ENZYMATIC RESOLUTION OF ANTIDEPRESSANT DRUG PRECURSORS IN AN UNDERGRADUATE LABORATORY

• Published in: Química Nova
• Main Authors: Luís M. R. Solano, Nuno M. T. Lourenço
• Format: Article in Journal/Newspaper
• Language: English; Spanish; Portuguese
• Published: Sociedade Brasileira de Química 2015
• Subjects: sec-alcohols; esters; lípase; enantiomers; resolution; Chemistry; QD1-999; Antarc*; Antarctica
• Online Access: https://doi.org/10.5935/0100-4042.20140306; https://doaj.org/article/7a016c00f3a84b25b8fd0256f8675c7c

The use of biocatalysts in synthetic chemistry is a conventional methodology for preparing enantiomerically enriched compounds. Despite this fact, the number of experiments in chemical teaching laboratories that demonstrate the potential of enzymes in synthetic organic chemistry is limited. We describe a laboratory experiment in which students synthesized a chiral secondary alcohol that can be used in the preparation of antidepressant drugs. This experiment was conducted by individual students as part of a Drug Synthesis course held at the Pharmacy Faculty, Lisbon University. This laboratory experiment requires six laboratory periods, each lasting four hours. During the first four laboratory periods, students synthesized and characterized a racemic ester using nuclear magnetic resonance spectroscopy and gas chromatography. During the last two laboratory periods, they performed enzymatic hydrolysis resolution of the racemic ester using Candida antarctica lipase B to yield enantiomerically enriched secondary alcohol. Students successfully prepared the racemic ester with a 70%-81% overall yield in three steps. The enzymatic hydrolysis afforded (R)- secondary alcohol with good enantioselectivity (90%-95%) and reasonable yields (10%-19%). In these experiments, students were exposed to theoretical and practical concepts of aromatic acylation, ketone reduction, esterification, and enzymatic hydrolysis.