; 2970, 2930, 28
80.1670, 1630, 1445, 1390.12
95.1265.1135NMR (CDC/3.250
MH2) δppHl +1.04 (d, J=7
, OHz, 6H, -CH(C,LL) 2 , 1.5
9. 1.70 (each bs, each
3H, -C=CC and ), 1.87 (dJ
=1.3Hz, 3H, -C=CCH), 1.9-2.2
(m, 8H, -C, LLC hill-), 2.89
(hep, J=7.0Hz, IH, -C and (CH3)z
), 3.98 (bs, 2H, -C hill C1).

5.09 (m, L H, C=CHCHz)
, 5.47 (bt, J=6.5Hz, IH, -C
=CHCHz −), 6.82 (d, J=
12.0Hz, IH.

C=C and -CH=C(C,HO)-), 7.11
(d, J=12.0Hz, -C=CH-CH=C(CH
O)-), 10.27 (s, LH, -C and O).

Reference Example 5 The formyl compound (14-chloro-2(1-methylethyl)-5,9,13-trimethyl 2,4,8.
12-tetradecatetraenal, 468 mg, 1.
44 mmo/ ) to trimethylsilylnitrile (0,
25mj! , 1.87 mmo/)? A very small amount of potassium cyanide/18-crown 6-ethyl complex was added while stirring on an ice-water bath under a nitrogen atmosphere. After 2 hours, it was confirmed that the raw material had disappeared, and excess trimethylsilylnitrile was distilled off to give 15-chloro-3-(1-methylethyl)-6,10,14-1-limethyl-2-(
3,5,9,13-pentadecatetraenenitrile (610 mg, quantitative) was obtained.

JR(film)cm-';2960.2930,2
880.2320, 1445, 1255, 1080.8
75,845 NMR (CDC1x, 250MHz) δI'pm
;1, IL 1.15 (each d, J=6
．． 9Hz.

each 3H,-CH(C and,)z), 1
．． 60°1.71, 1.77 (each s, e
ach 3) (.

-C=CC and ), 1.9-2゜2 (m, 8H,
-C and C and) , 2.64 (hep, J=6.9
Hz.

IH, -CdanCCHs)z), 3.99
(s, IH.

C and 1CIl), 5.11 (m, IH, -C=C
HCH2-), 5.33 (S, IH, -CHCN).

5.48 (bt, J=6.5Hz, IH, -C=CH
CH2-), 6.04.6.25 (each d,
J=11.3Hz, each and=C-).

Reference Example 6 IH, -C-C and -C 15-chloro-3-(1-methylethyl)-6,10,14-1-dimethyl-2-trimethylsiloxy 3,5,9 obtained in Reference Example 5 A solution of 13-pentadecatetraenenitrile (58 mg, 0.14 mn+oj2) in tetrahydrofuran (2 mg) was cooled to 0°C, and IN hydrochloric acid (0.5 ml) was slowly added dropwise.

After stirring at this temperature for 10 minutes, saturated brine (5 mJ) was added and extracted with ether (10 ml x 2).

The organic layer was washed with saturated brine (5 mj) and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = lO:1). Then, 15-chloro-2-hydroxy-3-(1-methylethyl)-6,1
0,14-trimethyl 3,5.9.13-pentadecatetraenenitrile (38 mg, 75%) was obtained.

IR (film) cm-'; 3450, 2960, 29
30.28?5,2860,2320,1650.14
45.13B5.1265.1020.93O NMR (CD Cis, 250 MHz) δ991
1;1.14.1.28 (each d, J=
6.8Hz.

each 3H,CH(CIL)'z),
1.59°1.71,1.79 (each s, e
ach 3H.

C=CCHx), 1,90 2.20 (m, 8H.

-C and C and w-), 2.27 (d, J
=5.5Hz.

IH, OH), 2.62 (hep, J=6.8Hz.

1 Hl CjllLL (CH3n z),
3.99 (s, 2H.

CHz C1), 5.09 (m, LH, C=
CHCH2), 5.29 (d, J=5.5
Hz, IH.

CHCN), 5.48 (brt, J-6:
4Hz, LH, -C=CHCH2-), 6.1
4.6.34 (each d, J=11.4
．． 11.5Hz, eachIH, -C=CH-C
and=C-).

Reference Example 7 15-chloro-2-hydroxy-3-(l-methylethyl)-6,10,14-)limethyl 3°5.9.13-
Pentadecatetraenenitrile (204B, 0.5
6111mog) and ethyl vinyl ether (100
μj! , 0.96 n+a+ojl in dichloromethane (5 mf) was added with a very small amount of para-toluenesulfonic acid while stirring on ice water under a nitrogen atmosphere. After 10 minutes, saturated aqueous sodium bicarbonate solution (15 mA) and n
Add 20 ml of -hexane-ether (1:1) solution, separate the organic layer, and add the aqueous layer to n-hexane-ether (1:1).
: 1) Extracted several times with 20 ml of solution. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate-20:1) to give 15-chloro-2-(1 -ethoxyethoxy)3-(l-methylethyl)-6,10,14-trimethyl3.5,9.1
3-Pentadecatetraenenitrile (207mg,
85%) was obtained.

IR (f j 1 m) cm-'; 2960, 2930.
1445 1385.1262, 1140.1080.
1050.1020.930°NMR (CDClz,
250 MHz) δppm; 1.06-1
．． 25 (m, 9H, Cf1LCHz O, CH (C
H2)t), 1.35. 1.38 (ea
chd, J=5.5, 7.9Hz, 3H, Cdan, CHO
).

1.58. 1.70. 1.77 (each
s, each 3H, C=CCH3), 1,
90 2.30 (m, 8 H, CHZ CHZ
), 2.60 (h ep, J=
6.8H2,'IH,CH(CH3)z).

3.45 3.74 (m, 2H,0CHt
CHs).

3.98 (s, 2H, CHz C1”)
, 4.77. 4.99 (each q,
J=5.5Hz, LH,0CHCHs)
, 5.10 (b r s, I H, C=
CH-CHz-), 5.29. 5.34 (e
ach s, LH, CHCN), 6.09
(d, J=11.4Hz.

LH, -C=CH-CH=C-), 6.32. 6
．． 35 (each d, J=11.4Hz
, IH, -C-CH-CH=C-).

Example 1 Sodium amide of hexamethyldisilazane (217m
g, 1.18 m+wol) of dry tetrahydrofuran solution (5.5 mj) was heated at 40°C under an argon atmosphere.
cyanohydrin trimethylsilyl ether (15-chloro-3-(1-methylethyl)-6,10,14-)dimethyl-2-trimethylsiloxy 3,5,9.13 -Pentadecatetraenenitrile 100+wg.

0.23 wmol) of dry tetrahydrofuran solution (4
, 5 mJ) was added dropwise over a period of 15 minutes. After stirring at this temperature for 15 minutes, a saturated aqueous ammonium chloride solution was added while stirring on an ice-water bath to stop the reaction.

After distilling off tetrahydrofuran under reduced pressure, the organic matter was extracted with ether, and the resulting residue was subjected to silica gel column chromatography (n-hexane:ethyl acetate-60:1) to obtain 2-
(1-methylethyl)-5゜9.13-trimethyl-1
-trimethylsiloxy 2.4,8.12-cyclotetradecatetraene-1-carbonitrile (24.6 mg,
27%) and 2-(1-methylethyl)-5,9,1
3-) trimethyl 2,4,8.12-cyclotetradecatetraen-1-one (16.6 mg, 24%) was obtained.

Below, NM of 2-(1-methylethyl)-5,913-trimethyl-1-trimethylsiloxy 2゜4.8.12-cyclotetradecatetraene-1-carbonitrile
Indicates R.

NMR (CDC13, 250MHz) δpp+n
;0.23 (s, 9H, -3i (CH:1)
3), 1.09.1.15 (each d, J=
6.7Hz, each 3H, -CH(CHt)z
), 1.50.1°62 (each bs, e
ach 3H, -C-CCHs), 1.70 (d
, J=1.3Hz, 3H.

C=CCHx), 2.02.2 (m, 8H,
-CHt CHt ), 2.51 (hep, J=
6.7Hz.

IH, -CH(CH3)z), 2.55.2.65(
each d, J=14.2Hz, eac
hIH, -CH, Hb CN-), 4.94 (b
t, J=6.1Hz, IH,C=CHCHz
), 5.15 (bt, J=5.6Hz, IH,
-C=CHCHz), 6.1? , 6.44 (
each d, J=11.8Hz, each
IH, -C=CH-CH=C-).

Example 2 Lithium amide of ctos hexamethyldisilazane (205 mg
A dry hexane-benzene solution (1:4.5mff1) of cyanohydrin ethoxyethyl ether (15-chloro-2-(1-ethoxyethoxy )-3-
(1-methylethyl)-6,10,14-trimethyl3
,5,9.13-pentadecatetraenenitrile (11
A dry benzene solution (6 ml) of 5 mg, 0.26 mmol) was added dropwise over 20 minutes. After stirring at this temperature for 5 minutes, a saturated aqueous ammonium chloride solution was added while stirring on an ice-water bath. The organic layer was dissolved in ether (20 mjl:
After extraction with
゜13-Trimethyl 2,4,8.12-cyclotetradecatetraene-1-carbonitrile (51.6 mg).

50%) was obtained as a mixture of diastereomers.

When this was subjected to silica gel column chromatography (n-hexane:ether=20:1), one isomer represented by the above structural formula was obtained.

IR(f i 1m) cm-'; 2975. 29
40°1450, 1385. 1140. 1025
．． 940°NMR (CD Cis, 250 MHz)
δppm; 1.10. 1.14 (each
d, J = 6.7Hz.

each 3H, CH(CH+)z)1.22
(t.

J=7°IH,,3H,CH,C hill 0)).

1.28 (d, J=5.4Hz 3H, CH3
CHO).

1.49. 1.6B, 1.71 (each
s, each3H, CH3C=C), 1,95
2.28 (m.

8H, CHz C=C), 2.60 (hep,
IH, J=6.1Hz, CH(CH3)z),
2.72°2.89 (each d, J=14
．． 7Hz.

each IH, C and CH, CCN), 3.58 (
q, J=1.1 Hz, 2 H, 0 CHz CH
3).

4.89 (q, J=5.4Hz, IH, -0C
H-CH,), 4.86-5.00, 5.06-5.1
8 (each m, each IH, -CH
-CH.

), 6.28 (brs, 2H, -C=CH-C
H=C-).

Example 3 czus 1-(1-ethoxyethoxy)-2-(1-methylethyl)-5,9,13-trimethyl 2.4°8.12-cyclotetradecatetraene-1-carbonitrile (31
, 8 mg, 0.08 n+mof) in methanol (3 mA) was stirred on an ice-water bath and a very small amount of para-toluenesulfonic acid was added. After stirring at this temperature for 1 hour,
A saturated aqueous sodium chloride solution (3 mL) was added and extracted with ether (10 mL x 2). The solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel column chromatography [n
-Hexane:ethyl acetate=7=1) to purify 2-(
l-methylethyl)-5,9,13-trimethyl2,4
, 8.12-cyclotetradecatetraene-1τ carbonitrile (13.7 mg, 60%) was obtained.

NMR (CDCA3, 250MHz) δppfl;
1.15, 1.19 (each d, J=6.7H
z.

each 3H, CH(CH3)2 ), 1.55°1.63, 1.69 (each s, each
3H.

CH3C=C), 1.94 2.35 (m, 8H
.

CHz -c==c-), 2.51 (hep,
J=6.7Hz, IH, CH(CHs)z), 2
．． 66.2.73 (each d, J=14.1H
z, 2H, CH.

Hb CCN), 2.89 (brs, IH, OH)
, 4゜93.5.24 (each brt, J=5
．． 3Hz.

e a c h I H, -C=CH-CHz -)
, 6.22.6.42 (each d J
=11.1Hz, each IH, -C=CH-CH
=C-).

Example 4 ゝ6Yゝcx Alcohol (14-chloro-2-(1-methylethyl)-5,9,13-trimethyl 2.4゜8.12-tetradecatetraen-1-ol.

Powdered barium manganate (6.5 g) was added to a solution of 453 mg, 1.66 mmoffi) in methylene chloride (25 rnffi) under an argon atmosphere, and the mixture was stirred at room temperature for 24 hours. The methylene chloride solution obtained by filtration and washing was concentrated under reduced pressure, and the residue (crude formyl compound) was dissolved in trimethylsilylnitrile (0.29mj2.2.16mm) under a nitrogen atmosphere.
of) and a very small amount of potassium cyanide/18 crown 6-ether complex was added while stirring on an ice-water bath. After 2 hours, excess trimethylsilylnitrile was distilled off to obtain a residue (563 .mu.).

A dry tetrahydrofuran solution (22 mf) of this crude cyanohydrin ether was added at 50-52 mf under an argon atmosphere.
1M of lithium bis(trimethylsilyl)amide at °C
4.0 mj2 of the tetrahydrofuran solution was gradually added dropwise over 35 minutes to a solution diluted with dry tetrahydrofuran (22 mj). Immediately after the dropwise addition, the tetrahydrofuran was distilled off under reduced pressure, and the residue was mixed with ethyl ether and cold IN.
It was dissolved in an aqueous hydrochloric acid solution (30mffi). The residue obtained by washing the ether layer with water, drying (MgSO4) and concentrating was subjected to silica gel chromatography (developing solution: n-hexane:ethyl acetate = 30:1) to obtain the desired 2-(1-methylethyl)-5, 9,13-)dimethyl-1-trimethylsiloquine 2,4,8.12-cyclotetradecatetraene-
1-Carbonitrile (330.64% (total from alcohol)) was obtained.

Reference Example 8 Cyanohydrin (l-hydroxy-2-(1 methylethyl)-5,9,13-trimethyl 2゜4.8.12-
Cyclotetradecatetraenecarbonitrile (78,0
mg, 0.25 mmoffi) in ethyl ether 4
ml and stirred for 10 minutes with 2 ml of saturated aqueous sodium bicarbonate solution on an ice-water bath under a nitrogen atmosphere. After confirming the disappearance of the raw materials, the organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated. The resulting residue was subjected to silica gel column chromatography (developing solvent: n-hexane: ethyl acetate - 7:1), Target 2-[1-methylethyl)-5,9,13-)limethyl 2.4.8°12-cyclotetradecatetraen-1-one (58.0 mg, 7
5%).

Reference Example 9 Under argon atmosphere, ketone body (2-(1-methylethyl)-5,9,13-)limethyl 2,4°8.12-cyclotetradecatetraen-1-one, 131 mg,
0.6 ml of a 1 M toluene solution of diisobutylaluminum hydride was added to a solution of 0.48 mmof) in 2.5 ml of dry toluene while stirring on a -70°C refrigerant bath.
1 was added dropwise. After 1 hour, the disappearance of the raw material was confirmed, and 0.2
5 ml of water was added, the bath was removed, and the mixture was stirred well. After drying over anhydrous magnesium sulfate, stirring, filtering, and concentrating, the resulting residue was purified by silica gel column chromatography (developing solvent, n-hexane:ethyl acetate = 12:1) to obtain the desired sarcotuitol A ( 125mg, 88
%) was obtained.

Applicant: Mitsubishi Kasei Corporation

Claims (1)

[Claims] (1) The following general formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. are included ▼... (I) [In the formula, R represents a hydrogen atom, a trimethylsilyl group, or a 1-ethoxyethyl group. ) is a monocyclic terpene derivative.