HAPALOSIN, A CYANOBACTERIAL CYCLIC DEPSIPEPTIDE WITH MULTIDRUG-RESISTANCE REVERSING ACTIVITY

Hapalosin (2), a novel cyclic depsipeptide from the blue-green alga (cyanobacterium) Hapalosiphon welwitschii W. and G. S. West (Stigonemataceae), shows MDR-reversing activity. Its structure has been determined to be (3S,4R,8R,9S, 12S)-9-benzyl-4-heptyl-8-hydroxy-12-isopropyl-3,10-dimethyl-1,5-dioxa-10-azacyclododecane-2,6,11-trione by a combination of spectroscopic and chemical methods. The carbon skeleton of 2 was determined by two-dimensional H-1-H-1 and H-1-C-13 NMR correlation experiments and confirmed by mass spectral analysis. The relative and absolute stereochemistry was determined by coupling constant data and Mosher analysis of 2 and three degradation products obtained from acid hydrolysis of 2.