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

被引:32
作者
AUDIA, JE
LAWHORN, DE
DEETER, JB
机构
[1] Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis
关键词
ASYMMETRIC AZA-ANNULATION; ENAMINE; STEROID; 5-ALPHA-REDUCTASE; ENZYME INHIBITOR; ALPHA-PHENETHYLAMINE;
D O I
10.1016/S0040-4039(00)61581-2
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The first syntheses of the individual enantiomers of the benzoquinolinone class of selective inhibitors of human Type 1 steroid 5-alpha-reductase are described. For benzoquinolinones lacking an angular substituent, 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 diffraction analysis. The angularly methylated benzoquinolinones are prepared in an enantiospecific (deracemizing) fashion from 1-methyl-6-chloro-2-tetralone in 5 steps, employing a ''formal 3 + 3 aza-annulation'' sequence, with (R) or (S) alpha-phenethylamine as the source of chirality.
引用
收藏
页码:7001 / 7004
页数:4
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