Diastereoselective synthesis of diverse 3,2′-pyrrolidinyl bispirooxindoles via 1,3-dipolar cycloaddition reactions of azomethine ylides with exocyclic α,β-unsaturated ketones and in silico studies for prediction of bioactivity

Abstract

A three-component highly regio- and diastereoselective 1,3-dipolar cycloaddition reaction between isatin, a series of primary amino acids (10 nos), and exocyclic α,β-unsaturated ketones was developed towards the synthesis of a small library of bispirooxindole (20 nos) at ambient temperature. The developed reaction afforded highly substituted 3,2′-pyrrolidine-bispirooxindole with two vicinal spiro-quaternary and four contiguous stereocenters from the cheap and abundant starting materials. The products were obtained with good to excellent yields (50-95%) and as a single diastereoisomer in the majority of the cases. Primary amino acids were served as amine component for the in-situ generation of azomethine ylides from isatin. Molecular docking studies were carried out to explore the synthesized bispirooxindoles as inhibitors of the epidermal growth factor receptor (EGFR). Two compounds exhibited excellent binding affinity towards EGFR receptor.

Graphical Abstract

Keywords:

• Bispirooxindoles
• 1,3-dipolar cycloaddition
• EGFR receptor
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.