The method of producing sidaction

 

(57) Abstract:

The invention relates to the synthesis of biologically active substances, in particular to the synthesis of ecdysteroids, specifically to the synthesis of SIDACTION found in very small amounts in some species, for example Blehnum niponicum and Vitex canescens. The method is realized by the interaction of the 20-hydroxyecdysone (1) c triperoxonane anhydride. Under the action of a suspension of the compound (1) in chloroform three times molar excess of the reagent, after 30 min was observed homogenization of the reaction mixture, after evaporation of which the chromatography was carried out was selected SIDACTION with the release of 42%. The method is simple to perform and gives a higher yield of the target product.

The invention relates to the synthesis of biologically active substances, in particular to the synthesis of ecdysteroids, specifically to the synthesis of SIDACTION found in very small amounts in some species, for example Blehnum niponicum [Takemoto, T. Okuyama, S. Arihara, Y. and H. Hikino Hikino. Chem. Pharm. Bull., 1969, 17, 1973] and Vitex canescens [A. Suksamrarn, N. Promrangsan, Century Chitkul, S. Homvisasevonsa and A. Sirikate. Ecdysteroids of the root bark of Vitex caescens. // Phytochemistry, 1997, 45, 6 1149-1152].

Ecdysteroids are widely distributed in the animal and vegetable world and perform the function regulator analogues are of interest to medicine. Recently in this regard, there is a considerable interest derived ecdysteroids with a heterocycle in a side chain, some of which are expected, in particular, antitumor activity. Know about getting SIDACTION semisodium synthesis (22,25-anhydrous-20-hydroxyecdysone) [Roussel P. G., Turner N. J., Dinan L. N. Synthesis of Shidasterone and the Unambiguous Determination of its Configuration at C-22//J. Chem. Soc. , Chem. Commun. , 1995, 933-934.] 20-hydroxyecdysone. When interacting 20-hydroxyecdysone 1 with phenylboric acid in a medium of dimethylformamide (DMF) was obtained 20,22-phenylboronate-20-hydroxyecdysone 2. In the interaction of compound 2 with acetone in the presence of 2,2-dimethoxypropane (DMP) and TsOH was obtained 2,3-acetonide-20,22-phenylboronate-20-hydroxyecdysone 3. Treatment of compound 3 in a 30% solution of hydrogen peroxide in the alkaline environment of tetrahydrofuran led to selective removal boronates protection with obtaining 2,3-monoacetate 4, the total output of which amounted to 65%. Interaction acetonide 4 methylchloride in the presence of (i-Pr)2NEt in dichloromethane was obtained (22/R)-mesilate 5 (50%). Under the action of dry KF or anhydrous acetonitrile (tetrabutylammonium fluoride (F)) in THF mesilate 5 was converted into 20R,22S-epoxide 6 (50%). Effect on connection 6 targetrate of triethylamine n is from 8 to exit 91%, identical to natural object (scheme 1).

The disadvantages of this synthesis is a multi-stage, the use of specific reagents, incomplete conversion of the starting reagents at each stage, which requires additional separation, the low yield of the final product (about 10%).

The aim of the invention is to simplify the way with a simultaneous increase in the yield of the final product.

A distinctive feature of the proposed method, which allows to solve tasks, is the use of triperoxonane anhydride (TFW) as a dehydrating agent. When studying the interaction of 20-hydroxyecdysone (1) with TFW we found that under the action of a suspension of compound 1 in chloroform three times molar excess of the reagent after 30 min was observed homogenization of the reaction mixture, after evaporation of which the chromatography was carried out was allocated 22,25-anhydrous-20-hydroxyecdysone (8) with the release of 42%, identical (IR, UV, NMR1H and13(C) SIDACTION obtained in the above-mentioned 7-stage synthesis [Roussel P. O., V. Sik, Turner N. J. and Dinan L. N. Synthesis and biological activity of side-chain analogues of ecdysone and 20-hydroxyecdysone//J. Chem. Soc., Perkin Trans. 1, 1997, 2237].

Bore which opens the way to the final product and provides a higher yield of the final product (42%) in comparison with the known.

The synthesis is carried out as follows.

An example of the method. A mixture of 0.53 g (2.49 mmol) of TFW and 0.4 g (0.83 mmol) of 1 in 5 ml SNS3(scheme 2) stirred 30 min at room temperature (up to homogenization of the reaction mixture). The reaction mass was evaporated, the residue was chromatographically on a column with SiO2(eluent l3-Meon, 5:1) with 0.17 g of SIDACTION (22,25-anhydrous-20-hydroxyecdysone but also or (20R, 22R)-22,25-anhydrous-2, 3, 14, 20 tetrahydroxy-5-cholesterol-7-EN-6-she (8)).

The method of producing SIDACTION of 20-hydroxyecdysone but also characterized in that 20-hydroxyecdysone is subjected to interaction with triperoxonane anhydride, taken in a 3-molar excess in the environment of chloroform at room temperature for 30 minutes

 

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