School of Pharmacy, Lanzhou University, 730000, Lanzhou, China.
Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, 730000, Lanzhou, China.
Nat Commun. 2023 Jun 6;14(1):3295. doi: 10.1038/s41467-023-38871-1.
Alkylnitriles play important roles in many fields because of their unique electronic properties and structural characteristics. Incorporating cyanoalkyl with characteristic spectroscopy and reactivity properties into amino acids and peptides is of special interest for potential imaging and therapeutic purposes. Here, we report a copper-catalyzed asymmetric cyanoalkylation of C(sp)-H. In the reactions, glycine derivatives can effectively couple with various cycloalkanone oxime esters with high enantioselectivities, and the reaction can be applied to the late-stage modification of peptides with good yields and excellent stereoselectivities, which is useful for modern peptide synthesis and drug discovery. The mechanistic studies show that the in situ formed copper complex by the coordination of glycine derivatives and chiral phosphine Cu catalyst can not only mediate the single electronic reduction of cycloalkanone oxime ester but also control the stereoselectivity of the cyanoalkylation reaction.
烷基腈由于其独特的电子性质和结构特点，在许多领域都发挥着重要作用。将具有特征光谱和反应性的氰烷基与氨基酸和肽结合，对于潜在的成像和治疗目的具有特殊的意义。在这里，我们报告了铜催化的 C(sp)-H 的不对称氰烷基化反应。在反应中，甘氨酸衍生物可以有效地与各种环烷酮肟酯偶联，具有高对映选择性，并且反应可以应用于具有良好收率和优异立体选择性的肽的后期修饰，这对于现代肽合成和药物发现很有用。机理研究表明，甘氨酸衍生物和手性膦铜催化剂的配位形成的原位铜配合物不仅可以介导环烷酮肟酯的单电子还原，而且可以控制氰烷基化反应的立体选择性。
