SYNTHESIS OF CYCLODEPSIPEPTIDE COMPOUNDS HAVING ANTINEOPLASTIC AND/OR ANTIMICROBIAL ACTIVITY

摘要

The present invention is directed to effective methods of synthesizing cyclodepsipeptide compounds having antineoplastic and/or antimicrobial activity. Total syntheses of the eighteen-membered ring cyclodepsipeptides kitastatin (1a) and respirantin (1b) are taught. One important step in the synthesis is an intramolecular transesterification of the ?-ketoester alcohol 6 to afford the protected macrocycle 5. The synthetic products were shown to be identical to the natural products and the absolute stereochemistry of 6 of the 7 asymmetric centers of cyclodepsipeptide 1b was unequivocally established. Kitastatin (1a) and respirantin (1b) were found to be remarkable inhibitors of cancer cell growth and are related to the antimycin family of antibiotics.