High-Field FT NMR Application of Mosher's Method. the Absolute Configurations of Marine Terpenoids

Article abstract of DOI:10.1021/ja00011a006

Mosher's (¹H) method to elucidate the absolute configuration of secondary alcohols was reexamined by use of high-Held FT NMR spectroscopy, which enables assignment of most of the protons of complex molecules. There is a systematic arrangement of Δδ (δ_s - δ_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 Δδ 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 Δδ 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.