Revisiting Biginelli-like reactions: solvent effects, mechanisms, biological applications and correction of several literature reports.

Autor: Beck PS; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Leitão AG; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Santana YB; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Correa JR; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Rodrigues CVS; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Machado DFS; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Matos GDR; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Ramos LM; Universidade Estadual de Goiás (UEG), Anápolis, Goiás, 75001-970, Brazil., Gatto CC; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Oliveira SCC; University of Brasilia, Institute of Biology, Laboratory of Allelopathy, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil., Andrade CKZ; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com., Neto BAD; University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com.
Jazyk: angličtina
Zdroj: Organic & biomolecular chemistry [Org Biomol Chem] 2024 May 08; Vol. 22 (18), pp. 3630-3651. Date of Electronic Publication: 2024 May 08.
DOI: 10.1039/d4ob00272e
Abstrakt: This study critically reevaluates reported Biginelli-like reactions using a Kamlet-Abboud-Taft-based solvent effect model. Surprisingly, structural misassignments were discovered in certain multicomponent reactions, leading to the identification of pseudo three-component derivatives instead of the expected MCR adducts. Attempts to replicate literature conditions failed, prompting reconsideration of the described MCRs and proposed mechanisms. Electrospray ionization (tandem) mass spectrometry, NMR, melting points, elemental analyses and single-crystal X-ray analysis exposed inaccuracies in reported MCRs and allowed for the proposition of a complete catalytic cycle. Biological investigations using both pure and "contaminated" derivatives revealed distinctive features in assessed bioassays. A new cellular action mechanism was unveiled for a one obtained pseudo three-component adduct, suggesting similarity with the known dihydropyrimidinone Monastrol as Eg5 inhibitors, disrupting mitosis by forming monoastral mitotic spindles. Docking studies and RMSD analyses supported this hypothesis. The findings described herein underscore the necessity for a critical reexamination and potential corrections of structural assignments in several reports. This work emphasizes the significance of rigorous characterization and critical evaluation in synthetic chemistry, urging a careful reassessment of reported synthesis and biological activities associated with these compounds.
Databáze: MEDLINE
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