Synthesis of 7-Epi +-FR900482: an epimer of comparable anti-cancer activity.
FR900482 is a potent anti-tumor therapeutic that has been investigated as a replacement candidate for the clinically useful Mitomycin C. Herein, we report synthesis and biological testing of 7-Epi (+)-FR900482, which demonstrates equal potency relative to the natural product against several cancer cell lines. Highlights of this work include utilization of our palladium-catalyzed DYKAT methodology and development of a Polonovski oxidative ring expansion strategy to yield this equipotent epimer in 23 linear steps.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. mbtrost@stanford.edu
O'Boyle
Brendan M
BM
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
C529541:7-epi-FR900482; D000970:Antineoplastic Agents; D010078:Oxazines; C053335:FR 900482