Caballero Esmeralda, Avendaño Carmen, Menéndez J Carlos
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
J Org Chem. 2003 Sep 5;68(18):6944-51. doi: 10.1021/jo034703l.
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.
曲普他汀B由易于获得的二肽酸酐环-（L-色氨酸-L-脯氨酸）以32%的总产率合成。其串联的C-3异戊烯基化/环化反应生成了在吲哚C-3位带有异戊烯基的相应五环吡咯并吲哚体系。然后将这些化合物进行新形成环的酸催化开环反应，同时异戊烯基迁移至吲哚C-2位。还使用类似的步骤制备了曲普他汀B的丙氨酸类似物。该策略的成功实施进一步证明了存在一条沿着类似路线合成曲普他汀的生物合成途径。
