Facile preparation of 3-substituted 2-quinazolinones via electrogenerated base

A new series of 3,4-disubstituted quinazolin-2-ones, with potential T-type calcium channel antagonist activity, and new 4-methylene-quinazolin-2-ones, promising catalysts as N-heterocyclic olefins, have been prepared in good yield by a simple reaction between 2-aminobenzophenone, or 2-aminoacetophenone, and cyanomethyl anion electrogenerated by acetonitrile reduction at a graphite electrode, followed by the addition of different organic isocyanates and subsequent heterocyclization.The authors gratefully acknowledge the financial support of the University of Alcala-project Nº CCG2017/EXP-009

Optimization of PEGylation reaction time and molar ratio of rhG-CSF toward increasing bioactive potency of monoPEGylated protein.

International audiencePEGylation is one of the strategies used for enhancing in vivo residence time of recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF) and therefore reducing in dose frequency to better fit with patient comfort treatment. In this study, three methoxy polyethylene glycol propionaldehydes (mPEG- ALD) of 10, 20 and 30kDa MW were utilized to produce biologically active monoPEGylated rhG-CSF with enhanced molecular weight. PEGylation reactions were carried out at room temperature and pH 5.0 in the presence of cyanoborohydride and two mPEG-ALD: protein molar ratios (3:1 and 5:1). The reactions were monitored with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion chromatography (SEC-HPLC). The results showed that a 2h reaction with 5:1 mPEG-ALD: protein molar ratio was sufficient to direct the reaction toward optimal yields of monoPEGylated protein (86%). Subsequently, isolation of the monoPEGylated forms was successfully achieved. The purified products were compared with respect to their purity (≥95%), identity and isoelectric focusing parameter characteristics. Biological potencies were measured by cell proliferation assay and showed 20.80-42.73% retention of bioactivities. This study highlights the possible improvement of rhG-CSF efficiency by PEGylation. Further studies will investigate in vitro and in vivo immunogenicity and toxicity of monoPEGylated conjugates

Reduction of 1,2-dicarbonyl compounds and of their N-phenylimine derivatives by sodium cyanide under aprotic conditions

Some aromatic 1,2-dicarbonyl compounds, i.e. 9,10-phenanthrenequinone, acenaphthenequinone and benzil, and their corresponding N-phenyl monoimines, have been reduced, using dry acetonitrile as the solvent, in the presence of sodium cyanide as a reducing agent. Comparative potentiostatic preparative-scale electrolysis is described.The authors gratefully acknowledge the financial support of the University of Alcala – project No. CCG2014/EXP-010. K. Hamrouni thanks the Tunisian Ministry of Science that provided her a grant ‘‘bourse d’alternance’’ as financial support of her stay in Spain

Stereoselective Cyclopropanation to Homoquinones from Phenacyl Carbenes Obtained through Quinone-Electrogenerated Bases

A series of new (<i>E</i>) and (<i>Z</i>)-benzoyl-homoquinones have been prepared in good yield by the parent quinone-electrogenerated base (EGB) in the presence of α-bromoacetophenones or α-bromopropiophenone. The EGB, obtained when electrolysis of <i>p</i>-benzoquinone, or 1,4-naphthoquinone, is carried out at the reduction potential of their first voltammetric peak, conducted to electrogenerated phenacyl carbenes after halide evolution on the first obtained bromo-enolates. The stereoselectivity of the [2 + 2]­cycloaddition of the carbene to the quinoid substrate is highly dependent on the electrode nature. Reaction mechanism proposal is discussed

EGB-promoted electrochemical synthesis of 6-thioxo-[1,3,5]-triazinane-2,4 dione derivatives

<p>A simple method for the synthesis of 6-thioxo-[1,3,5]-triazinane-2,4-dione derivatives was reported. The electrogenerated cyanomethyl base obtained from electroreduction of neat acetonitrile assisted the reaction between thiourea derivatives and alkyl or aryl isocyanate. This protocol had the advantage of giving good yields using mild conditions. The obtained products have been identified by spectroscopic data, mass spectrometry, and high-resolution mass spectra or elemental analysis.</p