posted on 2015-09-02, 00:00authored byReed T. Larson, Ryan P. Pemberton, Jenna
M. Franke, Dean J. Tantillo, Regan J. Thomson
The
enantioselective total syntheses of himandravine and GB17 were
completed through a common biomimetic strategy involving Diels–Alder
reactions of unusual double diene containing linear precursors. The
double diene precursors, containing or lacking a C12 substituent as
required to produce GB17 or himandravine, respectively, were found
to undergo Diels–Alder reactions to afford mixtures of regioisomeric
cycloadducts that map onto the alternative carbocyclic frameworks
of both himandravine and GB17. Computational investigations revealed
that these Diels–Alder reactions proceed via transition state
structures of similar energy that have a high degree of bispericyclic
character and that the low levels of regioselectivity observed in
the reactions are a consequence of competing orbital interaction and
distortion energies. The combined experimental and computational results
provide valuable insights into the biosynthesis of the Galbulimima alkaloids.