14661-69-9Relevant articles and documents
Homologation of Electron-Rich Benzyl Bromide Derivatives via Diazo C-C Bond Insertion
Modak, Atanu,Alegre-Requena, Juan V.,De Lescure, Louis,Rynders, Kathryn J.,Paton, Robert S.,Race, Nicholas J.
supporting information, p. 86 - 92 (2021/12/27)
The ability to manipulate C-C bonds for selective chemical transformations is challenging and represents a growing area of research. Here, we report a formal insertion of diazo compounds into the "unactivated"C-C bond of benzyl bromide derivatives catalyzed by a simple Lewis acid. The homologation reaction proceeds via the intermediacy of a phenonium ion, and the products contain benzylic quaternary centers and an alkyl bromide amenable to further derivatization. Computational analysis provides critical insight into the reaction mechanism, in particular the key selectivity-determining step.
Synthesis of 4-substituted-3-Hydroxyquinolin-2(1H)-ones with anticancer activity
Paterna, Roberta,Padanha, Rita,Russo, Roberto,Frade, Raquel F.M.,Faustino, Hélio,Gois, Pedro M.P.
supporting information, (2020/02/11)
Herein we show that the 3-hydroxyquinolin-2(1H)-one (3HQ) core is a suitable platform to develop new compounds with anticancer activity against MCF-7 (IC50 up to 4.82 μM) and NCI–H460 (IC50 up to 1.8 μM) cancer cell lines. The ring-expansion reaction of isatins with diazo esters catalysed by di-rhodium (II) complexes proved to be a simple and effective strategy to synthesize 4-carboxylate-3HQs (yields up to 92%). 4-Carboxamide-3HQs were more efficiently prepared using NHS-diazoacetate in yields up to 88%. This innovative methodology enabled the construction of “peptidic-like” 3HQs, with several amino acid substituents. Among this series, the L-leucine derivative induced the cell death of MCF-7 (IC50 of 15.1 μM) and NCI–H460 (IC50 of 2.7 μM) cancer cell lines without causing any appreciable cytotoxicity against the non-cancer cell model (CHOK1).
Engineering Boron Hot Spots for the Site-Selective Installation of Iminoboronates on Peptide Chains
Russo, Roberto,Padanha, Rita,Fernandes, Fábio,Veiros, Luis F.,Corzana, Francisco,Gois, Pedro M. P.
supporting information, p. 15226 - 15231 (2020/10/20)
Boronic acids (BAs) are a promising bioconjugation function to design dynamic materials as they can establish reversible covalent bonds with oxygen/nitrogen nucleophiles that respond to different pH, ROS, carbohydrates and glutathione levels. However, the dynamic nature of these bonds also limits the control over the stability and site-selectivity of the bioconjugation, which ultimately leads to heterogeneous conjugates with poor stability under physiological conditions. Here we disclose a new strategy to install BAs on peptide chains. In this study, a “boron hot spot“ based on the 3-hydroxyquinolin-2(1H)-one scaffold was developed and upon installation on a peptide N-terminal cysteine, enables the site-selective formation of iminoboronates with 2-formyl-phenyl boronic acids (Ka of 58128±2 m?1). The reaction is selective in the presence of competing lysine ?-amino groups, and the resulting iminoboronates, displayed improved stability in buffers solutions and a cleavable profile in the presence of glutathione. Once developed, the methodology was used to prepare cleavable fluorescent conjugates with a laminin fragment, which enabled the validation of the 67LR receptor as a target to deliver cargo to cancer HT29 cells.
