I. Studies Towards the Total Synthesis of (+)-Iriomoteolide-1a II. Asymmetric S(E)' Reactions of E/Z-alpha,beta-Unsaturated Aldehydes.

摘要

Iriomoteolide-1a is a unique marine macrolide isolated in 2007 which displays potent anti-cancer activity. Studies toward the total synthesis of this natural product are presented which culminated in the synthesis of a major portion of the molecule from three smaller fragments. These studies utilize a stereoselective organozinc reaction and a stereoselective hydroboration followed by a B-alkyl Suzuki-Miyaura cross-coupling to set a several key stereocenters and form key bonds in the natural product. Two major fragments of the molecule were united via an ester bond linkage through the addition of an alkynyl anion to an activated carbonyl species. Efforts are discussed outlining the attempts for coupling of the final fragment and plans for macrocyclization.;A novel method for the synthesis of chiral allylic alcohols has been developed utilizing asymmetric SE' reactions of (E) and (Z)-&agr;,beta-unsaturated aldehydes bearing gamma-stereocenters. Reactions of aldehyde substrates with chiral allyl borolidines display unanticipated properties of matched and mismatched stereoselection resulting from the gamma-stereocenter and the chiral auxiliary of the nonracemic borolidine reagent. A model was devised to explain the observed stereoinduction and computations were undertaken utilizing density functional theory to provide valuable insights into this asymmetric process as well as to guide further reaction development.