NMR structure determination of brefeldin-A, a 13-membered ring fungal metabolite

Abstract

Dissolution of brefeldin-A in CDCl3 afforded two species in the ratio 13 : 1. Vicinal proton–proton coupling constants and NOE intensity enhancement measurements showed that the 13-membered ring conformation found by x-ray crystallography in the solid state appears to be preferred also in the solution-state major species. The observance of signals from a solution-state minor species (e.g. for the C-15 methyl) shows that at least one other 13-membered ring conformation exists in a small amount. While some degree of conformational flexibility for the major species cyclopentyl ring cannot be ruled out, the O-13 hydroxyl group is clearly axially disposed in the solution state as it is in the crystal. Comparison of the solution-state 13C NMR chemical shifts of the major species with those values measured by solid-state cross-polarization magic angle spinning show fairly good agreement with differences usually of 1 ppm, or less, with the exception of C-2,8,6,11,15 signals where differences were ca 2–3 ppm. Copyright © 2000 John Wiley & Sons, Ltd.