Brief Total Synthesis of the Cell Cycle Inhibitor Tryprostatin B and Related Preparation of Its Alanine Analogue

Abstract

Tryprostatin B was synthesized in 32% overall yield from the readily available dipeptide anhydride cyclo-(l-Trp-l-Pro). Its tandem C-3 prenylation/cyclization gave the corresponding pentacyclic pyrroloindole systems bearing a prenyl group at the indole C-3 position. These compounds were then submitted to acid-catalyzed opening of the newly formed ring, with concomitant migration of the prenyl group to the indole C-2 position. The alanine analogue of tryprostatin B was also prepared using a similar sequence. The successful implementation of this strategy strengthens the case for a biosynthetic route for the tryprostatins along similar lines.