Semi-synthesis of a novel hybrid isoxazolidino withaferin via chemoselective and diastereoselective 1,3-dipolar nitrone cycloaddition reaction

Ramkrishna Mandal; Meenakshi Singh; Amrutha A V Krishnan; Yogita H Dahat; Yogesh P Bharitkar; V Ravichandiran; Abhijit Hazra

doi:10.1080/14786419.2019.1582045

Semi-synthesis of a novel hybrid isoxazolidino withaferin via chemoselective and diastereoselective 1,3-dipolar nitrone cycloaddition reaction

Nat Prod Res. 2020 Aug;34(15):2208-2218. doi: 10.1080/14786419.2019.1582045. Epub 2019 Apr 2.

Authors

Ramkrishna Mandal¹, Meenakshi Singh¹, Amrutha A V Krishnan¹, Yogita H Dahat¹, Yogesh P Bharitkar¹, V Ravichandiran¹, Abhijit Hazra¹

Affiliation

¹ National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, India.

PMID: 30938170
DOI: 10.1080/14786419.2019.1582045

Abstract

A facile, atom-economic synthesis of isoxazilidino withaferin, a novel hybrid of withaferin A, has been accomplished via two-step reaction of nitrone synthesis followed by nitrone 1,3-dipolar cycloaddition. The reaction is highly chemoselective (preferential reaction only on one of the two double bonds present on withaferin A) and diastereoselective affording exclusively the cis-fused products. The structure was determined by detailed analysis of 1D, 2D NMR and mass spectral data.

Keywords: 2D NMR (HSQC; COSY; HMBC; NOESY); Withaferin A; isoxazolidine; nitrone-cycloaddition; semi-synthesis.

MeSH terms

Cycloaddition Reaction*
Isoxazoles / chemical synthesis*
Molecular Structure
Nitrogen Oxides / chemistry*
Spectrum Analysis
Stereoisomerism
Withanolides / chemical synthesis*
Withanolides / chemistry

Substances

Isoxazoles
Nitrogen Oxides
Withanolides
nitrones
withaferin A