Recent achievements and current trajectories of diversity-oriented synthesis

Christopher J Gerry; Stuart L Schreiber

doi:10.1016/j.cbpa.2019.08.008

Recent achievements and current trajectories of diversity-oriented synthesis

Curr Opin Chem Biol. 2020 Jun:56:1-9. doi: 10.1016/j.cbpa.2019.08.008. Epub 2019 Oct 15.

Authors

Christopher J Gerry¹, Stuart L Schreiber²

Affiliations

¹ Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Chemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
² Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Chemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. Electronic address: [email protected].

PMID: 31622927
DOI: 10.1016/j.cbpa.2019.08.008

Abstract

For two decades, diversity-oriented synthesis (DOS) has facilitated the assembly of small-molecule libraries comprising a variety of complex molecular architectures. Here, we describe some of the recent achievements in this field, many of which promise to contribute to the development of new chemical probes and drug leads. In particular, we report progress along several avenues of bioactive discovery that leverage topographically complex compounds generated using DOS and other methods. We also discuss advances in DNA-compatible chemistry that enable syntheses of more three-dimensionally complex and diverse DNA-encoded libraries. Continual innovation in organic chemistry will be required to both expand and exploit our understanding of biological systems.

Publication types

Review

MeSH terms

Catalysis
Chemistry Techniques, Synthetic / methods*
Combinatorial Chemistry Techniques
Cycloaddition Reaction
DNA / chemistry
Gene Library
Molecular Structure
Polymerization
Small Molecule Libraries / chemical synthesis*

Substances

Small Molecule Libraries
DNA