Structure of YM-254890, a Novel Gq/11 Inhibitor from Chromobacterium sp. QS3666

The isolation and structure elucidation of YM-254890, a novel G_q/11 inhibitor from Chromobacterium sp. QS3666, is described. The gross structure was determined by one- and two-dimensional NMR studies and mass spectrometry. YM-254890 is a cyclic depsipeptide containing uncommon amino acids; β-hydroxyleucine (two residues), N,O-dimethylthreonine and N-methyldehydroalanine. YM-254890 exists as a mixture of two conformers in a variety of NMR solvents, and the distinction between major and minor conformers appears to lie in the geometry of the amide bond between 3-phenyllactic acid and N-methyldehydroalanine. The absolute stereochemistery was elucidated by Marfey's analysis and chiral HPLC analysis of the acid hydrolysate of YM-254890.