Novel 17 alpha-chloro-17 beta-sulfinyl steroids as specific inhibitors of sebaceous gland activity: potential antiacne agents.

The preparation and antisebaceous gland activities of a series of 17 alpha-chloro-17 beta-sulfinyl steroids are described. They were obtained from the corresponding 17 alpha-sulfides by chlorination and oxidation with iodobenzene dichloride in aqueous pyridine at -40 degrees C. A single-crystal X-ray structure determination of 17 alpha-chloro-17 beta-(benzylsulfinyl)-1,4-androstadiene-3,11-dione (4) established the absolute configuration at sulfur to be R. From an analysis of their CD spectra, some of the other alpha-chloro sulfoxides were also assigned the same absolute stereochemistry at sulfur. Inhibition of sebaceous gland activity, after topical application of the test compounds, was determined in hamsters and found to reach a maximum with 4. The 17 beta-sulfone and 17 alpha-sulfide corresponding to 4 were less potent. Subcutaneous administration of 4 produced no antiandrogenic effects in either hamsters or rats.

Preparation and progestational activity of 6-cyano-16-methylene-17 -hydroxy-4,6-pregnadiene-3,20-dione 17-acetate and related compounds.

PIP: The synthesis of of 6-formyl-6-dehydro-16-methylene-17alpha-acetoxyprogesterone (3) and of 6-cyano-6-dehydro-16-methylene-17alpha-acetoxyprogesterone (4) is reported. The preparation of (3) was carried out by converting 3-ethoxy-16-methylene-17alpha-YDROXY-3,5PREGNADIEN-20-ONE 17-acetate (5) by the Vilsmeier reaction to 3-ethoxy-6-formyl-16-methylene-17alpha-hydroxy-3,5-pregnadien-20-one 17-acetate (6). On treatment with dichlorodicyanobenzoquinone (DDQ) in 95% aqueous acetone (6) afforded the desired (3) in 45% yield. The 6-cyano derivative (4) was prepared by reacting (6) with hydroxylamine to give 3-ethoxy-6-oximinomethyl-16-methylene-17alpha-hydroxy-3, 5-pregnadien-20-one 17-acetate; this compound on treatment with DDQ in 95% aqueous acetone gave 6-oximinomethyl-16-methylene-17alpha-hydroxy-4, 6-pregnadien-3,20-dione 17-acetate (9) in 68% yield. Reaction of (9) with phosphorus oxychloride in pyridine afforded the desired 6-cyano dienone (4) in 70% yield. Progestational activity of (3) was the same as that of progesterone, while that of (4) was 5.8 as great.^ieng