Synthesis of the Briarane northern hemisphere

Abstract

A large group of marine natural products isolated over the last few years is the briaranes. Over 300 have been isolated, all based on a ring system containing a six membered ring, a ten membered ring and a butenolide, or its oxidised form. Biological studies on the briaranes have revealed a range of activities. Our approach to the synthesis of the briaranes uses a modular approach that should be sufficiently flexible to allow for the synthesis of a variety of these natural products. The preparation of the six-membered ring containing with upper chain as a potential building block was achieved. The Robinson annulation reaction employing P-ketoesters under very mild conditions could not be used to prepare the desired cyclohexenone ester. However, the six-membered ring was obtained by an unusual Diels-Alder reaction of a sulfonyl diene. The Diels-Alder adduct was further manipulated by a series of reactions including oxidative desulfonylation, Eschenmoser-Claisen rearrangement, halo-lactonisation, and enolate hydroxylation using MoOPD.