PROCESS FOR PRODUCING STEROID-BRACKET-16-ALPHA,17-B-BRACKET CLOSED-NAPHTALINES

摘要

1512400 16,17-Naphthopregnenes E R SQUIBB & SONS Inc 13 Nov 1975 [25 Nov 1974] 46902/75 Heading C2U The invention comprises #4 and #1'4 steroids of formula wherein R 1 is Cl, F or OH; R1 1 is H; or R 1 and R1 1 together are oxo; R 2 is H or halo; R 3 is H, Me or F; R 4 is H, OH, C 2-7 alkanoyloxy, halo or benzoyloxy (optionally substituted by C 1-6 alkyl, C 1-6 alkoxy or halo); R 5 and R 6 are each H, OH, halo, Ph, CN, CHO, C 1-6 alkyl, C 1-6 alkylthio, C 1-6 alkoxy, C 2-7 carbalkoxy, C 2-7 alkanoyl or C 2-7 alkanoyloxy, with the provisos that (i) when R 6 is H then R 5 is-H, and (ii) when R 5 and R 6 are different then one of them is H; and their preparation from the corresponding 16, 17-unsubstituted #16 steroids or 9,11,16,17-unsubstituted #9(11),16 steroids by reaction with a compound of formula followed by halogenation or hydroxyhalogenation across any 9,11-double bond in the product. Compounds I are interconvertible by (i) hydrolysis of 21-acyloxy; (ii) conversion of 21-OH to 21-halo (e.g. via a 21-mesylate); and (iii) conversion of a 9-bromo-11#-ol via a 9,11- epoxide to a 9-(fluoro or iodo)-11#-ol. Specified intermediates in the above processes are 21 - mesyloxy - 9 - fluoro - 11,21,31,41,- tetrahydro - 11# - hydroxypregna - 1,4 - dieno- [16α,17 - b]naphthalene - 3,20 - dione (Ex. 8): 21 - acetoxy - 41# - ethyl - 6α - fluoro - 11,21,31,41- tetrahydropregna - 1,4,9(11) - trieno[16α,17 - b]- naphthalene - 3,20 - dione (Ex. 25); and 21- acetoxy - 11,21,31,41 - tetrahydro - 41# - phenylpregna - 1,4,9(11) - trieno[16α,17 - b]naphthalene- 3,20-dione (Ex. 26). Compounds I are credited with glucocorticoid and anti-inflammatory activity, and may be made up with carriers into pharmaceutical compositions for oral and topical administration.