Yan Xiaosheng, Cao Jinlian, Luo Huan, Li Zhao, Cao Zexing, Mo Yirong, Jiang Yun-Bao
MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.
Nat Commun. 2024 Oct 28;15(1):9271. doi: 10.1038/s41467-024-53744-x.
Enantioselective synthesis governed by chiral catalysts has been extensively developed, but that without any chiral auxiliaries or chiral catalysts is rare, particularly when remote stereogenic centers are involved. Here we report an enantioselectivity of heterochiral coupling in the one-pot reaction of racemic hydrazides with achiral 1,4-bis(isothiocyanine)benzene, yielding preferentially the heterochiral bilateral azapeptides over the homochiral ones. Despite bearing two hydrogen-bonded β-turn structures that allow intramolecular chiral transfer, the bilateral azapeptide products have two chiral centers separated by 14 atoms or 15 bonds, which prevent the direct intramolecular asymmetric communication between the two chiral centers. Interestingly, the heterochiral azapeptides feature intermolecular hydrogen bonding stacking between homochiral β-turns to form a superstructure of alternative M- and P-helices in the crystals. In contrast, the homochiral azapeptide counterparts adopt a β-sheet-like structure, which is less favorable compared to the helical-like superstructure from heterochiral azapeptides, accounting for the favored heterochiral coupling of the one-pot reaction. This work demonstrates enantioselective synthesis involving distant chiral centers through the formation of biomimetic superstructures, opening up new possibilities for the regulation of enantioselectivity.
由手性催化剂控制的对映选择性合成已得到广泛发展，但在没有任何手性助剂或手性催化剂的情况下进行的对映选择性合成却很少见，尤其是当涉及远程立体中心时。在此，我们报道了外消旋酰肼与非手性的1,4 - 双（异硫氰基）苯在一锅反应中的异手性偶联的对映选择性，优先生成异手性双边氮杂肽而非同手性的。尽管双边氮杂肽产物带有两个允许分子内手性转移的氢键β - 转角结构，但两个手性中心被14个原子或15个键隔开，这阻止了两个手性中心之间直接的分子内不对称通讯。有趣的是，异手性氮杂肽在晶体中具有同手性β - 转角之间的分子间氢键堆积，形成交替的M - 螺旋和P - 螺旋的超结构。相比之下，同手性氮杂肽对应物采用β - 折叠状结构，与异手性氮杂肽的螺旋状超结构相比不太有利，这解释了一锅反应中异手性偶联占优的原因。这项工作通过仿生超结构的形成展示了涉及远距离手性中心的对映选择性合成，为对映选择性的调控开辟了新的可能性。
