Ishikawa H,
Elliott GI,
Velcicky J,
Choi Y,
Boger DL *.
The Scripps Research Institute, La Jolla, USA
Total Synthesis of (–)- and
ent-(+)-Vindoline and Related Alkaloids.
J. Am. Chem. Soc. 2006;
128: 10596-10612
DOI:
10.1021/ja061256t
Keywords
(–)-vindoline - indole alkaloid natural products - hetero-Diels–Alder reaction - nitrogen
extrusion - oxonium ylide cycloaddition
Significance
In 2006, Boger and co-workers reported the total synthesis of (–)-vindoline, an indole
alkaloid derived from the plant Cantharanthus roseus. This natural product has garnered considerable interest due to its complex polycyclic
scaffold. Additionally, and importantly, (–)-vindoline is a structural constituent
of the highly complex microtubule formation inhibitors vinblastine and vincristine.
Comment
The synthesis hinges on a cascade of reactions initiated upon heating of key oxadiazole
E: an intramolecular hetero-Diels–Alder reaction is followed by cycloreversion, yielding
intermediate oxonium ylide H. This five-membered ylide further reacts with the pendent indole and affords oxa-bicycle
I. Final functional group interconversions complete the synthesis of (–)-vindoline.
