Deciphering molecular interaction of binaphthyl compounds with Penicillium expansum lipase: enantioselectivity and reactivity prediction for lipase
Yan Liu, Longguang Jiang, Ling Song, Datao Tu, Wei Zheng, Ping Huang, Mingmao Chen, Xueyuan Chen
文献索引：10.1039/C7ME00120G
全文：HTML全文
摘要
The determination of the dominant factor for the enantioselectivity and reactivity of lipase-catalyzed reactions of binaphthyl compounds is of wide concern. To understand the stereo-dependent behavior of 2,2-binaphthyl compounds towards lipase, we established a platform for effectively evaluating the reactivity and enantioselectivity of lipase towards binaphthyl compounds by investigating the binding interactions between substrate and lipase. Penicillium expansum lipase (PEL) and three 2-amino-2′-hydroxy-1,1′-binaphthyl compounds (NBs) with different linker lengths were selected as the model lipase and substrates, respectively, in this study. The key interaction parameters such as binding affinities, binding modes, and thermodynamic parameters between NBs and PEL were determined for the first time, and the results revealed that the substrate–lipase binding interaction is a prerequisite for successful lipase-catalyzed reaction. The effect of binding discrepancies of NBs with different alkyl chain lengths on lipase reactivity and enantioselectivity was also unveiled. From the analytical results of NB–PEL binding interactions, a PEL-catalyzed two-step resolution strategy was further established and optimized for the gram-scale synthesis of optically pure NB. The investigation on the molecular interaction between NBs and PEL showed great promise for rationally guiding the synthesis of binaphthyl derivatives that are suitable for efficient optical resolution by the commercially available lipase.