Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany.
Warshel Institute for Computational Biology, School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, Shenzhen, China.
Nature. 2022 May;605(7908):84-89. doi: 10.1038/s41586-022-04531-5. Epub 2022 May 4.
Enzymatic stereoselectivity has typically been unrivalled by most chemical catalysts, especially in the conversion of small substrates. According to the 'lock-and-key theory', enzymes have confined active sites to accommodate their specific reacting substrates, a feature that is typically absent from chemical catalysts. An interesting case in this context is the formation of cyanohydrins from ketones and HCN, as this reaction can be catalysed by various classes of catalysts, including biological, inorganic and organic ones. We now report the development of broadly applicable confined organocatalysts for the highly enantioselective cyanosilylation of aromatic and aliphatic ketones, including the challenging 2-butanone. The selectivity (98:2 enantiomeric ratio (e.r.)) obtained towards its pharmaceutically relevant product is unmatched by any other catalyst class, including engineered biocatalysts. Our results indicate that confined chemical catalysts can be designed that are as selective as enzymes in converting small, unbiased substrates, while still providing a broad scope.
酶的立体选择性通常优于大多数化学催化剂，尤其是在小分子底物的转化中。根据“锁钥理论”，酶具有限制的活性位点来容纳其特定的反应底物，这一特性通常在化学催化剂中不存在。在这方面一个有趣的例子是从酮和 HCN 形成氰醇，因为该反应可以被各种类型的催化剂催化，包括生物、无机和有机催化剂。我们现在报告了广泛适用的受限有机催化剂的开发，用于芳香族和脂肪族酮的高度对映选择性氰硅烷基化，包括具有挑战性的 2-丁酮。其具有药物相关产品的选择性（98:2 对映体比率 (e.r.))是任何其他催化剂类别（包括工程化的生物催化剂）都无法比拟的。我们的结果表明，可以设计出与酶一样选择性的受限化学催化剂，用于转化小的、无偏见的底物，同时仍提供广泛的适用范围。
