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. & G. S. West (Stigonemataceae), shows MDR-reversing activity. Its structure has been determined to be (3S,4S,8S,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 ¹H— and ¹H—¹³C 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.