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 ap proach: (1) the synthesis of two diastereomeric models Me-A and Me-B a nd (2) the comparison of the NMR spectroscopic data for each model wit h those of maitotoxin. Furthermore, the fact that the NMR characterist ics observed for Me-A were remarkably close to those reported for mait otoxin makes a strong case for the accurate extrapolation of the confo rmational properties of maitotoxin from those of the model Me-A. Using H-1-H-1 NOESY experiments and MM3 calculations, the solution conforma tions 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 a dopt the conformations Me-Aa and Me-Ba, respectively, due to intramole cular hydrogen bond stabilization. On the other hand, in a protic solv ent such as a 1:1 mixture of methanol and pyridine both Me-A and Me-B exist as mixtures of all of their possible rotamers.