Regioselective Pd-catalyzed alkylations of 3,5-dibromo-2-pyrone and application toward total synthesis of (±)-phomactin A and its analogsRegioselective Pd-catalyzed alkylations of 3,5-dibromo-2-pyrone and application toward total synthesis of (±)-phomactin A and its analogsRegioselective Pd-catalyzed alkylations of 3,5-dibromo-2-pyrone and application toward total synthesis of (±)-phomactin A and its analogs

Abstract

Phomactin A is an oxygenated diterpene isolated by Sugano and coworkers in early 1990s from Phoma sp., featuring tricyclic furanochroman skeleton integrated with 12-membered macrocycle. In addition to the unique structural profile, phomactin A has a wide spectrum of intriguing physiological functions including PAF (platelet activating factor) antagonistic activity, triggering intensive synthetic studies over the past few years. Because of the high structural complexity, however, only two total syntheses were reported; racemic synthesis by Pattenden group and asymmetric synthesis by Halcomb group, both of which involve more than 50 steps. Searching for a more flexible and efficient synthetic approach, we designed a new approach starting from 3,5-dibromo-2-pyrone toward phomactin A involving regioselective Pd-catalyzed alkylation, Diels-Alder cycloaddition and Suzuki B-alkylation reaction.