An Efficient and Novel Synthesis of Pregabalin with Enantioselective Enzymatic Hydrolysis using CAL-B Enzyme

• Published in: Asian Journal of Research in Chemistry 2019-03, Vol.12 (2), p.55-57
• Main Authors: Gokavarapu, Kishore, Devkar, Rahul Uttamrao, Gokavarapu, Sarita, Samala, Shiva Rama Krishna, Rao, Durga Prasad
• Format: Article
• Language: English
• Subjects: Acids; Ammonia; Catalytic converters; Coordination compounds; Enantiomers; Enzymes; Esterification; Hydrolysis; Lipase; Organic chemistry; Pictures; Potassium; Potassium hydroxides; Racemization; Substrates; Synthesis
• ISSN: 0974-4169; 0974-4150
• DOI: 10.5958/0974-4150.2019.00012.9

To overcome this limitation, racemization of the unreacted isomer with a strong base or a metal complex is a possible alternative.3 Desmmetrization is another way to produce an optically pure reaction product with a 100% theoretical yield in the absence of a racemizer.4 various chemical and enzymatic methods have been reported for desmmetrization to yield optically pure products. Many structurally diverse organic molecules have been utilized as lipase substrates for reactions, including hydrolysis, esterification and ammoniolysis, some of which provide quite clear pictures of the binding mode near the active site residues combined with their crystalline structures. The enzymatic route of synthesis of S-Pregabalin key starting material is Isovelardehyde, reacted with cyanoacetamide in the presence of potassium hydroxide water as medium followed by acidic hydrolysis gave the diacid (CMMHA), obtained diacid converted as diester in the presence of methanol under catalytic acidic condition, diester converted as monoester in the presence of CAL-B enzyme as R isomer with 95.5% of optical purity which was converted as amide in the presence of Aqueous ammonia and finally with Hoffman reaction gave the desired isomer of S-Pregabalin.