Stereodivergent synthesis of 17-alpha and 17-beta-alpharyl steroids: application and biological evaluation of D-ring cortistatin analogues.
One stereocenter makes all the difference: The synthesis and biological evaluation of 17-epi-cortistatin A is reported from a common intermediate used to procure natural cortistatin A. The synthesis features a unique stereocontrolled Raney-Ni reduction process that can be employed to reliably produce both alpha- and beta-configured D-ring aryl steroids. Biological evaluations of these "cortalogs" are reported for the first time.
Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jun
J
Shi
Hiroki
H
Shigehisa
Carlos A
CA
Guerrero
Ryan A
RA
Shenvi
Chuang-Chuang
CC
Li
Phil S
PS
Baran
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D007546:Isoquinolines; D011083:Polycyclic Compounds; D013256:Steroids; C531521:cortistatin A