Total synthesis of (±)-pisiferic acid

Abstract

A total synthesis of (±)-pisiferic acid (1) has been achieved by utilising the keto ether (22) which, in turn, was prepared from the alcohol (14). Subjection of the keto ether (22) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone, and intramolecular aldol condensation) provided the tricyclic ether (27) whose conversion into the methoxyabietatriene (32) was accomplished in four steps (ethoxycarbonylation, Grignard reaction with methyl-lithium, acid-catalysed dehydration, and methoxylation). Reaction of the methoxyabietatriene (32) with zinc, zinc iodide, and acetic acid produced (±)-pisiferol (2) which was finally converted into (±)-pisiferic acid (1). The ketone (34) was converted into the abietatriene (41) following exactly the same procedure adopted for the transformation of the keto ether (22) into the abietatriene (32). Hydroboration-oxidation of (41) followed by oxidation with Jones reagent and reduction with lithium aluminium hydride followed by transannular oxidation gave the abietatriene (36).