Two-Dimensional NMR Analysis of Acetonide Derivatives in the Stereochemical Assignment of Polyol Chains: The Absolute Configurations of Dermostatins A and B

Abstract

We report a new, integrated strategy for assigning the configuration of 1,3-skipped polyol chains and illustrate the approach with the configurational assignments of both dermostatins A and B. The method is designed around the (13)C acetonide analysis, which allows one to reliably determine the relative stereochemistry of an isolated 1,3-diol and is extended using DQF-COSY, HMQC, and ROESY experiments that allow each acetonide of a polyacetonide derivative to be unambiguously assigned as either syn or anti. Using this strategy, the relative configuration of the dermostatin A C13-C32 polyol chain was determined using just two polyacetonide derivatives. The absolute configuration of dermostatin A is 15S,16S,17R,19R,21R,23S,25S,27R,29R,31R,34S,35S, and the configuration of dermostatin B is 15S,16S,17R,19R,21R,23S,25S,27R,29R,31R,34S,35S,36S. The 2D (13)C acetonide analysis is a very powerful new tool for the stereochemical assignment of alternating polyol chains.