Total synthesis of (+)-azaspiracid-1. An exhibition of the intricacies of complex molecule synthesis

J Am Chem Soc. 2008 Dec 3;130(48):16295-309. doi: 10.1021/ja804659n.

Abstract

The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels-Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyama aldol reaction to deliver the FG-ring fragment. The subsequent fragment couplings were accomplished by aldol and sulfone anion methodologies. All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehydes / chemistry
  • Anions / chemistry
  • Carbon / chemistry
  • Catalysis
  • Chelating Agents / chemistry
  • Iodine Compounds / chemical synthesis
  • Iodine Compounds / chemistry
  • Magnetic Resonance Spectroscopy
  • Marine Toxins / chemical synthesis*
  • Marine Toxins / chemistry
  • Methylation
  • Models, Molecular
  • Molecular Structure
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Stereoisomerism
  • Sulfones / chemistry
  • Vinyl Compounds / chemistry

Substances

  • Aldehydes
  • Anions
  • Chelating Agents
  • Iodine Compounds
  • Marine Toxins
  • Spiro Compounds
  • Sulfones
  • Vinyl Compounds
  • azaspiracid
  • Carbon