Antineoplastic agents. 561. Total synthesis of respirantin.
Total synthesis of the 18-membered ring cyclodepsipeptide believed to be respirantin (1b) has been achieved. The key step in the synthesis is an intramolecular transesterification of the beta-ketoester alcohol 6 to afford the protected macrocycle 5. The synthetic product was shown to be identical to a natural product presumed to be respirantin (1b), and the absolute stereochemistry of six of the seven asymmetric centers of cyclodepsipeptide 1b was unequivocally established. Respirantin (1b) was found to be a remarkable inhibitor of cancer cell growth and related to the antimycin family of antibiotics.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Smith
Thomas H
TH
Feng
Song
S
Knight
John C
JC
Tan
Rui
R
Pettit
Robin K
RK
Hinrichs
Peter A
PA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000187:drug effects; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047630:Depsipeptides; C081425:respirantin