Archazolid-7-O-β-D-glucopyranoside -: Isolation, structural elucidation and solution conformation of a novel V-ATPase inhibitor from the myxobacterium Cystobacter violaceus

The novel polyketide macrolide archazolid-7-O-beta-D-gluco-pyranoside (3) has been isolated from the myxobacterium Cystobacter violaceus and the structure of this first archazolidglycoside has been determined by spectroscopic and degradative methods. A synthesis of simplified 7-O analogues, based on regioselective derivatisation of archazolid A, was elaborated. These structurally novel archazolids of natural and synthetic origin were evaluated in detail for V-ATPase inhibition and their biological activities are discussed in terms of their solution conformations, as determined by high-field NMR studies, including J-based conformation analysis and constrained molecular dynamics simulations. (C) Wiley-VCH Verlag GmbH & Co.