PROCEDIMIENTO PARA LA OBTENCION DE DERIVADOS DE 17 ALFA- ACETOXI-6-ALFA-CLORO-II BETA - METIL - 19 - NORPREGN - 4 - ENO-3,20-DIONA.

摘要

1,235,742. 11# - Methyl - 19 - norpregnene compounds. G. D. SEARLE & CO. 6 Dec., 1968 [8 Dec., 1967], No. 58044/68. Heading C2U. Novel steroids of the formula (wherein R is H, CHO or C 2-7 alkanoyl; R1 is C 1-7 alkyl; R11 is O or H (#-OH or #-Oacyl), where acyl is C 2-7 alkanoyl; Y is H, Cl or CH 3 ; X is H 2 or, when ring B is saturated and contains no substituent, =CH 2 ; and the #6 double bond is optional) are prepared from 3-alkoxy- 13#-alkyl - 17α- ethyl - 17# - hydroxy - 11#- methylgona - 1,3,5(10) - trienes by known methods. Thus, dehydration to the 17(20)- dehydro compounds, hydroxylation to the 17α,20-diols, Birch reduction to the 2,5(10)- dien-3-enol ethers, hydrolysis to the #4-3-ones and 20-oxidation gives the 17α-hydroxy-#4-3,20- diones which may then be acylated, either by conventional processes which may necessitate hydrolysis of any #3'5-3-enol acylate formed or directly using as acylating agent the complex formed from a metalloid halide, an organic acid halide and a halogenated aliphatic solvent and conducting the reaction in the presence of a lower nitroparaffin of high dielectric constant and under anhydrous conditions. In another process the 20-hydroxy group of the abovementioned 17α,20-diols is oxidized and the resulting 20-ones are ketalized before Birch reduction, after which they may be hydrolysed directly to product 17α-hydroxy-#4-3,20-diones or acylated and then hydrolysed to 17α-acyloxy- #4-3,20-diones. The 16-methylene derivatives are prepared from 3-alkoxy-11#-methyl-19- norpregna - 1,3,5(10),16 - tetraen - 20 - ones by conversion to 16α,17#-pyrazolines, pyrolysis of these to 16-methyl-#16-compounds, peroxidation of these, cleavage of the 16α,17α-epoxides with strong acids to give 16-methylene-17α-ols, and then Birch reducing and hydrolysing these and oxidizing the 20-ol products which may then be 17-acylated. 6-Dehydro compounds are prepared by conversion of the #4-3-ones to #3,5-3- enol ethers and then oxidation of these, e.g. with manganese dioxide reagent or dichlorodicyanobenzoquinone; while 6α-methyl derivatives are prepared by subjecting these enol ethers to the Vilsmeier reagent to afford the corresponding 6-iminium intermediates, hydrolysing these to the 6-formyl compounds, reducing these to the 6-hydroxymethyl compounds, hydrolysing and dehydrogenating to the 6- methylene - #4 - 3 - ones, hydrogenating these to the 6#-methyl compounds and epimerizing these; alternatively the 6-formyl derivatives may be converted directly to the 6α-methyl-#4- 3-ones by reduction and acid treatment. The 6 - methyl - #6 - compounds are prepared from the 6-methylene compounds by isomerization. The 6α-chloro compounds are prepared from the above-mentioned enol ethers by treatment with HOCl or an agent liberating it and epimerization of the 6#-chloro-#4-3-ones thus-produced. The 6 - chloro - #4,6 compounds are prepared (a) by direct dehydrogenation of the 6α-chloro-#4- compounds; or (b) via the 3-enol ethers as described above for the 6-methyl compounds; or (c) by converting the 3-keto-#4,6-compounds to 6α,7α-epoxides, adding on HCl to give the the 6# - chloro - 7α- hydroxy compounds, and dehydrating these. The 3#-ols are prepared by reduction of the 3-ones; they may subsequently be acylated. Starting materials which are racemates may be resolved by standard procedures.