Towards the Enantioselective Total Synthesis of Viburspiran

Abstract

Viburspiran belongs to the class of maleidride natural products and it exhibits interesting biological properties such as antifungal activity. While no total synthesis of viburspiran has been reported, studies in our group are ongoing using a photochemical approach. This report focuses on asymmetric strategies applied to the current route to enable an enantioselective synthesis of
viburspiran.

The first approach made use of chiral auxiliaries, but this proved unsatisfactory. To overcome this problem, an organocatalytic reaction was investigated, giving better results. Having obtained aldehyde 10 via an asymmetric conjugate addition using the chiral proline-derived catalyst (S)-9, Pinnick oxidation followed by Fisher esterification, intramolecular Claisen condensation and ⁱPrOH protection finally afforded the six-membered enol ether 11 with an enantiomeric excess of
approximately 89%, successfully completing an asymmetric route to this key intermediate.

Date of Award	5 Dec 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	Paul J Gates (Supervisor) & Chris L Willis (Supervisor)