SYNTHESIS OF THE INDIVIDUAL ENANTIOMERS OF THE BENZOQUINOLINONE HUMANTYPE-1 STEROID 5-ALPHA-REDUCTASE INHIBITORS LY191704 AND LY266111

The first syntheses of the individual enantiomers of the benzoquinolin one class of selective inhibitors of human Type 1 steroid 5-alpha-redu ctase are described. For benzoquinolinones lacking an angular substitu ent, the approach relies upon an enamine acryloyl chloride cyclization followed by non-stereoselective reduction and diastereomer separation . Absolute configuration was established by single crystal x-ray diffr action analysis. The angularly methylated benzoquinolinones are prepar ed in an enantiospecific (deracemizing) fashion from 1-methyl-6-chloro -2-tetralone in 5 steps, employing a ''formal 3 + 3 aza-annulation'' s equence, with (R) or (S) alpha-phenethylamine as the source of chirali ty.