RESUMO
On December 12th, 2023, the European Commission took regulatory action to amend Annex XVII of REACH, imposing restrictions on the use of N,N-dimethylformamide (DMF) within the EU market owing to its high toxicity. Historically, DMF has been widely considered the gold standard for solid-phase peptide synthesis (SPPS). Being urgent to propose alternative solvents, we tested the suitability of non-hazardous neat and mixed solvents. Notably, binary solvent mixtures containing dimethyl sulfoxide as one of the solvent partners demonstrated high efficacy in solubilizing reagents while maintaining the desired swelling characteristics of common resins. A series of binary solvent mixtures were tested in automated SPPS, both at room temperature and high temperature, employing the PurePep® Chorus synthesizer, which enabled controlled induction heating between 25 and 90°C with oscillation mixing. The performances were assessed in challenging peptide sequences, i.e., ACP (65-74), and in longer and aggregating sequences like SARS-CoV-2 RBM (436-507) and ß-amyloid (1-42). Furthermore, as part of the proposed sustainable approach to minimize the utilization of hazardous solvents, we coupled the novel PurePep EasyClean catch-and-release purification technology. This work, addressing regulatory compliance, emphasizes the crucial role of green chemistry in advancing safer and more environmentally friendly practices in SPPS.
RESUMO
The first immobilization of a MacMillan's first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a-c was tested in the asymmetric Friedel-Crafts alkylation of N-methylpyrrole with α,ß-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles.
RESUMO
A convenient synthesis of 1,2,3-thiadiazoles and 1,2,3-selenadiazoles was achieved using an ionic liquid as a novel soluble support. Ionic liquid-supported sulfonyl hydrazine was synthesized and reacted with a number of ketones to afford the corresponding ionic liquid-supported hydrazones that were converted to 1,2,3-thiadiazoles in the presence of thionyl chloride. The reaction of ionic liquid-supported hydrazones with selenium dioxide in acetonitrile afforded 1,2,3-selenadiazoles. The advantages of this methodology were the ease of workup, simple reaction conditions, and high purity.
Assuntos
Líquidos Iônicos/química , Compostos Organosselênicos/síntese química , Tiadiazóis/síntese química , Estrutura Molecular , Compostos Organosselênicos/química , Solubilidade , Tiadiazóis/químicaRESUMO
The paper describes synthesis of a novel ionic liquid-supported sulfonyl azide and its applications as diazotransfer reagent of active methylene compounds as well as deformylative diazo transfer reagent. The diazo compounds were isolated in excellent yields (82-94%) and high purity. The method offers better separation of product and reagent. This method is experimentally simple and mild, and requires very short reaction time.