Construction of a bicyclic beta-benzyloxy and beta-hydroxy amide library through a multicomponent cyclization reaction

J Comb Chem. Jul-Aug 2009;11(4):640-4. doi: 10.1021/cc800200h.

Abstract

In this manuscript, we describe the synthesis of a bicyclic beta-benzyloxy and beta-hydroxy amide library from cyanohydrin ethers. The benzyloxy amides were prepared through a one-pot sequence of hydrozirconation, acylation, and intramolecular Friedel-Crafts alkylation. Selected benzyl ethers were converted to alcohols by hydrogenolysis in a continuous flow reactor. Chemistry space BCUT metrics and 2D fingerprint similarity calculations showed that these compounds contribute chemical diversity value to existing chemical libraries.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry
  • Combinatorial Chemistry Techniques / methods*
  • Cyclization
  • Ethers / chemistry
  • Molecular Structure
  • Nitriles / chemistry
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry

Substances

  • Amides
  • Bridged Bicyclo Compounds
  • Ethers
  • Nitriles
  • Small Molecule Libraries
  • cyanohydrin