Structure elucidation of liposidomycins, a class of complex lipid nucleoside antibiotics

The Journal of Organic Chemistry
1992.0

Abstract

Lipidomycins A, B, and C are novel lipid nucleoside antibiotics produced by Streptomyces pkeosporeus, which strongly inhibit bacterial peptidoglycan synthesis. Detailed structure aualysis of lipidomycins A, B, and C and of their chemical degradation products by NMR and maee spectrometry shows that they each passege 5'-substituted uridine, 5-amino-&deoxyribo~e-2-sulfate, and perhydro-l,4diazepine 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)ttradecanoic acid, respectively, and lipidomycin B contains 3-(3'-methylglutaryl)-1%methyltrideamoic acid Using lipoeidomycin B aa a central structural model, a detailed fragmentation map from collision-indud dissociation was produced using tandem mass spectrometry. The resulting data were used for partial characterization of structural subunite and in establishing sites and order of interconnectivity of subunits in the intact molecule. Structure of the fatty acid component of lipidomycin A as 3-hydroxy-7,lO-hexadecadienoic acid, a previously unknown natural product, waa establiahed principally by chargeremote fragmentation using a technique involving micrde lipid hydrolysis and lithiation using LiOH. These methods should have general utility in structural studies of complex natural product familiee whose members share common structural subunite.

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