Stereochemical Determination of Acyclic Structures Based on Carbon−Proton Spin-Coupling Constants. A Method of Configuration Analysis for Natural Products

Abstract

A method for elucidating the relative configuration of acyclic organic compounds was developed on the basis of carbon−proton spin-coupling constants (^2,3J_C,H) and interproton spin-coupling constants (³J_H,H). This method is based on the theory that, in acyclic systems, the conformation of adjacent asymmetric centers is represented by staggered rotamers, and their relative stereochemistry can be determined using ^2,3J_C,H and ³J_H,H, because the combined use of these J values enables the identification of the predominant staggered rotamer(s) out of the six possible derived from threo and erythro configurations. Detailed conformational analysis for model compounds 1−4 revealed that this method is useful in most cases for assignment of the configuration of acyclic structures occurring in natural products, in which stereogenic methine carbons are often substituted with a methyl or a hydroxy (alkoxy) group. This J-based configuration analysis was applied to the stereochemical elucidation of carboxylic acid 5 derived from zooxanthellatoxin and proven to be a practical method even for natural products with complicated structures.