JPS62209095A - Steroid compound and production thereof - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I [R<1> is H, tri 1-7C hydrocarbon or group bonded to oxygen atom of OH to form acetal bond or ester bond; R<2> is H or OR<3> (R<3> is R<1>)]. EXAMPLE:3-beta-Methoxymethoxy-cholesta-5,25-diene-26,23-lactone. USE:An intermediate for synthesizing steroid derivatives vitamin D3 derivative and an antitumor agent. PREPARATION:An alpha-methylene ester shown by formula II [R<11> is R<1>; R<21> is H or OR<31> (R<31> is R<11>); R<41> is (substituted) 1-10C alkyl] is converted into an intermolecular lactone in the presence of an acid catalyst. The prepared compound is optionally deprotected and/or subjected to protection reaction.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel steroid compound having an α-methylene lactone ring and a method for producing the same. More specifically, the present invention provides various steroid derivatives or vitamin D
A steroid compound with a d-methylene lactone ring, which is useful as a synthetic intermediate for 3 derivatives, and which itself has cancer activity and is also useful as a pharmaceutical, and a low-valent compound of flucolene altehydes with a skeletal carbon number of 23. A new production method for producing a steroid compound having an α-methylene lactone ring by carrying out an addition reaction of 2-/·lomethylpbenate esters in the presence of a metal and simultaneously or after the addition reaction, carrying out an intramolecular ring-closing reaction. It is related to.

<Prior Art> Vitamin D metabolites are a group of compounds whose clinical use has been increasing in recent years as therapeutic agents for various diseases. For example, we have recently discovered the metabolite 1α,25-dihydroxy-vitamin D, 26.23-lactone [7 FEBS IJTTER 8, 134,
207-211 (1981)) has a blood calcium lowering effect (Japanese Unexamined Patent Publication No. 118516/1983), an inhibitory effect on tumor cell growth (fP Publication No. 58-210011), and an effect promoting bone formation (Japanese Unexamined Patent Publication No. 60/1989). It has been reported to have pharmacological effects such as -185715), and is expected to be a promising drug.

ld, 25-dihydroxy-vitamin D3-26°23
- As a method for producing lactone, 25-hydroxy-vitamin D, -26,23-lactone (Blochamia try + 18.4775~4
780 (1979)) Method for causing K1 a-hydroxylase to act [FEBS LETTER
8), 134, 207-211 (1981)), isolation method from serum of rats, dogs, etc.
Arch, Biochem, Biophs,
387-391 (1980), Chemical synthesis method of condensing the corresponding A ring skeleton and CD ring skeleton by Wittig reaction [Journal of the Organic Chemistry (J, Org, Chem,), 48
.

4433-4436 (1983)), a chemical synthesis method in which a hydroxylactone ring is introduced into a steroid side chain and then converted into a vitamin D skeleton (Japanese Patent Application Laid-Open No. 130581/1983). However, these methods are not suitable for large-scale synthesis as industrial production methods, or they are not suitable for large-scale synthesis. It takes many steps to obtain the starting material, or even if the starting material is easily obtained, it requires many steps to reach the final product, or it has the same configuration as the natural product (238,25R).
It has drawbacks such as difficulty in selectively synthesizing the body.

<Problems to be solved by the invention> The present inventors have discovered that 1α,25-dihydroxyvitamin D,
As a result of a detailed study on the method for producing -26,23-lactone by chemical synthesis, we found that addition reaction of +2/% lomethylpbenate esters to furfurenaldehydes with 23 carbon atoms in the presence of a low-valent metal was conducted. A steroid compound having a d-methylene lactone ring is obtained by carrying out an intramolecular ring-closing reaction at the same time or after the addition reaction, and by carrying out an intramolecular ring-closing reaction at the same time or after the addition reaction. By doing this, 1m,25-dihydroxyvitamin D,-
The present inventors have discovered that 26,23-lactone can be produced industrially and advantageously, and that steroid compounds having such an α-methylene lactone ring themselves have anticancer activity and are useful as pharmaceuticals. It is something.

Means to solve problems〉 A steroid compound is provided.

In the above formula CI), R1 is a hydrogen atom, tri(Ct~
Cy) represents a hydrocarbon silyl group or a group that forms a Vc7 setal bond or ester bond with the oxygen atom of a hydroxyl group. The tri(C+=Cy) hydrocarbon silyl group is, for example, a trimethylsilyl group.

Tri(C1~) such as t-butyldimethylsilyl group etc.
C4) furkylsilyl group; diphenyl(01-04)alkylsilyl group such as t-butyldiphenylsilyl group; di(C1) such as dimethylphenylsilyl group;
~C4) Alkylphenylsilyl group;)! phenylsilyl group; or tribenzylsilyl group, among which t-butyldimethylsilyl group and trimethylsilyl group are particularly preferred. Examples of groups that form an acetal bond with the oxygen atom of a hydroxyl group include a methoxymethyl group, l-ethoxyethyl group, and 2-methoxyethyl group.
2-propyl group, (2-methoxyethoxy)methyl group t
Benzyloxymethyl group.

Examples include 2-tetrahydropyranyl group and 2-tetrahydrofuranyl group.

Among these, methoxymethyl group and 2-tetrahydropyranyl group are particularly preferred. Examples of groups that form an ester bond with the oxygen atom of a hydroxyl group include aliphatic acyl groups such as formyl group, 7-cetyl group, butyryl group, imbutyryl group, valeryl group, and pivaloyl group; benzoyl group.

Aromatic acyl groups such as p-bromobenzoyl group, 2,4.6-)limethylbenzoyl group, p-phenylbenzoyl group, or methoxycarbonyl group, ethoxycarbonyl group, t-7' toxycarbonyl group, benzyloxycarbonyl group Examples include flukoxycarponyl groups such as. Among these, particularly preferred are 7-cetyl group, benzoyl group, and ethoxycarbonyl group.

In the above formula CI), R2 represents a hydrogen atom or OR', where ρ is the same as or different from R1, and ρ is a hydrogen atom +) II (C1 to C?). Represents a group that forms a monomer bond or an ester bond. )! j (
As the group forming a 7-cetal bond or an ester bond with the C,-C,) hydrocarbon silyl group or the oxygen atom of the hydroxyl group, the same groups as exemplified above for R1 can be mentioned as preferred.

Preferred specific examples of the steroid compound having an α-methylene lactone ring represented by the above formula CI) provided by the present invention include the compounds shown below.

(l) 3β-Hydroxycholesta-5,25-diene-26,23-lactone.

(2) 3β-methoxymethoxy-cholester-5,25-
Diene-26,23-lactone.

+31 3β-ethoxycarbonyl-cholester-5,
25-diene-26,23-lactone.

(4) 1α, 3β-dihydroxy-cholesta-5゜25
- Diene-26,23-lactone.

(5) 1α, 3β-dimethoxymethoxy-cholesta-5
, 25-diene-26,23-lactone.

(6+ 1 d, 3β-jethoxycarboel-
The steroid compound having an α-methylene lactone ring of the present invention, represented by the above formula CI), is represented by the following formula (II), and is In the presence of a catalyst,
Intramolecular lactonization, deprotection and/or
Alternatively, it can be produced by subjecting it to a protection reaction.

The α-methylene ester represented by the above formula (If) is represented by the following formula RIt, as we separately propose.

2-... p-methylpropenoic acid esters represented by the following formula (IV) are added to steroid-23-aldehydes represented by the formula (IV) in the presence of a low-valent metal having reducing power, and if necessary, desorption is performed. Manufactured by protection and/or protection reaction.

In the above formula (IV), X represents chlorine, bromine or iodine, with bromine being particularly preferred.

R41 represents a substituted or unsubstituted alkyl group or a substituted or unsubstituted cycloalkyl group. Examples of substituted or unsubstituted alkyl groups include methyl group!
One ethyl group and one p-vinyl group! Examples include linear or branched groups such as imp p-vinyl group, butyl group, isobutyl group, sa mini-butyl group, tert-butyl group, pentyl group, and hexyl group. Preferred examples of the substituent include a halogen atom, a protected hydroxy group, a nitrile group, and an alkoxycarbonyl group. Examples of the halogen atom include fluorine, chlorine, and bromine, with fluorine or chlorine being particularly preferred. Examples of the alkoxycarbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, and a t-butoxycarbonyl group. Substituted or unsubstituted dichlorofurkyl groups include substituted with the same substituents as mentioned above, or unsubstituted saturated or unsaturated C5 to C5 groups 9 For example, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclooctyl group , cyclodecyl group, etc.

Particularly preferred is an ethyl group, but the group is not limited thereto.

Examples of low-valent metals having reducing power used in the reaction of norkolene aldehydes (11) and 2-halomethylpurbenate a (IV) include zinc, tin, and tin-aluminum.

Magnesium, manganese bismuth, cerium.

Examples include ρum(II) chloride, tin chloride(1), and the like. These metals can be used in the form of powder, or their chlorides can be reduced with lithium aluminum hydride or potassium metal to form v4jIl! in the system. Alternatively, it can be used as a metal amalgam. Particularly preferred are metal tin powder, metal zinc powder, and pm chloride (
1) and chromium chloride (I[) prepared from lithium aluminum hydride can be mentioned Al11? , 2-halomethylpropene modified esters (I
V) and low valence metals are norcholenaldehydes (
IN) 0.8 to 10 equivalents relative to K, particularly preferably 1
~2 tongue amounts are used. The reaction temperature varies depending on the metal used, but is usually -78°C to 80°C, preferably -20°C to 3°C.
0℃.

Particularly preferably a temperature range of 15 to 25°C is employed.

The reaction time is usually about 30 minutes to 3 days, but it is preferable to observe the progress of the reaction by thin layer chromatography or the like.

The reaction is carried out in an organic solvent or in water and a mixed solvent thereof. The solvent used varies depending on the metal used, but any solvent may be used as long as it does not react with the reaction reagent.

Preferably N,N-dimethylformamide.

Examples include N,N-dimethylacetamide, hexamethylene phosphoramide, tetrahydrofuran, and diethyl ether.

The reaction solution thus obtained was post-treated by 1.
It can be purified from K by extraction, washing, drying, concentration, chromatographic separation, recrystallization, etc. At this time, the product C-
The two stereoisomers related to 23 are in a so-called diastereomeric relationship and can be separated from K using column chromatography, heavy liquid column chromatography, and p-mography. The product thus obtained is subjected to protection and/or deprotection reactions as necessary to give α-methylene esters represented by formula (II).

In the above reaction, when the acidity in the reaction system is high, an intramolecular lactonization reaction proceeds following the addition reaction, and a compound having an α-methylene lactone ring represented by the above formula (I) is produced. Sometimes. For example, when zinc dust is used as a low-valent metal, when a large amount of tin chloride (I [l) is used, when the reaction is heated for a long time with an acid such as concentrated hydrochloric acid in the post-treatment of one reaction solution, etc. Some of these will be explained in detail with reference to Examples, but the method for producing a compound having an α-methylene lactone ring from the Norfray/aldehyde represented by the above formula (11) in one step is limited to these. It's not something you can do.

However, under normal reaction conditions, the lactone reaction does not proceed, and α-methylene esters represented by the above formula (It) are obtained.

The thus obtained α-methylene esters represented by the above formula (II) are treated in the presence of an acid catalyst to lead to a steroid compound having an a-methylene lactone ring represented by the above formula CI). I can do it.

Such acid catalysts include organic acids such as para-toluenesulfonic acid, trifluoroacetic acid, and trifluoromethanesulfonic acid; hydrochloric acid.

Inorganic acids such as sulfuric acid; Lewis acids such as trifluoroporane, titanium tetrachloride, etc. can be used. Particularly preferred are para-toluenesulfonic acid, hydrochloric acid, and trifluoroporane, but the present invention is not limited to these. The amount of acid catalyst used is 0.5 to 100 times equivalent, preferably 1 to 5 times equivalent, relative to the raw material compound. Although the reaction temperature varies depending on the acid catalyst used, a temperature range of -78°C to 150°C, preferably 0°C to 50°C is employed. The reaction time varies depending on the acid catalyst used and the reaction temperature, but is about 20 minutes to 24 hours.

The reaction is carried out in the presence of an organic medium or a mixed water-organic medium, and any medium may be used as long as it does not react with the acid catalyst used. For example, when para-toluenesulfonic acid is used as an acid catalyst, methanol and the like can be cited as preferred, and when hydrochloric acid is used as an acid catalyst.

Water-methanol mixed solvent, water-tetrahydrofuran mixed solvent, etc.? It can be mentioned as particularly preferable,
In addition, when trifluoroporane is used as an acid catalyst, anhydrous diethyl ether is particularly preferred. Here, if the hydroxy protecting group of the starting compound (11) is a group that forms an acetal bond, , trifurkylsilyl group, it may be deprotected in any acid-catalyzed reaction. Reprotection, if desired, can be done by well-known methods [e.g.
, Gra@n) , [Pqf rif Ia'・
Protective Groups in Org
anic 5ynthes-1@), John Wiley & Sons (JO) fNWILEY & 5UN
S), 1981). Furthermore, even if the hydroxy protecting group of the starting compound (n) is not deprotected in the reaction with an acid catalyst, it can be deprotected by a well-known method if desired, and further, if desired, re-protected by a well-known method. It can also be protected.

Thus, a steroid compound having an α-methylene lactone ring represented by the above formula CI) is obtained.

On the other hand, by hydrolyzing α-methylene esters represented by the above formula (II) under basic conditions and then reacting with a dehydrating agent, a steroid having a d-methylene lactone ring represented by the above formula CI) can lead to compounds.

Such a hydrolysis reaction can be carried out by a well-known method such as reaction of thorium hydroxide in a mixed solution of water and methanol. The intramolecular dehydration lactonization reaction can be carried out by the action of a dehydrating agent such as dicyclohexylcarbodiimide. Further, after hydrolysis, the intramolecular dehydration and lactonization reaction can also be carried out by heating in a solvent such as benzene in the presence of an acid catalyst. Therefore, α-methylene esters represented by the above formula (IF) can be hydrolyzed into α-
A steroid compound having an α-methylene lactone ring represented by the above formula CI) can also be obtained by a step of converting the methylene carboxylic acid into lactonization.

<Effects of the Invention> The steroid compound having a d-methylene lactone ring represented by the above formula (1) produced by the method described above can be obtained by, for example, performing a type of reaction in which the d-methylene portion is hydrated. , it can be converted into 111.25-dihydroxy-vitamin D,-26,23-lactone by converting the steroid skeleton into the vitamin D skeleton by a known method, and is extremely useful as a synthetic intermediate for vitamin D3-like compounds. be.

Furthermore, it itself has antitumor activity and is expected to be a useful anticancer agent.

As an example of antitumor activity, the above formula C provided in the present invention
A steroid compound having an α-methylene lactone ring represented by I), in which R1゜R1 is a hydrogen atom, the following formula [
The compound represented by the following formula was evaluated for its inhibitory effect on the proliferation of L1210 leukemia cells and was found to have an IC of 1 and a CμI/d.

<Examples> The present invention will be explained in more detail by Examples below, but the present invention is not limited to these examples.

Example 1 Synthetic chromium chloride ([(1269m#8, C+a*oj)
Lithium aluminum hydride (158 ml 4.1 mmoj) was added little by little at 0°C to a suspension of 100 ml in tetrahydrofuran (10 m), and the mixture was heated to room temperature and stirred for 20 minutes.
To this, 3β-methoxymethoxy-24-norcola-5-
Add a solution of en-23-al (779 I2, Cmmol) in tetrahydro7d (tod), followed by the addition of 2-
Ethyl pur-7methylpropenoate (772tnl 4.
U + aao7) was added thereto and stirred at 25°C for 12 hours. The reaction mixture was poured into ice water, 1N hydrochloric acid was added, and the organic matter was extracted with ethyl acetate. The resulting organic layer was diluted with 1N hydrochloric acid. After sequentially washing with brine, drying over anhydrous magnesium sulfate, filtering and concentrating, the crude product was separated from strawberries by silica gel column chromatography (hexane ethyl acetate - 6:1), and the desired product was separated. 23-hydroxy-3β-methoxymethoxy-cholesta-5,25
-0-23-stereoisomer of ethyl diene-26-oic acid, i.e. M A (258 door gO, 5 mmrol
, 25%) and I B (182+aIiU
, 36 txaol, 18%).

Spectral data of n isomers NMR (OD○!ka, δ (ppm); 0.68 (j
3.3H), u, 95(3,3H), 0.6-2.2
(m, 29H), 1.24 (to3H+J-7Hz),
3.25 (3,3H), 3.1-4. tl (wing, 2H)
, 4, C8 (q, 2H, J-7Hz) , 4
．． 52 (3°2H), 5.2 (m, 1 summer (
), 55-47(*H(), 6
．． (J6(d, IH, J=2Hz).

IR (KBr, ct'); 3500. 297
0. 1715. 16301370, 1340.
122t1. 1150. 11!0.1050
1040, 950. 91(1゜M8()'-I9ML/e); 44
(1(M''-OH3U OH20H), 394
273.255° (FD, m/c); 503 (M++1)N
MR (011071, δ (ppm)): 0.6
7 (S, 3H), 0.95 (8, 3H), 0.6-
2.2 (+a, 29H), 1.24 (t, 3H.

J-7Hz), 3.24(8,3H)-3,1-4
,0(m,2H).

4, C9 (q, 2H, J 悶711寞), 4.53 (
1, 2H), 5.2 (comitation).

H), 5.5(1(m, IH), 6.418(
d, H-1, J-2Me).

IR (KBr, ctx”): 3500.2
970. 1715°163 (1,1373,1340
,1226,1150,11101050,1040,
950,910° Example 2 As a starting material, 1α, 3β-di(methoxymethoxy)
The same reaction as in Example 1 was carried out using -24-true-5-cholene-23-al, and 23-hydroxy-1α,
3β-di(methoxymethoxy)-cholester-5,25-
Steric + A injection of ethyl diene-26-oic acid, i.e. go (33%) and ID (24%), (If
, -0HMa(ODOj3.δ(ri1)II)):
U, 71 (8,3H).

1, (10(8,3H), 1.27(1,3)1.J
dust 7Hz).

(1,6-2,5(+a, 26H), 3.34(L
, 3H), 3.37(8,3H), 3.5-4.1
(m, ), 4.19 (q, 2H.

J=7Hz), 4.64(8,2H), 4.64(
q, 2H, J-6Hz) 5.4-5.7 (m+2H),
6.23(d,lH,Jeg2H1)In(neat
cya'): 3suo, 295U+17
1U*1630, 1460. 137 (1,1145
,1100゜1030゜NMIL (ODOj3.δ (ppm)): U, 7
1 (8,3H).

0.99(8,3H)', 1.27(t,3H,J-
7) is).

0.6-2.6 (+a, 26H), 333 (8,3
H), 3.36 (S.

3H), 3.6-4.1(m, 3H), 4.2(1
(q, 2H, J-71(z).

4.63 (S, 2H), 4.63 (q, 211.J=
6Hx), 5.4-5.6(x, 2H), 6.25(
d, IH, J swamp 2H intention).

IR (neat am-1): 3500.
2950. 1?10°1630. 146(1,1
370, 1145, 1100°103tJ.

Implementation row 3 OMO 3βmethoxymethoxy-24-norcola under nitrogen flow
5-en-23-ar (116m10.4mmoj)
and then aluminum F+z powder (8ml, 0
．． 3 mmol) and tin powder (36rnl*0.3ml) were added and stirred at room temperature for 24 hours + lJI.

After adding 2 d of 1N seric acid to the reaction mixture and stirring for 5 minutes, extraction was performed with methylene chloride, and the organic layer was diluted with sodium bicarbonate IJ.
The mixture was washed successively with a solution of sodium hydroxide and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain a crude product. This product was subjected to silica gel column chromatography (hexano
Egul acetate (6:l) and fractionated to give 23-hydroxy-3β-methoxymethoxy-cholesta-5,25-
Stereoisomers of 〇-23 of ethyl diene-26-oic acid MA (14mJi', 9ti) and ■B (181,1
2) was passed down. All of these had spectra that matched those of IB, the dish synthesized in Example v11.

Implementation 914 OMO Same as Example 3, using zinc powder (2 equivalent size) instead of aluminum powder and tin powder, and changing the reaction condition to 60°C.
After 3 hours, 23-hydroxy-3β-methoxymethoxy-cholesta-5,25-diene-26-:t
Ethyl icate A (15%) and l1l (12%)
together with 3β-methoxymethoxy-Frester 5.2
5-diene-26,23-lactone! (21%) was obtained.

Spectral data of f NMR (Opaj3, δppm): 0
．． 68 (S, 3H), (1,95 (8, 3H), (1
, 6-2, 2 (Atsushi, 28H), 3.23 (S, 3H
).

3, (J-3,5 (Otori, IH), 4.2-4.6 (+
a, lH), 4.51 (S.

2H), 5.1-5.3 (T!L, IH), 5.
42 (t, IH, J”2Hz).

6, tJ2 (t, IH, J-2Hz).

T (KBr disc, m'): 29
5 (1,1755,1660+B ti5o, 11θ
0.1030°Fl)-MS; 394(M-01
1,0OH20H) Example 5 Under nitrogen flow, 3β-methoxymethoxy-24-norchola-5-en-23-al (155 mg).

Add tin chloride (fll (100ml, C.53mm
o/), ethyl 2-bromomethyl-propenoate (1
Add 16 mg, (1.6 mmol) and sodium iodide (90 mj', 0.6 mmol) and stir at room temperature for 14 min.
Stir for hours. Furthermore, tin chloride (If) (50+ig
) and ethyl 2-g p-momethylprobenate (40m#
) and stirred at room temperature for 20 hours. Water (
20) was added and the insoluble matter was separated by 3 filtration of Celite, and then 3
The liquid was extracted with diethyl ether. lO% sulfite tsxr
After sequentially washing with thorium aqueous solution and saline solution, drying with anhydrous magnesium sulfate, and after 3 lapses! ! The residue obtained by condensation was subjected to silica gel column chromatography - [8
3β-Methoxymethoxy-Frester 5.25-
Diene-26,23-lactone (58mJL 32'
ir) was obtained. The spectral data matched that of Example 4.

Example 6 23-hydroxy-3β-methoxymethoxy-cholester-5,25-diene-26-oic acid (25 m
, iJ, 0, C5rRmo/ ) of methanol (
To zlgM, rose-toluenesulfonic acid (17m&+
0.1 mmoj) was added thereto, and the mixture was stirred at room temperature for 144 hours.

The reaction mixture was removed under reduced pressure, and the afterglow was analyzed by silica gel column chromatography (1r:ethyl acetate-2:l).
) and the desired 3β-hydroxy-cholester-5,25-en-26゜23-lactone (15m
j', 73chi) was obtained.

NMR(01)Oj,, δppm): U,
67 (S, 3H), 095 (8° 3H), o, s
2-2(me2-2(, 2-43, fJ(m, IH).

4, C-5, C(4,2H), 5.1-5.3(+
a, IH).

IT (KBr disc, cm-”): 340 (
1-3500, 2950°1760, 1660. 1
460. 1430. 138υ, 1350°1280
, 1250. 1140. 1050° Example 7 23-human-oxy-3β-methoxymethoxy-cholester-5=25-diene-26-oinkethyl (25a
6N 11rR111t was added to the tetrahydroflough C2d) M solution of ll + 0, C5mWtoj) and stirred at room temperature for 2 hours. The reaction mixture was neutralized by adding a 1N aqueous sodium chloride solution, and extracted with ethyl 4B acetate. The machine layer is dried with anhydrous magnesium sulfate, 3
Concentrate the remaining amount, extract 1C as in PJ6, and add 3
β-hydroxy-cholesta-5,25-diene-26,
23-lactone (8 ml, 39%) and 3β-methoxycholester-5,25-diene-26,
23-lactone (10 J/, 44%) was obtained. The spectrum of the former (NMR.

1 liter) was consistent with the product of Example 6, and the loser spectrum (MMI'L, I liter) was consistent with the product of Example 4.

Example 8 Under +i4 cord atmosphere, 23-hyI″pxy3β-methoxymethoxy-cholester-5,25-E>ene-26-oic methyle (25vr 1/ r O-05vn
anhydrous diethyl ether (3d) of rn lil)
R solution Vc, add trifluoroborane diethyl complex (~20 mN) at u°C, 11QIlf1 at 0°C, 3 at room temperature.
Stir for hours. The solvent was distilled off under reduced pressure, and the residual sound was prepared in the same manner as Example M 6 to give 3β-hydroxy-cholesta-5,25
-Diene-26,23-lactone (16sF, 78T)
The spectral data were consistent with Example 6.

Example 9 MoMo 23-hydroxy-3β-methoxymethoxy-cholester-5,25-diene-26-oic ethyl C25m
To a methanol (2d) solution of I, IJ, 05 mmol) was added 2N hydroxide solution (l-), and the mixture was stirred at room temperature for 2 hours and 1t6. The reaction mixture was made acidic by adding 5 d of water to the tip of a knife and then 6N salt, and the baby larvae were extracted with ethyl acetate.

The extract was dried over anhydrous magnesium sulfate, and after 3 filtration, it was condensed.
After adding 1 to 2 drops of ft, the mixture was heated under reflux for 1 hour. The solvent was distilled off under reduced pressure, and the product was purified in the same manner as in Example 6 to obtain 3β-methoxymethoxy-cholest-5,25-:)ene-2G.
, 23-lacto7 (8+aII* 35%). The spectral data matched that of Example 4.

Example 10 A hydrolysis reaction was carried out in the same manner as in Example 9. The resulting product was dissolved in methylene chloride (3 liters) and dicyclohexylcarbodiimide (21*I* (1.1 mm)
o]) and N,N-dimethylaminopyridine (2 mJ
j) was added and stirred at room temperature for 10 hours. Remove the solvent under reduced pressure
d was removed, strained and purified in the same manner as in Example 5 to obtain 3β-methoxymethoxy-Frester 5.25-diene-26,2
It attacks 3-lactone (7+a1.31%).

Claims (1)

[Claims] 1. The following formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼……[I] [In the formula, R^1 is a hydrogen atom, a tri(C_1 to C_7) hydrocarbon silyl group or represents a group that forms an acetal bond or an ester bond with the oxygen atom of a hydroxyl group, R^2 represents a hydrogen atom or OR^3, where R^3 is the same as or different from R^1, a hydrogen atom, a tri( C_1 to C_7) Represents a hydrocarbon silyl group or a group that forms an acetal bond or an ester bond with the oxygen atom of a hydroxyl group. ] A steroid compound represented by 2. The steroid compound according to claim 1, wherein R^1 is a group that forms an acetal bond with the oxygen atom of a hydroxyl group. 3. The steroid compound according to claim 1, wherein R^1 is a hydrogen atom. 4. The steroid compound according to any one of claims 1 to 3, wherein R^1 is a hydrogen atom. 5. The steroid according to any one of claims 1 to 3, wherein R^2 is OR^3, where R^3 is a group that forms an acetal bond with the oxygen atom of a hydroxyl group. Compound. 6. The steroid compound according to any one of claims 1 to 3, wherein R^2 is OH. 7. The steroid compound according to any one of claims 1 to 6, wherein the asymmetric center at C-23 has an (R)-sequence. 8. The steroid compound according to any one of claims 1 to 6, wherein the asymmetric center of C-23 has an (S)-sequence. 9. The following formula [II] ▲There are mathematical formulas, chemical formulas, tables, etc.▼...... [II] [In the formula, R^1^1 is a hydrogen atom, tri(C_1~C_
7) Represents a group that forms an acetal bond or ester bond with the oxygen atom of a hydrocarbon silyl group or hydroxyl group, R^2^1 represents a hydrogen atom or OR^3^1, where R^3^1 is R ^
Same as or different from 1^1, hydrogen atom, tri(C_1
~C_7) Represents a hydrocarbon silyl group or a group that forms an acetal bond or an ester bond with the oxygen atom of a hydroxyl group, and R^4^1 is a substituted or unsubstituted C_1 to C
_1_0 represents an alkyl group. ] α-methylene esters represented by are intramolecularly lactonized in the presence of an acid catalyst, and deprotected and/or
or the following formula [I] which is characterized by being subjected to a protection reaction ▲There are mathematical formulas, chemical formulas, tables, etc.▼…………[I] [In the formula, R^1 and R^2 are the same as the above definitions. ]
A method for producing a steroid compound represented by 10. The method for producing a steroid compound according to claim 9, wherein the acid catalyst is p-toluenesulfonic acid, trifluoroborane, or hydrochloric acid. 11. The following formula [III] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼…………………… [III] [In the formula, R^1^2 is a tri(C_1-C_7) hydrocarbon silyl group or an oxygen atom of a hydroxyl group represents a group that forms an acetal bond or an ester bond with R^2^2 is a hydrogen atom or OR^3^
2, where R^3^2 is the same as or different from R^1^2 and represents a tri(C_-C_7) hydrocarbon silyl group or a group that forms an acetal bond or an ester bond with the oxygen atom of a hydroxyl group. ] Steroid-23-aldehydes represented by the following formula [IV] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ...... [IV] [In the formula, X represents ClBr or I, and R^4^1 is substituted or represents an unsubstituted alkyl group, or a substituted or unsubstituted cycloalkyl group. ] 2-halomethylpropenoic acid esters represented by the following formula [II ] ▲There are mathematical formulas, chemical formulas, tables, etc.▼......[II] [In the formula, R^1^1, R^2^1 and R^4^1 are the same as defined above. ] The following formula [I] ▲Mathematical formula, chemical formula, There are tables, etc. ▼ [I] [In the formula, R^1 and R^2 are the same as the above definitions. ]
A method for producing a steroid compound represented by 12. The following formula [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ...... [II] [In the formula, R^1^1, R^2^2 and R^4^1 are the same as the above definitions . ] The following formula [I] ▲ Formula, which is characterized in that α-methylene esters represented by are hydrolyzed under basic conditions, then reacted with a dehydrating agent, and subjected to deprotection and/or protection reactions as necessary. There are chemical formulas, tables, etc. ▼......[I] [In the formula, R^1 and R^2 are the same as defined above. ] A method for producing a steroid compound represented by 13. The following formula [III] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ...... [III] [In the formula, R^1^2 and R^2^2 are the same as the above definitions. ] Steroid-23-aldehydes represented by the following formula [4] ▲ Numerical formulas, chemical formulas, tables, etc. . ]
In the presence of low-valent metals having reducing power, 2-halomethylpropenoic acid esters represented by The following formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼……[I] [In the formula, R^1 and R^2 are the same as the above definitions. ]
A method for producing a steroid compound represented by 14. The production method according to claim 13, wherein the low valence metal having reducing power is zinc. 15. Low-valent metals with reducing power are tin chloride [I
I] The manufacturing method according to claim 13. 16. The manufacturing method according to claim 13, wherein the low valence metal having reducing power is tin or tin-aluminum.