High-Field FT NMR Application of Mosher’s Method. The Absolute Configurations of Marine Terpenoids

Mosher’s (¹H) method to elucidate the absolute configuration of secondary alcohols was reexamined by use of high-field FT NMR spectroscopy, which enables assignment of most of the protons of complex molecules. There is a systematic arrangement of d (d_s - &_R) values obtained for the (R)- and (S)-MTPA esters of (−)-menthol, (−)-borneol, cholesterol, and ergosterol, the absolute configurations of which are known. Analysis of the?d values of these compounds led to a rule that could predict the absolute configurations of natural products. When this rule was applied to some marine terpenoids including cembranolides and xenicanes, their absolute configurations were assigned and a part of the results were confirmed by X-ray structural analyses. In the case of sipholenol A, which has a sterically hindered OH group, this rule is inapplicable. But the problem is overcome by inverting the OH group to a less sterically hindered position; the resulting epimer gives systematically arranged?d values, which enabled the elucidation of the absolute configuration. Comparison of the present method with Mosher’s ¹⁹F method indicates that the latter one using ¹⁹F NMR lacks in reliability.