The solid-phase Zincke reaction: preparation of omega-hydroxy pyridinium salts in the search for CFTR activation

J Org Chem. 2000 Aug 25;65(17):5131-5. doi: 10.1021/jo0001636.

Abstract

A study of structural modifications of MPB-07 was undertaken as part of a synthetic program aimed at discovering small molecules with CFTR activation potential. Solid-phase synthesis techniques were used to prepare derivatives of MPB-07 employing the Zincke reaction for the construction of aromatic, quaternary ammonium salts such as those found in 2 or 3. In this transformation, primary amines react with highly electrophilic N-2,4-dinitrophenylpyridinium (DNP) salt 4 to afford pyridinium salt 8 with release of 2,4-dinitroaniline 6. Thus, the reaction of 1-(2,4-dinitrophenyl)pyridinium salts with various polymer-bound amino ethers, followed by cleavage from the resin, delivers the desired salts in good yield and high purity.

Publication types

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

MeSH terms

  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry*
  • Magnetic Resonance Spectroscopy
  • Pyridinium Compounds / chemistry*

Substances

  • Pyridinium Compounds
  • Cystic Fibrosis Transmembrane Conductance Regulator