Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone Motif-Fused 3,3'-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition Reaction

Molecules. 2017 Apr 17;22(4):645. doi: 10.3390/molecules22040645.

Abstract

Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3'-pyrrolidinyl-dispirooxindoles 3-5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products bearing four or three consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable application of this method was for the design of new hybrid architectures for biological screening through the adequate fusion of these sub-units of turmerone and 3,3'-pyrrolidinyl-dispirooxindole, generating drug-like molecules.

Keywords: 1,3-dipolar cycloaddition reaction; azomethine ylides; diastereoselectivity; turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles; vicinal spiroquaternary stereocenters.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cycloaddition Reaction*
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure

Substances

  • Antineoplastic Agents
  • Indoles