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Azomethine ylide cycloaddition: a versatile tool for preparing novel pyrrolizidino-spiro-oxindolo hybrids of the doubly conjugated alkamide piperine

  • Meenakshi Singh
  • A. V. Amrutha Krishnan
  • Ramkrishna Mandal
  • Jayanta Samanta
  • V. Ravichandiran
  • Ramalingam Natarajan
  • Yogesh P. BharitkarEmail author
  • Abhijit HazraEmail author
Original Article
  • 22 Downloads

Abstract

A facile, multicomponent (MCR) atom-economic synthesis of novel spiro-oxindolo pyrrolizidine adducts of piperine has been achieved via an intermolecular 1,3-dipolar azomethine ylide cycloaddition reaction. Either of the two conjugated double bonds in piperine takes part in the reaction to produce two regioisomeric adducts in racemic form. Acenaphthoquinone, ninhydrin and different isatin derivatives were reacted with proline and piperine to afford a never before reported library of 22 compounds. The structures of the products were determined by 1D/2D NMR, mass spectral analysis and confirmed by X-ray crystallography of selected products. Chiral HPLC separation was performed to measure the specific rotation and CD spectra of the enantiomers for two racemic compounds.

Graphic abstract

Keywords

Piperine Azomethine ylide cycloaddition Spiro-oxindolo pyrrolizidine Chiral HPLC 

Notes

Acknowledgements

A.H and B.Y. are recipients of Research Fellowships in the form of Young Scientist Grant (YSS/2015/001141) and NPDF/2016/000088 from SERB-DST, India. M.S., A.K. and R.M. thank DOP, Ministry of Chemical and Fertilizers, Govt. of India, for providing fellowship. We also thank R. Gajbhiye of NIPER for his assistance in acquiring HRMS spectra and YMC India Pvt. Ltd for providing CHIRAL Cellulose-C column. Our thanks are due to Director NIPER and IICB for giving laboratory and instrumental facility, and to Drs. N.B. Mondal and B. Achari (Ex-Emeritus Scientist, CSIR-IICB) for helpful suggestions.

Supplementary material

11030_2019_9969_MOESM1_ESM.pdf (23.8 mb)
Supplementary material 1 (PDF 24409 kb)
11030_2019_9969_MOESM2_ESM.pdf (272 kb)
Supplementary material 2 (PDF 271 kb)

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.National Institute of Pharmaceutical Education and Research (NIPER), Chunilal BhawanKolkataIndia
  2. 2.Department of Organic and Medicinal ChemistryIndian Institute of Chemical Biology, Council of Scientific and Industrial ResearchKolkataIndia

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