Antineoplastic agents. 561. Total synthesis of respirantin.

Abstract

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.

• Authors: George R Pettit, Thomas H Smith, Song Feng, John C Knight, Rui Tan, Robin K Pettit, Peter A Hinrichs
• Journal: Journal of natural products (J Nat Prod) Vol. 70 Issue 7 Pg. 1073-83 (Jul 2007) ISSN: 0163-3864 [Print] United States
• PMID: 17608531 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Depsipeptides
• respirantin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cryptococcus neoformans (drug effects)
• Depsipeptides (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Mice
• Microbial Sensitivity Tests
• Molecular Structure
• Structure-Activity Relationship