Microwave-assisted diastereoselective two-step three-component synthesis for rapid access to drug-like libraries of substituted 3-amino-β-lactams

Bioorg Med Chem. 2018 Jan 1;26(1):41-49. doi: 10.1016/j.bmc.2017.11.014. Epub 2017 Nov 16.

Abstract

Large, diverse compound libraries are an essential requisite in target-based drug development. In this work, a robust microwave-assisted synthesis for the diastereoselective generation of 3-saccharinyl-trans-β-lactams is reported. The method is optimised for combinatorial library synthesis in which decoration of the scaffold is varied on both the β-lactam and the saccharine moiety. Within the European Lead Factory (ELF) consortium, a library of 263 compounds was efficiently produced using the developed methodology.

Keywords: Library synthesis; Microwave synthesis; Saccharines; Staudinger reaction; β-Lactams.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Combinatorial Chemistry Techniques*
  • Dose-Response Relationship, Drug
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Microwaves*
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Lactams
  • Small Molecule Libraries