JPH07116217B2 - Method for producing steroid compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing a steroid compound useful as an intermediate for a brassinolide analog which is a plant growth regulator.

[Conventional technology]

formula A compound which is an intermediate of a brassinolide analog using the compound represented by As a method for producing the steroid compound represented by,
The method of JP-A-61-69790 is known.

[Problems to be solved by the invention]

As in the method described in JP-A-61-69790, chromic anhydride (Jones reagent) has been frequently used as an oxidizing agent in sulfuric acid, but the reaction is carried out in a strong acid using toxic hexavalent chromium. Therefore, there is a disadvantage that a protective group cannot be used, and it cannot be said to be advantageous when it is carried out industrially.

Therefore, the present inventor has conducted earnest studies to find an oxidation method that does not use strong acid or chromium.

[Means for solving problems]

The inventor (Where R ₁ , R ₂ represents a methyl group or an ethyl group, and * represents a group R ₁
The binding site to the steroid nucleus of) is used as a starting material, and various oxidation conditions have been investigated. We have found a method by which the compound shown by can be prepared without using Jones reagent.

The present invention will be described in detail below.

The compound of formula (1) can be oxidized with an N-halocarboxylic acid amide in the presence of a quaternary ammonium halide salt in a suitable solvent to obtain the desired compound of formula (2).

In this reaction, examples of the quaternary ammonium halide include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium iodide, benzyltriethylammonium chloride, benzyltriethylammonium bromide and iodide. Benzyltriethylammonium, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide,
Examples thereof include benzyltrimethylammonium iodide, and among them, tetra-n-butylammonium iodide is particularly preferable. The amount of these salts is the amount of compound 1 of formula (1)
It is preferable to use 1.0 to 5.0 mol per mol.

Examples of the N-halocarboxylic acid amide that can be used as an oxidizing agent include N-bromosuccinimide, N-iodosuccinimide, N-bromophthalimide, N-iodophthalimide, N-bromoacetamide, N-iodoacetamide, and N-bromo. Examples thereof include caprolactam and N-iodocaprolactam, and these are preferably used in an amount of 2 to 10 mol per mol of the compound of the formula (1).

Next, as the solvent, aliphatic or aromatic hydrocarbons, for example, methylene chloride, chloroform, carbon tetrachloride, 1,2-
Examples thereof include dichloroethane, 1,1,1-trichloroethane, trichloroethylene, tetrachloroethylene, n-hexane, benzene, toluene, xylene, monochlorobenzene and dichlorobenzene.

The reaction temperature is preferably from room temperature to around the boiling point of the solvent.

〔The invention's effect〕

According to the method of the present invention, the compound of formula (1) is used as a starting material, and the desired compound of formula (2) does not use a strong acid or a toxic hexavalent chromium compound, and further, it is not necessary to lower the reaction temperature. Moreover, since the production can be performed at a yield of 90% or more, it can be industrially sufficiently implemented.

〔Example〕

 The present invention will be described below with reference to examples.

Example 1. (22E, 24R) -3α, 5-Cyclo-5α-ergost-22-en
Synthesis of -6-one: 1.13 g (5 mmol) of N-iodosuccinimide and 0.37 g (1 mmol) of tetra-n-butylammonium iodide were melted in 10 ml of methylene chloride and then added to i-brasscasterol.
A 0.40 g (1 mmol) solution of methylene chloride in 3 ml was added dropwise, and the mixture was reacted at room temperature for 10 hours or at 40 ° C. for 3 hours, and then 20 ml of a saturated aqueous solution of sodium thiosulfate was added to separate the methylene chloride layer, and saturated It was washed with brine and dried over sodium sulfate. After evaporating the solvent under reduced pressure, the crude product was purified by silica gel column chromatography (eluent n-hexane-ethyl acetate) to obtain the desired (22E, 24R) -3α, 5-C.
yclo-5α-ergost-22-en-6-one 0.38 g (yield 96
%).

mp 107-109 ° C (literature value ¹⁾ mp 108-110 ° C IR: 1680cm ^-1 (νc = o) NMR: δ 0.73 (s, 3H, 18-CH ₃ ) 1.01 (s, 3H, 19-CH ₃ ) 5.1-5.3 (m, 2H, 22- and 23-H) Reference ¹⁾ MJThompson et al., Steroids, 7 , 745 (1965) Example 2. 24S-Ethy1-3α, 5-Cyclo-5α-Cholest- 22E-en
Synthesis of -6-one: From 0.41 g (1 mmol) of i-stigmasterol to Example 1
The reaction was conducted in the same manner as in (1) and the product was purified by a silica gel column to obtain 0.38 g (yield 92.5%) of the desired ketone.

mp 106-107 ℃ (reference value ²⁾ mp 102-103 ℃ IR: 1675cm ^-1 (νc = o) Reference ²⁾ K.Mori et al., Tetrahedron, 38 , 2099 (1982) Example 3 N-iodophthalate 1.37 g (5 mmol) of acid imide and 0.37 g (1 mmol) of tetra-n-butylammonium iodide were dissolved in 10 ml of methylene chloride, and a solution of 0.40 g (1 mmol) of i-brasscasterol in 3 ml of methylene chloride was added dropwise thereto. The reaction, post-treatment and purification by silica gel column chromatography were carried out in the same manner as in Example 1 to obtain (22E, 24R) -3α, 5-Cyclo-5α-er.
0.38 g of gost-22-en-6-one was obtained.

Continuation of front page (56) Reference JP-A-56-161384 (JP, A) J. Chem. Soc. Chem. Commun No. 18 (1984) P, 1236-1238 J. Chem. Soc. Perkin Trans I No. 2 (1983) P. 383-386 J. Chem. Soc. Perkin Trans I No. 2 (1983) P. 379-382 Chem. Pharm. Bull. Vol. 30, No. 11 (1982) P. 4181-4185 Tetrahedron Vol. 38, No. 14 (1982) P. 2099-2109 Steroids Vol. 38, No. 5 (1981) P. 567-580 Agric. Biol. Chem. Vol. 45, No. 11 (1981) P. 2579-2585

Claims (1)

[Claims] 1. A formula (In the formula, R ₁ is R ₂ represents a methyl group or an ethyl group, and * represents a binding site of the group R _{1 to} the steroid nucleus. ) Is oxidized with a N-halocarboxylic acid amide in a halogenated hydrocarbon solvent in the presence of a quaternary ammonium halide. (Wherein R ₁ has the same meaning as described above).