Efforts towards the asymmetric total synthesis of (–)-13-desmethyllyngbouilloside, an unnatural analog of lyngbouilloside will be discussed. The key reactions involved in the syntheses of (–)-13-desmethyl-lyngbouilloside are iterative one-pot sequential RCM/CM/chemoselective hydrogenation, regio- and diastereoselective cuprate addition, a one-pot sequential Pd-catalyzed reductive allylic transposition/methylation/phosphate tether removal, Roskamp homologation and Boeckman acyl-ketene cyclization to accomplish the synthesis of macrocyclic core of (–)-13-desmethyllyngbouilloside. This efficient, pot-economical and library amenable approach is further extended for the syntheses of diverse and structurally related analogs library of (–)-lyngbouilloside and (+)-neopeltolide. Towards this goal, an iterative regio- and diastereoselective cuprate addition and late stage alcohol functionalization followed by RCM/deprotection sequence enables the syntheses of a diverse range of α,β-unsaturated macrocycles bearing carbon-, sulfur- and phosphorus warheads. These analogs will be submitted to our collaborators for biological screening.

Phosphate tether-mediated approach for the efficient syntheses of 13-desmethyl-lyngbouilloside and simplified analogs

254th National Meeting (2017)

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