Synthesis of the C1-C16 Polyol-containing Macrolactone of 13-desmethyl Lyngbouilloside, an Unnatural Analog of the Originally Assigned Structure of (-)-Lyngbouilloside

摘要

The synthesis of the C1-C16 polyol-containing macrolactone of 13-desmethyl lyngbouilloside, an unnatural analog of the originally assigned structure of (-)-lyngbouilloside is reported. Synthesis of the C1-C16 acyclic backbone is achieved via iterative use of a phosphate tether-mediated one-pot sequential, RCM/CM/chemoselective diimide reduction, with concomitant use of a regio- and diastereoselective cuprate addition using Me2Zn/CuCN .2LiCl or Pd-catalyzed reductive allylic transposition, respectively on bicyclo[4.3.1]phosphate-containing subunits. Subsequent oxidative cleavage and Roskamp homologation completes the pathway to the C1-C16 acyclic fragment. Two routes to the macrocyclic core were explored with mixed success, (i) a Boeckman-type acylketene trapping of the C13 secondary carbinol and (ii) an alternative route employing acid-catalyzed pyran-mixed ketal formation via reaction of the C7 secondary carbinol with the beta-keto ester using trimethylorthoformate, and subsequent Yamaguchi cyclization.