A NMR method for relative stereochemical assignments of the tricyclic core of cephalosporolides, penisporolides and related synthetic analogues

Abstract

The misassignments of the relative configuration of natural products such as cephalosporolides H and I and penisporolide B were frequently detected by synthetic studies (total synthesis) with considerable effort and cost. Reported herein is the development of a NMR analysis method that can be applied to reliably discriminate the four possible diastereomers of the tricyclic core of cephalosporolides and penisporolides using only proton and/or carbon NMR data without relying on sophisticated 2D NMR spectral analysis. The effectiveness of this NMR method was examined with 28 synthetic compounds, leading to detection and/or correction of 11 misassignments.