By addressing the relative stereochemistry of the four
acyclic portions via organic synthesis, the complete
relative stereochemistry of maitotoxin (MTX) has been established as
1B. The relative stereochemistry of the
C.1−C.15 portion was elucidated via a two-phase approach: (1) the
synthesis of the eight diastereomers possible for
model C, representing the C.1−C.11 portion, and the eight
diastereomers possible for model D, representing
the
C.11−C.15 portion, and the comparison of their proton and carbon NMR
characteristics with those of MTX, concluding
that 9 and 35 represent the relative
stereochemistry of the corresponding portions of MTX; (2) the synthesis
of the
two remote diastereomers 51 and 52, and
comparison of their proton and carbon NMR characteristics with those
of
MTX, concluding that 51 represents the relative
stereochemistry of the C.1−C.15 portion of MTX. The
relative
stereochemistry of the C.35−C.39, C.63−C.68, and C.134−C.142
acyclic portions was established via (1) the synthesis
of the 8, 8, and 16 diastereomers possible for models E,
F, and G, respectively, and (2) the comparison of
their
proton and carbon NMR characteristics with those of MTX, concluding
that 81, 117, and 187, respectively,
represent
the relative stereochemistry of the corresponding portions of MTX.
Some biogenetic considerations have been given
to speculate on the absolute configuration of MTX. The vicinal
proton coupling constants observed for models
51,
81, 117, and 187 were used to
elucidate their preferred solution conformation. Assembling the
preferred solution
conformations found for the four acyclic portions allows one to suggest
that the approximate global conformation of
MTX is represented by the shape of a hook, with the C.35−C.39 portion
being its curvature. MTX appears to be
conformationally relatively rigid, except for conformational
flexibility around the C.7−C.9 and C.12−C.14 portions.
On the basis of the experimental results gained in the current
work, coupled with those in the AAL-toxin/fumonisin
area, it has been pointed out that the structural properties of
51, 81, 117, 187 and their
diastereomers are inherent to
the specific stereochemical arrangement of the small substituents on
the carbon backbone and are independent from
the rest of the molecule. Thus, it has been suggested that each of
these diastereomers has the capacity to install a
unique structural characteristic through a specific stereochemical
arrangement of substituents on the carbon backbone,
and that fatty acids and related classes of compounds may be able to
carry specific information and serve as functional
materials in addition to structural materials.
