Chemistry of withaferin-A: chemo, regio, and stereoselective synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A via one-pot three-component [3+2] azomethine ylide cycloaddition and their cytotoxicity evaluation.
Withaferin-A (WA) has attracted the attention of chemists as well as biologists due to its interesting structure and various bio-activities. In light of the promising biological importance of WA as well as pyrrolidine-2-spiro-3'-oxindole ring system, we became interested in the synthesis of a combined motif involving both the ring systems via the 1,3-dipolar cycloaddition of WA at Δ(2)-bond of the α,β-unsaturated carbonyl system. We now report a facile, atom-economic synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A (10 compounds) via the intermolecular cycloaddition of azomethine ylides generated in situ from proline and isatins/acenaphthoquinone. The reaction is highly chemo, regio, and stereoselective affording the cis-fused products with β-orienting hydrogen. The structures were determined by 1D/2D NMR spectroscopic data analysis and unequivocally confirmed by X-ray crystallographic analysis in some cases. Bioevaluation of the compounds against six cancer lines (e.g., CHO, HepG2, HeLa, HEK 293, MDCK-II, and Caco-2) identified 4 promising potential anticancer compounds.
Department of Chemistry, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700 032, India.
Yogesh P
YP
Bharitkar
Satish
S
Kanhar
Neradibilli
N
Suneel
Susanta Kumar
SK
Mondal
Abhijit
A
Hazra
Nirup B
NB
Mondal
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D061565:Cycloaddition Reaction; D006801:Humans; D007211:Indoles; D008968:Molecular Conformation; D015394:Molecular Structure; D000078183:Oxindoles; D013141:Spiro Compounds; D013237:Stereoisomerism; D054358:Withanolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D007211:Indoles; D000078183:Oxindoles; D013141:Spiro Compounds; D054358:Withanolides; C022960:2-oxindole; C009684:withaferin A