Wang Yuanyuan, Madsen Anders Ø, Diness Frederik, Meldal Morten
Department of Chemistry, Center for Evolutionary Chemical Biology, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark.
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Chemistry. 2017 Oct 9;23(56):13869-13874. doi: 10.1002/chem.201702900. Epub 2017 Sep 12.
Cascade reactions proceeding through peptide-derived N-carbamoyl iminium ions are reported. Two new reactions of N-carbamoyl iminium ions are described, including a stereoselective double cyclization generating N,N'-aminals and an acid-promoted auto-oxidation. Mechanistic investigations revealed that the N,N'-aminal formation is reversible under strongly acidic conditions. Both of these new reactions proved to be completely orthogonal to subsequent CuAAC chemistry. The reactions were performed in solution and on solid support. The robustness and high stereoselectivity of the methodology holds great promise for applications in parallel diversity-oriented synthesis and in combinatorial synthesis for drug screening.
报道了通过肽衍生的N-氨基甲酰基亚胺离子进行的级联反应。描述了N-氨基甲酰基亚胺离子的两个新反应，包括生成N，N'-缩醛胺的立体选择性双环化反应和酸促进的自氧化反应。机理研究表明，在强酸性条件下，N，N'-缩醛胺的形成是可逆的。这两个新反应均被证明与随后的铜催化的叠氮化物-炔烃环加成（CuAAC）化学完全正交。这些反应在溶液中和在固体载体上进行。该方法的稳健性和高立体选择性在面向平行多样性的合成以及用于药物筛选的组合合成中具有广阔的应用前景。
