Torres Susana Y, Brieva Rosario, Rebolledo Francisca
Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, 33006-Oviedo, Asturias, Spain.
Org Biomol Chem. 2017 Jun 21;15(24):5171-5181. doi: 10.1039/c7ob01066d.
A chemoenzymatic approach for the synthesis of optically active 4-(3-acetoxyphenyl)-5-(alkoxycarbonyl)-6-methyl-3,4-dihydropyridin-2-ones (3,4-DHP-2-ones) and their hydroxyphenyl derivatives has been developed, the key step being a Candida rugosa lipase (CRL)-catalyzed hydrolysis reaction. As a result, different optically active 3,4-DHP-2-ones have been prepared with very high enantiomeric excesses (ee = 94-99%) and good yields. The enantioenriched 3,4-DHP-2-ones have easily been converted into highly functionalized (R)- and (S)-1,4-dihydropyridines (1,4-DHPs) by means of a Vilsmeier-Haack reaction. Finally, the coupling of the 1,4-DHPs with benzene-1,2-diamine using TFA as an acid promoter provided us the corresponding optically active hybrid 1,5-benzodiazepine-1,4-dihydropyridine (BZD-DHP) derivatives. No racemization took place in these processes and all optically active compounds were obtained in excellent yields.
已开发出一种化学酶法来合成光学活性的4-(3-乙酰氧基苯基)-5-(烷氧羰基)-6-甲基-3,4-二氢吡啶-2-酮（3,4-DHP-2-酮）及其羟基苯基衍生物，关键步骤是皱褶假丝酵母脂肪酶（CRL）催化的水解反应。结果，制备了不同的光学活性3,4-DHP-2-酮，其对映体过量率非常高（ee = 94-99%）且产率良好。通过Vilsmeier-Haack反应，对映体富集的3,4-DHP-2-酮已很容易地转化为高度官能化的（R）-和（S）-1,4-二氢吡啶（1,4-DHP）。最后，以三氟乙酸作为酸促进剂，1,4-DHP与苯-1,2-二胺偶联，为我们提供了相应的光学活性杂化1,5-苯并二氮杂卓-1,4-二氢吡啶（BZD-DHP）衍生物。在这些过程中没有发生消旋化，并且所有光学活性化合物均以优异的产率获得。
