Approach toward the total synthesis of griseoviridin: formation of thioethynyl and thiovinyl ether-containing nine-membered lactones through a thioalkynylation-macrolactonization-hydrostannylation sequence

J Org Chem. 2002 Jun 28;67(13):4565-8. doi: 10.1021/jo0103120.

Abstract

Synthesis of the lactone core 17 of 8-epi-griseoviridin is reported. Thioethynyl derivative 11 was easily prepared via an anionic coupling reaction between acetylenic compound 9 and sulfone 10. After desilylation of 11, saponification of the resulting hydroxy ester 12 followed by a Mitsunobu macrolactonization furnished the unusual triple-bond-containing nine-membered lactone 13 in 50% yield for the last two steps (39% after recrystallization). Stannylation under Magriotis conditions led to the pure regio- and stereocontrolled vinyltin 14 (80% yield). After a Sn/I exchange, palladium-catalyzed carbonylation delivered either the ester lactone 16 in 67% yield or the propargyl amide 17 in 65% yield. Synthesis of propargyl amide 17 of the lactone core of 8-epi-griseoviridin was achieved in 11.9% overall yield from commercial L-cystin dimethyl ester (nine steps).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Catalysis
  • Chemistry, Organic / methods
  • Chromatography, Thin Layer
  • Lactones / chemical synthesis*
  • Lactones / chemistry*
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides*
  • Sulfur Compounds / chemical synthesis
  • Sulfur Compounds / chemistry
  • Tin Compounds / chemistry
  • Vinyl Compounds / chemical synthesis
  • Vinyl Compounds / chemistry

Substances

  • Anti-Bacterial Agents
  • Lactones
  • Peptides
  • Sulfur Compounds
  • Tin Compounds
  • Vinyl Compounds
  • griseoviridin