Fused Ring Molecular Scaffold with 3D Architecture for Constrained Peptidomimetics: Polymer-Supported Stereoselective Synthesis of Tetrahydrobenzo[e]pyrazino[2,1-c][1,2,4]thiadiazinone 6,6-dioxide via N-Acyl Iminiums

ACS Comb Sci. 2016 Oct 10;18(10):655-659. doi: 10.1021/acscombsci.6b00126. Epub 2016 Sep 23.

Abstract

3,4,4a,5-Tetrahydrobenzo[e]pyrazino[2,1-c][1,2,4]thiadiazin-1(2H)-one 6,6-dioxides, molecular scaffolds with 3D architecture, were synthesized on solid supports via tandem N-acyl iminium ion cyclization followed by nucleophilic addition. The modular synthesis proceeded under mild conditions using commercially available building blocks and provided crude products with respectable purity. The synthesized compounds are applicable as fused nitrogenous heterocyclic compounds in drug discovery and as constrained peptidomimetics incorporated into a peptide backbone.

Keywords: 3D architecture; drug discovery; modular synthesis; molecular scaffolds; peptidomimetics; solid supports.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic S-Oxides / chemical synthesis*
  • Cyclization
  • Heterocyclic Compounds, 3-Ring / chemical synthesis*
  • Imines / chemical synthesis*
  • Peptides / chemistry
  • Peptidomimetics / chemical synthesis*
  • Polymers / chemistry*
  • Stereoisomerism

Substances

  • Cyclic S-Oxides
  • Heterocyclic Compounds, 3-Ring
  • Imines
  • Peptides
  • Peptidomimetics
  • Polymers