THE STEREOCHEMICAL ASSIGNMENT AND CONFORMATIONAL ANALYSIS OF THE V/W-RING JUNCTURE OF MAITOTOXIN

The unambiguous stereochemical assignment of the V/W-ring juncture of maitotoxin, as shown in Figure 1, was accomplished using a two-step approach:  (1) the synthesis of two diastereomeric models Me-A and Me-B and (2) the comparison of the NMR spectroscopic data for each model with those of maitotoxin. Furthermore, the fact that the NMR characteristics observed for Me-A were remarkably close to those reported for maitotoxin makes a strong case for the accurate extrapolation of the conformational properties of maitotoxin from those of the model Me-A. Using 1H−1H NOESY experiments and MM3 calculations, the solution conformations of Me-A and Me-B were studied in aprotic and protic solvents. In aprotic solvents such as benzene, both Me-A and Me-B preferentially adopt the conformations Me-Aa and Me-Ba, respectively, due to intramolecular hydrogen bond stabilization. On the other hand, in a protic solvent such as a 1:1 mixture of methanol and pyridine both Me-A and Me-B exist as mixtures of all of their possibl...