Edwankar CR, Edwankar RV, Deschamps JR, Cook JM * University of Wisconsin-Milwaukee
and Naval Research Laboratory, Washington, D. C., USA
Nature-Inspired Stereospecific Total Synthesis of
P-(+)-Dispegatrine and Four Other Monomeric
Sarpagine Indole Alkaloids.
Angew. Chem. Int. Ed. 2012;
51: 11762-11765
Key words
dispegatrine - sarpagine alkaloids - carbonyl vinylation - thallium - oxidative biaryl
coupling - dimerization
Significance
Reported in this work is the first total synthesis of P‑(+)-dispegatrine, a complex dimeric sarpagine indole alkaloid, which has been shown to exhibit anti-hypertensive activity due to
its affinity to both the α1 and α2 adrenoreceptors. In addition to an efficient asymmetric
route, the synthetic efforts toward this natural product have also led to the determination
of the absolute configuration around the biaryl axis, which had previously been left
unassigned by the isolation group.
Comment
The most notable feature in the synthetic route presented above is a thallium-mediated
oxidative dimerization of (+)-lochnerine (E) which regioselectively delivers the desired dimer F. Thereby, the rigid chiral framework of the monomer dictates atroposelection during
the dimerization reaction, leading exclusively to the naturally occuring atropodiastereomer
(P-isomer). This and similar results from an earlier semi-synthetic study led to the
proposal that the biaryl coupling might closely parallel the biosynthetic route.
