Stereoselective total syntheses of (±)-isoagatholactone and (±)-12α-hydroxyspongia-13(16),14-diene, two marine sponge metabolites

Abstract

The highly efficient, stereoselective syntheses of (±)-isoagatholactone (1a) and (±)-12α-hydroxyspongia-13(16),14-diene (3e), a fundamental skeleton of spongiadiol (3a) and its related furanoid diterpenes, are described. (±)-Labda-8(20),13-dien-15-oic acid (6), chosen as the starting material, was cyclised to the known tricyclic compound (2b), which after methylation was subjected to photo-oxygenation, yielding the allylic alcohol (7a). Refluxing of the alcohol (7a) with 3.5% sulphuric acid in dioxan afforded the lactone (1b), which after reduction with lithium aluminium hydride led to the diol (2g). Subsequent oxidation of this diol with Collins reagent provided the desired compound (1a). The key precursor for the synthesis of compound (3e) was the allylic alcohol (7a) obtained above. On epoxidation the alcohol (7a) gave the epoxide (13), which by the action with lithium di-isopropylamide led to the α,β-unsaturated γ-lactone (14). Subsequent reduction of this lactone with di-isobutylaluminium hydride afforded the furan (3e).