Total structures of cryptophycins, potent antitumor depsipeptides from the blue-green alga Nostoc sp. strain GSV 224

Article abstract of DOI:10.1021/ja00090a020

Cryptophycin (A, 1), the major cytotoxin in the blue-green alga (cyanobacterium) Nostoc sp. GSV 224, shows excellent activity against solid tumors implanted in mice. This cyclic depsipeptide had previously been isolated from Nostoc sp. ATCC 53789 as an antifungal agent and its gross structure determined by researchers at Merck. The relative and absolute stereochemistry of this potentially important drug has now been established using a combination of chemical and spectral techniques. Six minor cryptophycins (B-G, 2-7) have also been isolated from GSV 224 and their total structures and cytotoxicities determined. Two types of cryptophycins are present in this alga, the major series possessing a monochlorinated L-O-methyltyrosine unit and the minor series possessing a nonchlorinated D-O-methyltyrosine unit. Structure-activity relationship (SAR) studies of the cryptophycins and several derivatives and degradation products (8-14) are described. Also presented are preliminary in vivo results for cryptophycin A against six solid tumors.