Verfahren zur Herstellung von Halogensteroiden

摘要

1,217,530. 4-Chloro-steroids. F. HOFFMANN-LA ROCHE & CO. A.G. 6 Aug., 1968 [7 Aug., 1967], No. 37509/68. Heading C2U. The invention comprises compounds of formula wherein R1 is Cl, F, Br or C 1-8 alkyl; Q is OH or C 1-8 alkanoyloxy; and A represents one of the structures: wherein R2 is H or F; R3 is H, OH, C 1-8 alkoxy, C 1-8 alkanoyloxy, difluoroacetyl, dichloroacetyl, or C 1-8 alkyl; R4 is H, C 1-7 alkylidene or C 1-8 alkyl; or R3 and R4 together form a group of formula R5 is H or C 1-8 alkanoyl; R6 is H, C 1-8 alkyl, or (optically chloro- or bromo-substituted)- mono - unsaturated - C 2-7 - alkenyl or -alkynyl; R7 is H or CH 3 ; R8 is H, F, Cl or Br; R9 is H, OH or a dihydrogen phosphate ester or alkali metal salt thereof, or C 1-8 alkanoyloxy; R10 is H, α-OH, C 1-7 alkylidene, α-Cl, α-F, α-CH 2 Cl, α-CH 2 F, or C 1-8 alkyl; R11 is OH or C 1-8 alkanoyloxy; or R10 and R11 together represent a group of Formula B; or R9 and R11 together represent a group of formula n is 0 or 1; X represents #1-unsaturation or a 2-chloro or 1α,2α-methylene group; X1 and X2 each represent #1-unsaturation or a 2-chloro group (provided that when X1 represents #1- unsaturation, R7 is CH 3 ); Y is CH 2 , CHOH (α or #), or CO; Z is CO, CHOH (α or #), α-(C 1-7 - alkylsulphonyloxy) - methylene, α - (arylsulphonyloxy)-methylene, or (when R8 is H and R9 other than H) CH 2 , or (when R8 is Cl) #- chloromethylene; or Z and R8 together represent #9(11)-unsaturation or a 9,11-oxido group; and the wavy lines denote either the α- or #- configuration. These compounds are prepared by reduction of the corresponding 3-oxosteroids (wherein any 20-oxo group is sterically protected) followed, when necessary, by alkanoylation of the resulting 3-hydroxy compound and/or cleavage of any protecting group. 4,6 - Dichloro - 17α - acetoxy - 16α - methylpregna - 4,6 - diene - 3,20 - dione is prepared by the action of chlorine on 6-chloro-17α-acetoxy- 16α - methyl - pregna - 4,6 - diene - 3,20 - dione. Other 3-oxo starting compounds are described as in Specification 1,215,752. Stearides of Formula I are said to be progestational, androgenic/anabolic, mineralo-cor ticoid and glucocorticoid (i.e. antiinflammatory and thymolytic) agents, and may be made up with carriers into pharmaceutical compositions suitable for oral, parenteral or topical administration.