Structure Elucidation of Liposidomycins, a Class of Complex Lipid Nucleoside Antibiotics

Abstract

Liposidomycins A, B, and C are novel lipid nucleoside antibiotics produced by Streptomyces griseosporeus, which strongly inhibit bacterial peptidoglycan synthesis. Detailed structure analysis of liposidomycins A, B, and C and of their chemical degradation products by NMR and mass spectrometry shows that they each possess 5′-substituted uridine, 5-amino-5-deoxyribose-2-sulfate, and perhydro-1,4-diazepine moieties, but differ in the structures of the lipid side chains. Liposidomycins A and C contain 3-(3′-methylglutaryl)-7,10-hexadecadienoic acid and 3-(3′-methylglutaryl)tetradecanoic acid, respectively, and liposidomycin B contains 3-(3′-methylglutaryl)-12-methyltridecanoic acid. Using liposidomycin Basa central structural model, a detailed fragmentation map from collision-induced dissociation was produced using tandem mass spectrometry. The resulting data were used for partial characterization of structural subunits and in establishing sites and order of interconnectivity of subunits in the intact molecule. Structure of the fatty acid component of liposidomycin A as 3-hydroxy-7,10-hexadecadienoic acid, a previously unknown natural product, was established principally by charge-remote fragmentation using a technique involving microscale lipid hydrolysis and lithiation using LiOH. These methods should have general utility in structural studies of complex natural product families whose members share common structural subunits. © 1992, American Chemical Society. All rights reserved.