Engineering the simply asymmetric Morita–Baylis–Hillman reactions in a sodium phosphate buffer system: from enzyme‐ to proline‐catalyzed transformation

Abstract

BACKGROUND The Morita–Baylis–Hillman (MBH) reaction is an important carbon–carbon bond‐forming reaction. However, most MBH reactions suffer disadvantages such as high amounts of catalyst and hazardous solvents, long reaction time, low reactivity and selectivity. In this study, simple, cost‐effective and eco‐friendly asymmetric MBH reactions are developed. RESULTS Following our previous study that the commercial Candida antarctica lipase B (lipase CalB)‐catalyzed MBH reaction can be activated by introducing an amide compound as a co‐catalyst, the recombinant lipase CalBs (rCalBs) with polyamino acid tails are first attempted to be used in the same MBH reaction, but unfortunately chiral MBH products are not obtained. Enoate reductase (ER) is found to give asymmetric transformation of the MBH reaction with a conversion of 36.9% and enantiomeric excess (e.e.p) of 6.8% when other enzyme resources are expanded. According to the observation that the surface amino acids of ER may be key factors in achieving the MBH reaction, single amino acids are subsequently selected to catalyze the MBH reactions, and the reverse configuration of (R)‐ and (S)‐MBH products with e.e.p of 63.9% and 62.1% for single l‐proline‐ and d‐proline‐catalyzed MBH reactions are reached only in 4 h, respectively. CONCLUSION Proline can afford the asymmetric MBH reaction in a sodium phosphate buffer only in 4 h without the help of the other co‐catalyst in our study, which is superior to those reported. The study aims to introduce a novel phenomenon observed from enzyme‐catalyzed to proline‐catalyzed MBH reactions. © 2022 Society of Chemical Industry (SCI).

Unlocking the function promiscuity of old yellow enzyme to catalyze asymmetric Morita-Baylis-Hillman reaction

“…The step 1: Michael addition. HPO 4 2- as a nucleophile attacks substrate 1 59 . The step 2: Aldol reaction.…”