Synthesis of a unique isoindoline/tetrahydroisoquinoline-based tricyclic sultam library utilizing a Heck-aza-Michael strategy

ACS Comb Sci. 2012 Mar 12;14(3):211-7. doi: 10.1021/co200181x. Epub 2012 Feb 6.

Abstract

The synthesis of a unique isoindoline- and tetrahydroisoquinoline (THIQ)-containing tricyclic sultam library, utilizing a Heck-aza-Michael (HaM) strategy is reported. Both isoindoline and THIQ rings are installed through a Heck reaction on a vinylsulfonamide, followed by one-pot deprotection and intramolecular aza-Michael reaction. Subsequent cyclization with either paraformaldehyde condensation or 1,1'-carbonyldiimidazole coupling generates a variety of tricyclic sultams. Overall, a 160-member library of these sultams, together with their isoindolines/THIQ and secondary sulfonamides precursors, were constructed using this strategy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Combinatorial Chemistry Techniques
  • Cyclization
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Tetrahydroisoquinolines / chemistry*

Substances

  • Small Molecule Libraries
  • Sulfonamides
  • Tetrahydroisoquinolines
  • beta-sultam