SYNTHESIS OF STEROIDAL [4,6-B,C]-BENZOTHIAZEPINES, A NEW CLASS OF AROMATASE INHIBITOR

Several steroidal [4,6-b,c]benzothiazepines have been prepared via bas e-catalyzed Michael addition of 2-aminothiophenol to 3 beta,17 beta-di acetoxyandrost-4-en-6-one. The product of this reaction has the 4 beta ,5 alpha stereochemistry, but cyclizes to a benzothiazepine with the s teroidal 4 beta,5 beta configuration, confirmed by X-ray crystallograp hic analysis. 2-Aminothiophenol reacts with 3 beta,17 beta-diacetoxyan drost-4-en-6-one under acidic conditions to give a steroidal 6-spiro-b enzothiazole. An androst-4-ene-3,17-dione-based [4,6]benzothiazepine h as been shown to be a moderate competitive inhibitor of the human plac ental aromatase enzyme with IC50 = 42.3 mu M.