Stereocontrolled elaboration of natural (-)-polycavernoside A, a powerfully toxic metabolite of the red alga Polycavernosa tsudai

A stereoselective total synthesis of natural levorotatory polycavemoside A (1) has been achieved. initial investigations produced the properly activat ed disaccharide unit 18b via the conjoining of building blocks originating from L-fucose and D-xylose. This objective was followed by preparation of t he phenylsulfonyl-substituted tetrahydropyran 23 and aldehyde 30. After pro per linking of these key compounds, important information had to be garnere d on the sequence of steps that would ultimately result in successful acces s to 1. Although oxidation to generate alpha-diketone 35 and unmasking of t he C-13 hydroxyl did give rise efficiently to lactol 36, this functionality did not pave the way for ensuring macrolactonization. When this sequence o f steps was reversed, it was indeed possible to arrive at the heavily funct ionalized precursor 43. However, numerous experiments failed to result in t he requisite activation of C-16 for attachment of the trienyl side chain. H owever, if the E-vinyl iodide was elaborated in advance of alpha-diketone g eneration, glycosidation, and complete side chain construction, arrival at 1 proceeded without unsurmountable complications to furnish the targeted ma rine toxin.