Laboratory of Medicinal Chemistry, Faculty of Pharmacy and Institute of, Biomedicine (IBUB), University of Barcelona, Barcelona Science Park, Baldiri Reixac 10-12, Barcelona, 08028, Spain.
CIBER-BBN, Networking Centre for Bioengineering, Biomaterials & Nanomedicine, Baldiri Reixac 10-12, Barcelona, 08028, Spain.
Chemistry. 2018 Sep 25;24(54):14513-14521. doi: 10.1002/chem.201802877. Epub 2018 Aug 28.
Multiple multicomponent reactions rapidly assemble complex structures. Despite being very productive, the lack of selectivity and the reduced number of viable transformations restrict their general application in synthesis. Hereby, we describe a rationale for a selective version of these processes based in the preferential generation of intermediates which are less reactive than the initial substrates. In this way, applying the Groebke-Blackburn-Bienaymé reaction on a range of α-polyamino-polyazines, we prepared a family compact heterocyclic scaffolds with relevant applications in medicinal and biological chemistry (live cell imaging probes, selective binders for DNA quadruplexes, and antiviral agents against human adenoviruses). The approach has general character and yields complex molecular targets in a selective, tunable and direct manner.
多种多组分反应能够快速组装复杂结构。尽管这种方法具有很高的产率，但选择性不足和可行转化的数量减少限制了它们在合成中的广泛应用。在此，我们描述了一种基于优先生成比初始底物反应性更低的中间体的选择性版本的这些反应的原理。通过在一系列α-聚氨基-聚嗪上应用 Groebke-Blackburn-Bienaymé 反应，我们制备了一系列紧凑的杂环支架，这些支架在医学和生物化学中有重要的应用（活细胞成像探针、DNA 四链体的选择性结合物和抗人类腺病毒的抗病毒剂）。该方法具有通用性，能够以选择性、可调性和直接性的方式得到复杂的分子靶标。
