The total synthesis of natural products using cyclisation strategies

This thesis is concerned with the total syntheses of natural products and the development of a novel diastereoselective radical cyclisation reaction. Total syntheses of marine sesquiterpenes aplysin and debromoaplysin are described. The key step involves a diastereoselective, sulfur mediated radical cyclisation that simultaneously creates the sterically demanding aplysin skeleton and establishes the relative configuration of the three contiguous stereogenic centres.Total syntheses of aplysin, debromoaplysin, aplysinol, debromoaplysinol, isoaplysin, isolaurinterol and debromoisolaurinterol are described. Key features are a diastereoselective radical to polar crossover sequence mediated by tin, and a series of biomimetic cyclisation and oxidation reactions.The first reported total synthesis of the linear triquinane 1-desoxyhypnophilin is described, using a ring closing metathesis, allylic oxidation and regioselective epoxidation as key transformations.A short synthesis of the pyrrolophenantridone alkaloid hippadine is described. The approach features the use of a low temperature Ullmann type coupling reaction to effect construction of the pentacyclic skeleton and an unusual methylene oxidation promoted by barium manganate.A simple and direct method for converting thioamides to thioesters through the simple expedient of warming in an aqueous THF solution containing an alkylating reagent is described.