CS274530B1 - Method of 2-alpha, 3-alpha-dihydroxy- 17 beta-(3-methyl-butyryloxy)-7-oxa-b-homo-5 alpha-androstane-6-on preparation - Google Patents

Abstract

The solution concerns a method of preparation of 2α, 3α-dihydroxy-17-(3-methyl-butyryloxy)-7-oxa-B-homo-5α-androstane-6-one by direct oxidation of 2α, 3α-dihydroxy-17β-(3-methyl-butyryloxy)-5α-androstane-6-one by peroxy acid.

Description

The present invention relates to a novel process for the preparation of 2X, 3'-dihydroxy-17D- (3-methyl-butyryloxy) -7-oxa-β-homo-5'-L-androstan-6-one which affects plant growth in a manner similar to plant hormone brassinolide.

In 1979 (Grove M. D. et al. Nature (London) 281, 216 (1979)), the plant hormone brassinolide was isolated, which affects the division and elongation of plant cells and thus affects plant growth. The accessibility of brassinolide by isolation from plant material is very difficult as it occurs in nature in small quantities. For example, in the rapeseed pollen (Grove M. 0 and spo .: see above), its content is 0.1 ppm, in Chinese cabbage (Morishita T. et al .: Phytochemistry 22, 1051 (1983) / 0.000003 ppm and alike. Also, the accessibility of brassinolide by synthesis is quite difficult due to the complexity of the synthetic procedures and the low yields (for review see, for example, Adam G. et al., Zeitschrift fiir Chemie 27, 41 (1987)).

In the Czechoslovak patent application Czechoslovak. No. 270776 discloses a process for preparing 2-L, 31-dihydroxy-17Q- (3-methyl-butyryloxy) -7-oxa-B-homo-5X.-androstan-6-one of formula I

from compounds of formula II

Wherein R and R are independently of each other a suitable hydroxyl protecting group which can be selectively removed from the molecule in addition to the 17Q- (3-methyl) -butyryloxy group. Compounds of formula (II) above are prepared (U.S. Patent Application Serial No. 270773 and U.S. Patent No. 270,783) from 2X, 3'-dihydroxy-17Q- (3-methyl-butyryloxy) -5X of androstan-6-one of formula III

(III).

CS 274 530 B1

HER

The method of the present invention is characterized in that 2X, 3-dihydroxy-170 (3-methyl-butyryloxy) -7-oxa-β-homo-5α-androstan-6-one of formula I is prepared directly from 2X, 3A- dihydroxy-17B- (3-methyl-butyryloxy) -5A-androstan-6-one of formula III without the need to protect the 2, 3'-diol moiety.

According to the process of the invention, the compound of formula III, after dissolution in a suitable inert solvent, preferably dichloromethane, is oxidized by treatment with a peroxyacid such as m-chloroperbenzoic acid or trifluoroperacetic acid, preferably trifluoroperacetic acid, at room temperature for two to 240 hours. There was thus obtained the desired compound of the formula directly

AND.

The invention is illustrated, but not limited, by way of examples.

EXAMPLE 1 Preparation of 2 ^υ <C, 3a-dihydroxy-178- (3-methyl-butyryloxy) -7-oxa-B-homo-5JC-androstan-6-one (compound I) with m-chloroperbenzoic acid.

To a solution of 2X, 3? -Dihydroxy-17? - (3-methyl-butyryloxy) -5X? Androstan-6-one / Kohout Strnad M .: Coll. Czech. Chem. Commun .: in press; also MS. patent application no. 2707 (compound of formula III; 750 mg) in dichloromethane (75 mL) was added solid m-chloroperbenzoic acid (0.75 g). The mixture was allowed to stand for 10 days at room temperature. The reaction mixture was poured into water, the product was extracted with chloroform, the chloroform layer was separated and washed successively with 10% potassium bicarbonate solution and water. After drying over sodium sulfate, 700 mg of product is obtained, which is purified on a column of 200 g of silica gel, eluting with a chloroform-ether mixture (1: 1 to 1: 2). Treatment of the appropriate fractions yielded 150 mg of pure product, 2X, 3X.-dihydroxy-17- (3-methyl-butyryloxy) -7-oxa-β-homo-5'-androstan-6-one. ¹ H NMT spectrum (60 MHz Tesla Instrument; CDCl 3 + TMS (: 0.82 s, 3H (H-18), 0.91 s, 3H (H-19), 0.95 d, 6H (methyl ester groups)) (J = 6 Hz), 3.50-4.20 m, 2H (H-2B and H-30), 4.04 doublet, 2H (H-7a, J = 5 Hz), 4.58 m, 1H (Η-17Λ, W _1/2 = 18Hz).

IR (carbon tetrachloride) 3445 (OH), 1737, 1728, 1712 and 1189 (ester), 1728, 1712 and 1297 (lactone) cm ^1st For C ^ HHjgOg (422.54) calculated: 68.22% C,

H, 9.06. Found: C, 67.99;

Example. 2

Preparation of 2 '(1,3 H -dihydroxy-170- (3-methyl-butyryloxy) -7-oxa-β-homo-5X-androstan-6-one (compound of formula I) using trifluoroacetic acid.

To a solution of 2X, 3X-dihydroxy-17 '- (3-methyl-butyryloxy) -5j (-androstan-6-one (compound <Formula III, 0.8 g) in dichloromethane (80 mL) was added a solution of trifluoroperacetic acid, prepared of 3.68 ml of trifluoroacetic anhydride, 0.6 ml of at least 50% hydrogen peroxide and 11.6 ml of dichloromethane, the mixture is allowed to stand at room temperature for three hours and then poured (4 to 10% potassium bicarbonate solution). The chloroform layer was separated, washed with water and dried over sodium sulfate, and the solvent was distilled off to give 0.9 g of product which was chromatographed on a silica gel column (200 g), eluting with chloroform: isopropanol (33: 1 to 10: 1). Treatment of the appropriate fractions gave 620 mg of product, which was identical in all respects to the compound prepared above in Example 1. Mass spectrum: m / z 422 (M) ·

Claims (3)

Process for the preparation of 2,3-dihydroxy-17B- (3-methyl-butyryloxy) -7-oxa-8-homo-5-androstan-6-one of formula I Characterized in that 2, 3'-dihydroxy-17B- (3-methyl-butyryloxy) -5-androstan-6-one of formula III 2. 2. 3. 3. oxidized with peroxyacid in an inert organic solvent at room temperature for 2 to 240 hours. The process of claim 1 wherein the inert organic solvent is dichloromethane. 2. A process according to claim 2 wherein the peracid is trifluoroacetic acid.