The asymmetric reduction of 2-benzoylpyridine derivatives for enantiopure alcohols with excellent enantioselectivity and atom economy is still a challenging synthetic problem due to the coordination effects of 2-pyridine and substituents. In this study, we investigated an alternative cost-effective and green route for the enantioselective bioreduction of prochiral 2-benzoylpyridine derivatives employing a novel biocatalyst Cryptococcus sp. whole-cell to corresponding (S)-alcohols. This biocatalyst was more enantioselective toward the reduction of 2-benzoylpyridine derivatives with a para-substituent on the phenyl group, rather than those with an ortho- or meta-substituent. This property was quite contrary to the cases of known chemical catalysts. Moreover, Cryptococcus sp. whole-cell-catalyzed reduction of (4-chlorophenyl)-(pyridin-2-yl) methanone (CPMK) could proceed with perfect enantioselectivity in aqueous hydrophilic ionic liquid (IL) media, affording the product (S)-(4-chlorophenyl)-(pyridin-2-yl)methanol [(S)-CPMA] with excellent enantioselectivity (99% ee) and good conversion (89%), which is a crucial chiral synthon of new antiallergic drug, Betahistine. To overcome the known toxicity of hydrophilic ILs to cells, a high IL-tolerant mutant of Cryptococcus sp. (M9-3) was adopted in the reaction. The excellent tolerance of the biocatalyst to various hydrophilic ILs enabled the exploration of the positive effects of ILs on the biocatalytic efficiency and enantio-selectivity. In addition, the enzymatic hydrolyzate of bagasse was firstly used as the co-substrate during the asymmetric bioreduction of CPMK, with a higher conversion achieved (92%) than using pure glucose. This is a novel and economical route for the green synthesis of chiral diarylmethanols.

由于2-吡啶和取代基的配位作用，具有优异的对映选择性和原子经济性的对映纯醇的2-苯甲酰基吡啶衍生物的不对称还原仍然是一个具有挑战性的合成问题。在这项研究中，我们调查了一种使用新型生物催化剂隐球菌对手性2-苯甲酰基吡啶衍生物进行对映选择性生物还原的替代成本有效和绿色途径。全细胞转化为相应的（S）醇。这种生物催化剂对还原具有苯基上的对位取代基的2-苯甲酰基吡啶衍生物，而不是具有邻位或间位的衍生物，具有更强的对映选择性。-取代基。该性质与已知化学催化剂的情况完全相反。此外，隐球菌属。（4-氯苯基）-（吡啶-2-基）甲酮（CPMK）的全细胞催化还原可在亲水性离子液体（IL）介质中以完美的对映选择性进行，得到产物（S）-（4-氯苯基） ）-（吡啶-2-基）甲醇[（S）-CPMA]具有出色的对映选择性（99％ee）和良好的转化率（89％），这是新的抗过敏药Betahistine的关键手性合成子。为了克服亲水性IL对细胞的已知毒性，隐球菌的高IL耐受突变体sp。反应中采用（M9-3）。生物催化剂对各种亲水性IL的优异耐受性使得能够探索IL对生物催化效率和对映选择性的积极作用。此外，在CPMK的不对称生物还原过程中，首先将甘蔗渣的酶水解物用作共底物，与使用纯葡萄糖相比，具有更高的转化率（92％）。这是绿色合成手性二芳基甲醇的新颖且经济的途径。