Lehrstuhl für Organische Chemie I, Ruhr-Universität Bochum, Universitätsstrasse 150, Bochum 44801, Germany.
J Org Chem. 2021 Nov 5;86(21):14964-14973. doi: 10.1021/acs.joc.1c01695. Epub 2021 Oct 11.
The key feature of non-enzymatic self-replicating systems is the formation of catalytically active ternary complexes in which product templates direct precursors into spatial proximity to allow the formation of new covalent bonds. It is possible to create new replicating species by simply evaluating the ternary active complex of an existing replicating system and applying proper isosteric replacements. In this study, we have evaluated the formerly reported self-replicating Diels-Alder reaction having 61 and 33% selectivity for two diastereomeric replicators. An isosteric replacement on the spacer part connecting recognition and reactive sites of the maleimide component was applied by considering the symmetry of catalytically active ternary complexes, and it was shown that self-replication was conserved. Analysis of the new system showed 77 and 21% diastereoselectivity for the two new replicating species. Seeding experiments indicated autocatalytic activity of both replicators. In other words, both replicators compete with each other by catalyzing their own formation from the same reagent source. Another modification was applied by aiming selective blocking of the autocatalytic cycle of the competing diastereomer. The new system showed a diastereoselectivity of about 94% for the favored replicator. The kinetic data of both systems were analyzed by modeling with SimFit simulations.
非酶自复制系统的关键特征是形成催化活性的三元配合物，其中产物模板将前体引导到空间接近，从而允许新的共价键形成。通过简单地评估现有复制系统的三元活性配合物并应用适当的等排替换，就有可能创造新的复制物种。在这项研究中，我们评估了以前报道的具有 61%和 33%两种非对映选择性的自复制 Diels-Alder 反应。通过考虑催化活性三元配合物的对称性，对连接识别和反应性位点的马来酰亚胺部分的间隔部分进行了等排替换，结果表明自复制得以保留。对新系统的分析表明，两种新复制体的非对映选择性分别为 77%和 21%。种晶实验表明两种复制体均具有自动催化活性。换句话说，两种复制体通过催化来自同一试剂源的自身形成来相互竞争。另一种修饰是通过选择性阻断竞争非对映异构体的自动催化循环来实现的。新系统对优势复制体的非对映选择性约为 94%。通过 SimFit 模拟对两个系统的动力学数据进行了分析。
