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.
Shi
Jun
J
Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA 92037, USA.
Shigehisa
Hiroki
H
Guerrero
Carlos A
CA
Shenvi
Ryan A
RA
Li
Chuang-Chuang
CC
Baran
Phil S
PS
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