Periwinkles As Drug Factories

Chemists have prodded seedlings of the medicinal periwinkle plant to make a variety of nonnatural terpene indole alkaloids in a process that could help produce hard-to-synthesize drugs (J. Am. Chem. Soc. 2006, 128, 14276). The periwinkle normally produces a treasure trove of natural products, including the anticancer agent vinblastine (shown, Me = methyl, Ac = acetyl), which is assembled in mature plants from two tryptamine-based precursors (tryptamine-derived portion is red). Semisynthetic derivatives of vinblastine continue to show promise in clinical trials, notes Sarah E. O'Connor of MIT. In hopes of easing access to these and other nonnatural vinblastine analogs, O'Connor and Elizabeth McCoy fed periwinkle seedlings various tryptamine derivatives. The seedlings make a variety of complex terpene indole alkaloids from the tryptamine derivatives, including analogs of the precursors from which vinblastine is assembled. Manipulating natural biosynthetic pathways in this way is common in bacteria but it's largely untackled in plants, the researchers note.