Review of cytotoxic cephalostatins and ritterazines: isolation and synthesis.
The cephalostatins and ritterazines comprise a family of structurally related natural products reported by Professors G. R. Pettit and N. Fusetani from 1988 -1998. Isolated from the invertebrate marine chordates Cephalodiscus gilchristi and Ritterella tokioka, the cephalostatins and ritterazines exhibit potent cytotoxicity toward the murine P388 lymphocytic leukemia cell line. In fact, cephalostatin 1 ( 1, ED 50 0.1-0.001 pM) proved to be one of the most powerful cancer cell growth inhibitors ever tested by the U.S. National Cancer Institute. The ritterazines and cephalostatins share many common structural features in which two highly oxygenated steroidal units with side chains forming either 5/5 or 5/6 spiroketals are fused via a pyrazine core. Professor P. L. Fuchs and colleagues reported the total syntheses of 1, cephalostatins 7 ( 7), and 12 ( 12), ritterazines K ( 30) and M ( 32), and cytotoxic analogues. The synthesis of 1, described in 1998, required 65 synthetic operations to complete.
Moser
Bryan R
BR
United States Department of Agriculture, National Center for Agricultural Utilization Research, Peoria, Illinois 61604, USA. Bryan.Moser@ars.usda.gov
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002816:Chordata, Nonvertebrate / Q000737:chemistry; D015394:Molecular Structure; D010619:Phenazines / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014561:Urochordata / Q000737:chemistry
D000970:Antineoplastic Agents; D001688:Biological Products; D010619:Phenazines; D013141:Spiro Compounds; D013256:Steroids; C529027:ritterazine A; C473897:ritterazine B; C454806:cephalostatin I