Isobenzofurans as synthetic intermediates: Synthesis and biological activity of 8-epi-(–)-ajudazol B

Abstract

Ajudazol B is a polyketide secondary metabolite, isolated from the myxobacterium Chondromyces crocatus, that exhibits potent biological activity. Herein, we report a convergent total synthesis of 8-epi-(–)-ajudazol B. The key step is a regio-selective alkylation and oxidative rearrangement of a reactive isobenzofuran intermediate that generates the isochromanone core. This approach provides a fast and efficient method to synthesise analogues of ajudazol B from simple aldehydes, allowing assessment of structure-activity relationships. The antifungal activity of 8-epi-(–)-ajudazol B as well as that of related analogues has been assessed using Botrytis cinerea. The results indicate that the isochromanone unit is key for antifungal activity.