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In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against strain LPTD.
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http://dx.doi.org/10.3390/ijms23126666 | DOI Listing |
Org Biomol Chem
December 2022
Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia.
A new efficient protocol for diastereoselective three-component one-pot lactam synthesis involving the generation of imines the Staudinger/aza-Wittig tandem reaction combined with the Wolff-rearrangement and ketene-imine cycloaddition was developed to produce a series of 24 novel structurally diverse β-lactam- or 1,3-oxazine-products. It was shown that this synthesis can be performed both as a two step-procedure and true MCR with simultaneous loading of all reactants. The intramolecular version of the 1 step provided facile access to seven-membered cyclic imines, which allowed further preparation of a series of rare tricyclic β-lactams.
View Article and Find Full Text PDFACS Omega
October 2022
Department of Chemistry, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait.
The synthesis with structural identifications including NMR and HRMS spectral data along with single-crystal X-ray diffraction analysis (for , , -) of a family of 14 new / bis-4-spiro-β-lactam-based unsaturated macrocycles (,,), obtained by multistep synthesis including (i) diimine formation, (ii) Staudinger [2 + 2] ketene-imine cycloaddition, and (iii) ring-closing metathesis (RCM), is reported.
View Article and Find Full Text PDFInt J Mol Sci
June 2022
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119234 Moscow, Russia.
In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against strain LPTD.
View Article and Find Full Text PDFJ Org Chem
November 2021
Department of Chemistry, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait.
Based on sequential organic transformations, that is, diimine formation, Staudinger [2 + 2] ketene-imine cycloaddition, and ring-closing metathesis (RCM) reactions, the synthesis with full structural identification including NMR and HRMS spectral data along with single X-ray diffraction analysis (for , , , and ) of the first / bis-4-spiro-β-lactams-based azacrown ethers (,,) is reported.
View Article and Find Full Text PDFACS Omega
September 2021
Department of Chemistry, Lomonosov Moscow State University, Leninskie gory 1/3, 119991 Moscow, Russian Federation.
A convenient and versatile one-pot method for synthesis of 1,3-bis-aryl spirooxindolo-β-lactams from isatin Schiff bases and substituted phenylacetic acids using ketene-imine cycloaddition reaction with TsCl for a ketene generation has been developed. The reaction procedure does not require absolute solvents and unstable starting reagents. The studied reactions lead to -diastereoselective β-lactam formation for all tested phenylacetic acids except 4-MeOCHCHCOOH.
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