Piperidine and octahydropyrano[3,4-c] pyridine scaffolds for drug-like molecular libraries of the European Lead Factory

Bioorg Med Chem. 2017 Oct 1;25(19):5160-5170. doi: 10.1016/j.bmc.2017.07.016. Epub 2017 Jul 10.

Abstract

We report short and efficient scalable syntheses of enantiomerically pure (3R,4S)-3-(hydroxymethyl4-(hydroxyethyl))-piperidine and 1-hydroxymethyl-octahydro-1H-pyrano[3,4-c]pyridine scaffolds. The alkaloid core was readily synthesized from naturally occurring quinine and can serve as a valued starting point for drug-discovery. Cleavage of a terminal 1,2-diol and acid catalysed epoxide opening cyclization are the key steps involved. A number of members of a projected small-molecular library is synthesized for each scaffold.

Keywords: 1,3-Amino alcohols; Compound libraries; Nitrogen heterocycles; Non-racemic scaffolds; Quinine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Alcohols / chemical synthesis
  • Amino Alcohols / chemistry
  • Chemistry Techniques, Synthetic / methods
  • Drug Discovery
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Quinine / analogs & derivatives
  • Quinine / chemical synthesis
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry*

Substances

  • Amino Alcohols
  • Piperidines
  • Pyridines
  • Small Molecule Libraries
  • Quinine