NOVEL LONG-RANGE ISOTOPE EFFECTS IN A MACROLIDE ANTIBIOTIC - BAFILOMYCIN-A1

The 1H and 13C NMR spectra of bafilomycin A 1 (1), 21-O-trimethylsilylbafilomycin A1 (2) and 7-O-acetyl-21-O-t-butyldimethylsilylbafilomycin A1 (3) have been unambiguously solved in a variety of solvents by 1D and 2D NMR techniques. Partial deuteriation of the hydroxy groups of (1), (2), and (3) led to the observation of many novel and long-range isotope effects in the 1H and 13C spectra of (1), (2), and (3). These experiments also confirmed the existence in solution of the hydrogen-bonding network involving 19-OH, 17-OH, and C(1)=O for (1), (2), and (3), as was found in the crystalline state for (1). The possible mechanisms of the isotope effects are discussed.