Scale up of key drug intermediate, L-2-Aminobutyric acid synthesis by novel multienzyme one pot process
Implementing Organization
Principal Investigator
Dr. Ramalingam Subramanian
Anna University, Chennai, Tamil Nadu (600025)
Project Overview
L-2-Aminobutyric acid (L-2ABA) is a crucial chiral intermediate for the synthesis of anti-epileptic drugs like levetiracetam, brivaracetam, and antituberculotic ethambutol. Its cost in bulk quantities ranges from 17 to 20 per Kg, with a global market demand of over one billion US dollars per annum. The three major utilizers of this intermediate are M/s. Lupin Ltd, Aurobindo pharma Ltd, and Divis Laboratories, Hyderabad. Currently, L-2-ABA is produced by chemical methods, leading to undesirable racemic mixtures and high costs. Fermentation is not preferred by pharma majors in India due to high CAPEX and higher power requirements. A multistep one pot enzymatic process has been developed in China, which is rated as the best among various methods. India is importing this starting material to fulfill its entire requirements, but major bottlenecks include the cost of substrates, less efficient enzymes, and less efficient enzymes. The proposed method aims to synthesize L-2-Aminobutyric acid L-2-ABA using a multistep one pot enzymatic process from citraconate. The process will scale up from 20L to 500L scale, using glucose yeast extract medium and three enzymes. The study focuses on developing an indigenously developed technology for producing L-2-ABA by pharma majors through a preferred enzymatic multistep one pot process. This technology is superior over the prevailing state-of-the-art Chinese enzymatic process due to its cheaper substrate and availability of more efficient enzymes. The technology will partly mitigate India's demand for raw material L-2ABA for making levetiracetam 4000 MT/annum and ethambutol in India.