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

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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.

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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.

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Singh, M., Amrutha Krishnan, A.V., Mandal, R. et al. Azomethine ylide cycloaddition: a versatile tool for preparing novel pyrrolizidino-spiro-oxindolo hybrids of the doubly conjugated alkamide piperine. Mol Divers 24, 627–639 (2020). https://doi.org/10.1007/s11030-019-09969-w

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