An efficient stereochemical elucidation of the aromatic polyketide NFAT-133 using the novel NOE quantification combined with nJ H-H and nJ C-H coupling constants.

Abstract

NFAT-133, which was isolated from Streptomyces sp., is an immunosuppressive and antidiabetic aromatic polyketide containing three contiguous stereocenters. Although its absolute configuration was first proposed mainly based on NMR data, the later study employing the total synthesis of the proposed structure and its epimer resulted in the stereochemical revision of NFAT-133. The difficulty of determining relative configuration in polyketides arises from spin systems consisting of a methine group directly bonded to a methyl group (e.g. -CH(OH)-CH(CH₃)-CH(OH)-). In this case, the stereochemical analysis of the aforementioned chain structure is generally hard due to the limited information of ⁿJ_C-H and ⁿJ_H-H. In an aim of developing a reliable analytical method based on NMR spectroscopy, we applied a novel NOE quantification in a 1D double pulsed field gradient spin echo (DPFGSE)-NOESY spectra. The combinational analysis of the proposed NOE quantification with ⁿJ_C-H and ⁿJ_H-H provided an accurate determination of the relative configurations.