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

Dissolution of brefeldin-A in CDCl3 afforded two species in We ratio 13:3. Vicinal proton-proton coupling constants and NOE intensity enhancement meas urements showed that the 13-membered ring conformation found by x-ray cryst allography 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-member ed ring conformation exists in a small amount. While some degree of conform ational flexibility for the major species cyclopentyl ring cannot be ruled out, the O-13 hydroxyl group is clearly axially disposed in the solution st ate as it is in the crystal. Comparison of the solution-state C-13 NMR chem ical shifts of the major species with those values measured by solid-state cross-polarization magic angle spinning show fairly good agreement with dif ferences usually of 1 ppm, or less, with the exception of C-2,8,6,11,15 sig nals where differences were ca 2-3 ppm. Copyright (C) 2000 John Wiley & Son s, Ltd.