| Investigation into the reactivity of an arylhexatrienoate led to the discovery of a new cycloisomerization. This novel Lewis acid catalyzed reaction converted the starting material into a bicyclo[3.1.0]hex-2-ene, was found to be stereospecific, and was shown to be efficient for both aryl- and vinylhexatrienoates. The reaction was showcased as the key step in the total synthesis of (+/-)-photodeoxytridachione and (-)-crispatene, two members of a large family of polyketides isolated from sacoglossan molluscs. The synthesis of (-)-crispatene established the absolute stereochemistry of the natural product. An improved, modular and convergent route to the entire family of molluscan polyketides led to the total synthesis of cyercene A, placidene A and B, isoplacidene A and B, and (+/-)-deoxytridachione. In the synthesis of deoxytridachione, two bicyclo[4.2.0]octadiene isomers of deoxytridachione were also prepared. Three months later, one of these octadienes was reported in the literature as a natural product isolated from a sacoglossan mollusc. We subsequently developed a rational approach to this natural product, ocellapyrone A, and its close congener, ocellapyrone B.; The total synthesis of two closely related diterpenoids, (-)-heptemerone B and (-)-guanacastepene E, was also completed. The synthesis relies on a stereoselective cuprate conjugate addition of two enantiomerically enriched partners. One partner, a cyclopentenone, was assembled through a stereoselective Whitesell-ene reaction and subsequent ring-closing metathesis. Once the two partners were coupled, the central seven-membered ring of the natural products was closed using a Moeller-Wright electrochemical oxidation. Careful differentiation and manipulation of the resulting secondary hydroxyl groups led to the successful synthesis of the two natural products, confirming the absolute stereochemistry of the heptemerones. |
