Department of Chemistry, Faculty of Science, University of Alexandria P.O. Box 246, Ibrahimia, 21321 Alexandria (Egypt) E-mail:
Department of Chemistry and Molecular Pharmacology, Institute for Research in Biomedicine Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona (Spain) E-mail:
ChemistryOpen. 2012 Jun;1(3):147-52. doi: 10.1002/open.201200012. Epub 2012 Jun 11.
Peptide-bond formation is a pivotal process in the synthesis of peptide oligomers. Among the various coupling methodologies described, carbodiimides combine strong acylation potency and smooth reaction conditions, and they are commonly used in the presence of N-hydroxylamine additives. In recent years, acidic oxime templates, mainly ethyl 2-cyano-2-(hydroxyimino) acetate (Oxyma), have emerged as highly reactive alternatives to the classic and explosive-prone benzotriazolic additives, 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt). However, to achieve certain biochemical targets, less reactive species, such as N-hydroxysuccinimide (HOSu) esters, are often required to obtain stability under aqueous conditions. In the present study, we report on a new family of water-soluble N-alkyl-cyanoacetamido oximes, most of which have proven useful in the construction of active carbonates for the introduction of fluorenylmethoxycarbonyl (Fmoc) with minimal impact of dipeptide impurities. We performed a direct comparison of these new N-alkyl-cyanoacetamido oximes with HOSu in order to evaluate their capacity to retain optical purity and their coupling efficiency in the assembly of bulky residues.
肽键的形成是寡肽合成中的一个关键过程。在描述的各种偶联方法中，碳二亚胺结合了强大的酰化能力和顺畅的反应条件，并且通常在 N-羟基胺添加剂的存在下使用。近年来，酸性肟模板，主要是乙基 2-氰基-2-（羟亚氨基）乙酸酯（Oxyma），已经成为经典的、易爆的苯并三唑添加剂 1-羟基苯并三唑（HOBt）和 1-羟基-7-氮杂苯并三唑（HOAt）的高反应性替代品。然而，为了实现某些生化目标，通常需要使用反应性较低的物质，如 N-羟基琥珀酰亚胺（HOSu）酯，以在水相条件下获得稳定性。在本研究中，我们报告了一系列新的水溶性 N-烷基-氰基乙酰胺肟，其中大多数在构建用于引入芴甲氧羰基（Fmoc）的活性碳酸酯方面非常有用，对二肽杂质的影响最小。我们直接比较了这些新的 N-烷基-氰基乙酰胺肟与 HOSu，以评估它们在保留光学纯度和在组装大体积残基时的偶联效率方面的能力。
