Functionalized Spiroindolines with Anticancer Activity through a Metal-Free Post-Ugi Diastereoselective One-Pot Cascade Reaction

Chemistry. 2018 May 7;24(26):6732-6736. doi: 10.1002/chem.201801081. Epub 2018 Apr 20.

Abstract

A post-Ugi diastereoselective one-pot cascade reaction requiring no metal catalyst was developed. The reaction scope was wide with mild conditions and good yields. A collection of spiroindolines was prepared by the protocol and screening tests in several difficult-to-inhibit cancer cell lines were conducted. The relationship of structure and anticancer activities was promising and in the Huh7 cell lines compound 16 j is more potent than Vinbalstine. The cyclization design strategy could be applicable to other multicomponent reactions (MCRs) for synthesizing bioactive and drug-like heterocycles.

Keywords: Ugi reaction; cyclization reactions; multicomponent reactions; spiroindolines; synthetic methods.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Cyclization
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Metals / chemistry
  • Molecular Conformation
  • Spiro Compounds / chemistry*
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Indoles
  • Metals
  • Spiro Compounds
  • indoline