Progress toward the Total Synthesis of Goniodomin A: Stereocontrolled, Convergent Synthesis of the C12-C36 Fragment

J Org Chem. 2016 Mar 18;81(6):2213-27. doi: 10.1021/acs.joc.5b02650. Epub 2016 Jan 15.

Abstract

Goniodomin A is a marine polyether macrolide natural product isolated from the dinoflagellate Alexandrium hiranoi. In this paper, we report stereocontrolled, convergent synthesis of a fully functionalized C12-C36 fragment of goniodomin A. The synthesis of the C12-C25 vinylstannane involved a Wittig reaction and a reductive cycloetherification for the construction of the dihydropyran ring. The C26-C36 thioester was synthesized via a Nozaki-Hiyama-Kishi reaction of an aldehyde and an iodoalkyne, the former of which was easily prepared from (R)-malic acid as a chiral source by taking advantage of substrate-controlled diastereoselective reactions. Finally, a palladium-catalyzed coupling of the C12-C25 vinylstannane and the C26-C36 thioester completed the synthesis of the target compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Ethers / chemical synthesis*
  • Ethers / chemistry
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry
  • Molecular Structure
  • Palladium / chemistry
  • Stereoisomerism

Substances

  • Ethers
  • Macrolides
  • goniodomin A
  • Palladium