Asymmetric Total Synthesis of (-)-Englerin A through Catalytic Diastereo- and Enantioselective Carbonyl Ylide Cycloaddition

Chemistry. 2015 Aug 10;21(33):11671-6. doi: 10.1002/chem.201502009. Epub 2015 Jul 15.

Abstract

An asymmetric total synthesis of the guaiane sesquiterpene (-)-englerin A, a potent and selective inhibitor of the growth of renal cancer cell lines, was accomplished. The basis of the approach is a highly diastereo- and enantioselective carbonyl ylide cycloaddition with an ethyl vinyl ether dipolarophile under catalysis by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], [Rh2 (S-TCPTTL)4 ], to construct the oxabicyclo[3.2.1]octane framework with concomitant introduction of the oxygen substituent at C9 on the exo-face. Another notable feature of the synthesis is ruthenium tetraoxide-catalyzed chemoselective oxidative conversion of C9 ethyl ether to C9 acetate.

Keywords: (−)-englerin A; 1,3-dipolar cycloaddition; asymmetric synthesis; carbonyl ylide; dirhodium(II) complexes; total synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biological Factors / chemistry
  • Catalysis
  • Cell Line, Tumor
  • Coordination Complexes / chemistry*
  • Cycloaddition Reaction
  • Ethyl Ethers / chemistry*
  • Humans
  • Kidney Neoplasms / chemistry*
  • Kidney Neoplasms / pathology
  • Molecular Structure
  • Rhodium / chemistry
  • Sesquiterpenes, Guaiane / chemical synthesis*
  • Sesquiterpenes, Guaiane / chemistry
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Biological Factors
  • Coordination Complexes
  • Ethyl Ethers
  • Sesquiterpenes, Guaiane
  • dirhodium(II) tetrakis(N-tetrachlorophthaloyl-(S)-tert-leucinate)
  • englerin A
  • Rhodium