Total Synthesis of (–)-Vindoline

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.

Publication History

Article published online:
26 November 2025