Preparation of precursors for the synthesis of the C18–C28 fragment of Iriomoteolide-2a.

Abstract

Marine dinoflagellates of the genus Amphidinium produce a great diversity of secondary metabolites, among them macrolides with very diverse and interesting structures, such as Amphidinolides and Iriomoteolides. These metabolites have potent anticancer activity, a fact that, together with their low availability from natural resources, makes them interesting targets for total synthesis in order to further study and evaluate their biological activity. Iriomoteolide-2a is a potent cytotoxic 23-membered macrolide of polyketide origin. This macrolide contains 11 stereogenic centers and features a structurally complex side chain. To date, only the structure of iriomoteolide-2a is known. No total synthesis has been reported yet. The retrosynthesis designed in the group for Iriomoteolide-2a disconnects the molecule into two major fragments (Scheme S1). This TFG focuses on the preparation of precursors that can be applied to the stereoselective preparation of the C18–C28 fragment.Two routes have been proposed for the synthesis of the C18–C28 fragment as shown in Scheme S2.In this work ketone A has been prepared following the route shown in Scheme S3a. Its dihydroxylation under different conditions has been studied. TBS-protected vinyl bromide I has also been prepared following the route shown in Scheme S3b. Finally, the first steps towards the preparation of ketone II have been explored (Scheme S3c).