Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products

Bioorg Med Chem. 2017 Feb 1;25(3):921-925. doi: 10.1016/j.bmc.2016.12.005. Epub 2016 Dec 8.

Abstract

A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD).

Keywords: Fragment based drug discovery; Fragment library; Natural product likeness; Natural products; Rearrangement.

MeSH terms

  • Biological Products / chemical synthesis
  • Biological Products / chemistry*
  • Crystallography, X-Ray
  • Cytochalasins / chemical synthesis
  • Cytochalasins / chemistry*
  • Drug Discovery
  • Lactones / chemical synthesis
  • Lactones / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry*

Substances

  • Biological Products
  • Cytochalasins
  • Lactones
  • Small Molecule Libraries
  • Spiro Compounds
  • massarigenin C
  • cytochalasin E