The conformational analysis of bafilomycin A1

Abstract

The ¹H and ¹³C n.m.r. spectra of bafilomycin A₁, (1a), have been unambiguously solved by two-dimensional (2D) n.m.r. methods. Comparison of this spectral data with that reported for two other hygrolide antibiotics L-681, 110A₁(1b) and L-155, 175 (1c), shows that the (Z)-C(4)–C(5) double bonds assigned to the latter two compounds are in fact E. The solution-state conformations of bafilomycin A₁ have been determined by the use of proton–proton coupling constants, ₁H nuclear Overhauser enhancements (n.O.e.s), and ¹³C spin–lattice relaxation times (T₁s). The solution-state conformations have been compared with the known crystalline-state conformation of bafilomycin A₁(with the aid of molecular modelling techniques) and are found to be very similar. In particular, it can be concluded that the hydrogen-bonding network involving 19-OH, 17-OH, and C(1)O is intact in CDCl₃ solution.