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
, 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 possible rotamers.