Vongvilai Pornrapee, Ramström Olof
KTH-Royal Institute of Technology, Department of Chemistry, Teknikringen 30, S-10044 Stockholm, Sweden.
J Am Chem Soc. 2009 Oct 14;131(40):14419-25. doi: 10.1021/ja9052015.
The Strecker reaction is one of the most important multicomponent reactions developed, leading to alpha-aminonitriles that are versatile substrates for many synthetic applications. In the present study, this reaction type has been applied to a double dynamic covalent resolution protocol, leading to efficient C-C- and C-N-bond generation as well as chiral discrimination. The combination of transimination with imine-cyanation enabled the dynamic exchange in more than one direction around a single stereogenic center of restricted structure. This multiple exchange process could generate a vast range of compounds from a low number of starting materials in very short time. The resulting double dynamic covalent systems, created under thermodynamic control, were subsequently coupled in a one-pot process with kinetically controlled lipase-mediated transacylation. This resulted in complete resolution of the dynamic systems, yielding the optimal N-acyl-alpha-aminonitriles for the enzyme, where the individual chemoenzymatic reactions could produce enantiomerically pure acylated N-substituted alpha-aminonitriles in good yields.
施特雷克反应是已开发的最重要的多组分反应之一，可生成α-氨基腈，而α-氨基腈是许多合成应用中的通用底物。在本研究中，这种反应类型已应用于双动态共价拆分方案，从而实现了高效的C-C键和C-N键生成以及手性识别。转亚胺化与亚胺氰化的结合使得在结构受限的单个立体中心周围能够进行不止一个方向的动态交换。这种多重交换过程可以在极短的时间内从少量起始原料生成大量化合物。在热力学控制下产生的双动态共价体系随后在一锅法中与动力学控制的脂肪酶介导的转酰化反应偶联。这导致动态体系的完全拆分，产生了对该酶而言最优的N-酰基-α-氨基腈，其中各个化学酶促反应能够以良好的产率生成对映体纯的酰化N-取代α-氨基腈。
