Bernard Côté

ENANTIOSELECTIVE TOTAL SYNTHESIS OF ALTOHYRTIN C (SPONGISTATIN 2)

Abstract The first total synthesis of a spongipyran macrolide, altohyrtin 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 anti-selective 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.

Addition of allylstannanes to glycal epoxides. A diastereoselective approach to β-C-glycosidation

Abstract A new method for the synthesis of β - C -allyl glycosides has been developed for use in the synthesis of the spongipyran macrolides. Functionalized dihydropyrans are transformed to cis tetrahydropyrans via a two step process: i) epoxidation using dimethyldioxirane and ii) Lewis acid mediated epoxide opening with allylstannanes as nucleophiles. This protocol, which can be successfully applied to complex systems, augments the limited body of methodology available for the preparation of β-configured C -glycosides.