Synthesis of the C19 methyl ether of aspercyclide A via germyl-Stille macrocyclisation and ELISA evaluation of both enantiomers following optical resolution

Org Biomol Chem. 2011 Oct 7;9(19):6814-24. doi: 10.1039/c1ob05862b. Epub 2011 Aug 15.

Abstract

Aspercyclide A (1) is a biaryl ether containing 11-membered macrocyclic natural product antagonist of the human IgE-FcεRI protein-protein interaction (PPI); a key interaction in the signal transduction pathway for allergic disorders such as asthma. Herein we report a novel approach to the synthesis of the C19 methyl ether of aspercyclide A, employing a Pd(0)-catalysed, fluorous-tagged alkenylgermane/arylbromide macrocyclisation (germyl-Stille reaction) as the key step, and evaluation of both enantiomers of this compound via ELISA following optical resolution by CSP-HPLC. A crystal structure for germyl hydride 27 is also reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry Techniques, Synthetic / methods*
  • Chromatography, High Pressure Liquid
  • Crystallography, X-Ray
  • Cyclization
  • Enzyme-Linked Immunosorbent Assay
  • Lactones / chemical synthesis*
  • Lactones / chemistry
  • Macrocyclic Compounds / chemical synthesis*
  • Macrocyclic Compounds / chemistry
  • Methyl Ethers / chemical synthesis*
  • Methyl Ethers / chemistry
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism

Substances

  • Lactones
  • Macrocyclic Compounds
  • Methyl Ethers
  • aspercyclide A