Structure Revision of
Plakotenin Based on Computational
Investigation of Transition States and Spectroscopic Properties
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Abstract
We show that the previously [<i>Tetrahedron Lett.</i> <b>1992</b>, <i>33</i>, 2579] proposed structure
of natural plakotenin must be revised. Recently, the total synthesis
of plakotenin was achieved via an intramolecular Diels–Alder
reaction from a (<i>E,E,Z,E</i>)-tetraene as linear precursor.
Using density functional theory, the computation of the four possible
transition states for this reaction shows that the previously proposed
structure could only have been formed via an energetically high-lying
transition state, which is very unlikely. Instead, we suggest that
the structure of plakotenin corresponds to the product formed via
the lowest transition state. A comparison of experimental and theoretical
optical rotation, circular dichroism, and two-dimensional nuclear
Overhauser enhancement spectra conclusively proves that the structure
of plakotenin is the one that is suggested by the transition state
computations. Moreover, the simulation of the nuclear Overhauser enhancement
spectra suggests that it is most likely that the misassignment of
the <sup>1</sup>H chemical shifts of two methyl groups has led to
the wrong structure prediction in the 1992 work. The previously proposed
structure of <i>iso</i>-plakotenin remains unaffected by
our structure revision, but the structures of <i>homo</i>- and <i>nor</i>-plakotenin must also be revised. The present
work shows how the total synthesis of a natural product, together
with the theoretical determination of the barrier heights of the reactions
involved, can be of great help to assign its structure. It appears
that intramolecular Diels–Alder reactions can be modeled accurately
by today’s first-principles methods of quantum chemistry