POTENT CYTOTOXIC METABOLITES FROM A LEPTOSPHAERIA SPECIES - STRUCTURE DETERMINATION AND CONFORMATIONAL-ANALYSIS

New cytotoxic epipolysulfanyldioxopiperazine dimers, leptosins K (4), K-1 (5) and K-2 (6), have been isolated from a strain of Leptosphaeria sp. originally isolated from the marine alga Sargassum tortile. Their stereostructures, with a different configuration from that of leptosins A-C, have been elucidated by spectral and X-ray analyses and some chemical transformations. X-Ray and NMR and NOE spectral analyses of 4 revealed that it exists in a mixture of four conformers, of which two each closely resemble, in a single crystal, and in a single conformer in solution. NOE experiments of 5 and 6 demonstrated that they exist in a mixture of two conformers slowly exchanging in CDCl3.