Chemoenzymatic synthesis of levetiracetam and analogues

• Grant number: 13/16636-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2013
• End date: February 28, 2015
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Cintia Duarte de Freitas Milagre
• Grantee: Bruno Sérgio Do Amaral
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Biocatalysts (enzymes and / or microorganisms) are widely used to create or resolve chiral centers, especially for drug synthesis. Levetiracetam (LEV), commercially known as Keppra®, is a chiral substance with anticonvulsant properties whose pharmacological activity is related to its (S) enantiomer. The increase of LEV usage over other anticonvulsant drugs is closely associated with its low occurrence of side effects. Several routes for LEV chemosynthetic production are reported in the literature. Most of them involve numerous synthetic steps, high-energy consumption, use of metal catalysts and low overall yields. On the other hand, this project aims to develop a chemoenzymatic route, with fewer steps, milder conditions and environmentally friendly reaction for the synthesis of LEV and analogues. The first step will focus on the synthesis of butanecyanohydrin from cyanosilylation of propanal, followed by the formation of halogenated compound. Different nitrogen heterocycles will replace the halogen atom to produce the starting materials for microbial enzymatic reactions. The main strategies to obtain the desired products, with high yields and enantioselectivity, will be the enzymatic selection and screening and use of ionic liquids as reaction medium.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AMARAL, Bruno Sérgio Do. Síntese quimioenzimática do levetiracetam e análogos. 2015. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara Araraquara.