A Suzuki–Miyaura Coupling of ortho-Hydroxyaryl Bromide with Isopropenylboronic Pinacol Ester: Synthesis of the Potassium-Channel Opener (+)-Callitrisic Acid

Abstract

A Suzuki–Miyaura coupling reaction of ortho-hydroxyaromatic bromide 8 with isopropenylboronic acid pinacol ester has been investigated. It was found that the catalyst of Pd2(dba)3/PCy3 in dioxan-water gave good yield by suppressing the formation of isomeric side product 14. (+)-Callitrisic acid was synthesized from (+)-podocarpic acid using this condition with an overall yield of 54 % in about five steps. (+)-Callitrisic acid was found to be almost three times more potent than dehydroabietic acid to open a voltage-gated potassium channel.