Enantioselective total synthesis of altohyrtin C (spongistatin 2)

Article abstract of DOI:10.1016/S0040-4020(99)00438-X

The first total synthesis of a spongipyran macrolide, altohytrin C, is described. The convergent synthesis strategy relies on a regioselective macrolactonization, a stereoselective Wittig coupling of the two major synthetic fragments, a complex anti aldol reaction to join the C₁-C₁₅ and C₁₆-C₂₈ spiroketal regions, and an anomeric sulfone acylation to join the C₂₉-C₃₇ and C₃₈-C₄₃ pyran regions. The incorporation of the C₄₄- C₅₁ sidechain in the final stages of the synthesis establishes a viable route for the construction of variants in this pharmacologically important region. Methodological developments en route to the total synthesis include a 1,5 antiselective methyl ketone aldol reaction and a diastereoselective approach to Lewis acid mediated β-C-glycosidation. Completion of the synthesis has confirmed the stereochemical assignments proposed in the altohyrtin series and has established the identity of the altohyrtin and spongistatin marine macrolides.