Diversity through a branched reaction pathway: generation of multicyclic scaffolds and identification of antimigratory agents

Chemistry. 2011 Jan 10;17(2):649-54. doi: 10.1002/chem.201002195. Epub 2010 Nov 9.

Abstract

A library of 91 heterocyclic compounds composed of 16 distinct scaffolds has been synthesized through a sequence of phosphine-catalyzed ring-forming reactions, Tebbe reactions, Diels-Alder reactions, and, in some cases, hydrolysis. This effort in diversity-oriented synthesis produced a collection of compounds that exhibited high levels of structural variation both in terms of stereochemistry and the range of scaffolds represented. A simple but powerful sequence of reactions thus led to a high-diversity library of relatively modest size with which to explore biologically relevant regions of chemical space. From this library, several molecules were identified that inhibit the migration and invasion of breast cancer cells and may serve as leads for the development of antimetastatic agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Cyclization
  • Female
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Molecular Structure
  • Phosphines / chemistry

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Phosphines
  • phosphine