Structural Revision of Uprolide G Acetate: Effective Interplay between NMR Data Analysis and Chemical Synthesis

Abstract

The molecular structure of the cytotoxic cembranolide uprolide G acetate (UGA) was proposed in 1995 and subsequently revised in 2000 on the basis that NMR data for UGA were very similar to those of a synthetic analogue that was unambiguously confirmed by X-ray diffraction analysis. Our synthetic studies of UGA suggested that the revised structure for UGA was still incorrect. Therefore, two new possible structures for UGA were proposed based on comprehensive NMR data analysis. The proposed structures were synthesized in 33 steps by exploitation of Achmatowicz rearrangement, ring-closing metathesis, and Sharpless asymmetric dihydroxylation as the key steps. Their analysis led to the identification of the correct structure for UGA. The success of structural revision of UGA illustrated well the importance of the interplay between NMR data analysis and chemical synthesis.

Key words

structure elucidation - cembranolide - uprolide - total synthesis - natural products

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