Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp(3)-rich library

Bioorg Med Chem. 2015 Jun 1;23(11):2621-8. doi: 10.1016/j.bmc.2014.12.050. Epub 2014 Dec 29.

Abstract

The application of a tandem condensation/cyclisation/[3+2]-cycloaddition/elimination reaction gives an sp(3)-rich tricyclic pyrazoline scaffold with two ethyl esters in a single step from a simple linear starting material. The successive hydrolysis and cyclisation (with Boc anhydride) of these 3-dimensional architectures, generates unprecedented 16-membered macrocyclic bisanhydrides (characterised by XRD). Selective amidations could then be achieved by ring opening with a primary amine followed by HATU-promoted amide coupling to yield an sp(3)-rich natural product-like library.

Keywords: Cycloaddition; Library; Macrocycle; Natural product-like; Scaffold; Tandem; Two-directional; sp(3)-rich.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Biological Products / chemical synthesis*
  • Catalysis
  • Cyclization
  • Cycloaddition Reaction
  • Drug Discovery*
  • Macrocyclic Compounds / chemical synthesis*
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis*

Substances

  • Amines
  • Biological Products
  • Macrocyclic Compounds
  • Small Molecule Libraries