95310-87-5Relevant academic research and scientific papers
Enantioselective hydrolysis of diethyl 3-hydroxyglutarate to ethyl (S)-3-hydroxyglutarate by immobilized Candida antarctica lipase B
Dong, Hua-Ping,Wang, Ya-Jun,Zheng, Yu-Guo
, p. 90 - 94 (2010)
Optically pure ethyl (S)-3-hydroxyglutarate [(S)-3-EHG] is used as a key precursor for synthesis of a variety of pharmaceutically important compounds. In this work, we established an efficient procedure for enantioselectively hydrolyzing diethyl 3-hydroxyglutarate (3-DHG) to optically active (S)-3-EHG employing immobilized Candida antarctica lipase B (Novozym 435). Under the optimized conditions: pH 7.0, agitation speed 200 rpm, temperature 40 °C, 3-DHG concentration 0.15 mol L-1, and enzyme loading 7 g L -1, (S)-3-EHG was prepared in above 95% ee value and 98.5% yield, and the reaction was free from external mass transfer and intra-particle diffusion limitations and kinetically controlled. The inhibitions of substrate (3-DHG) and product (3-EHG) were excluded because both displayed no decline in activity at elevated concentrations within the given ranges. In addition, ethanol, a byproduct of the reaction, inhibited lipase B following an uncompetitive inhibition pattern. The kinetic constants were obtained through non-linear regression, with values of Vmax 1.29 mmol min-1 g -1, Km 0.06 mol L-1, and Ki 0.37 mol L-1, respectively.
Integrated Biocatalysis in Multistep Drug Synthesis without Intermediate Isolation: A de Novo Approach toward a Rosuvastatin Key Building Block
Metzner, Richard,Hummel, Werner,Wetterich, Frank,K?nig, Burghard,Gr?ger, Harald
supporting information, p. 635 - 638 (2015/06/30)
In this contribution, we report the chemoenzymatic preparation of a key building block for the active pharmaceutical ingredient rosuvastatin, one of the "top 5 blockbuster drugs" with a worldwide market value of 6.25 billion USD in 2012, via a seven-step synthesis without isolation of intermediates and with incorporation of two highly efficient biotransformations. This chemoenzymatic process reaches excellent space-time yields by using high substrate concentrations (several hundred grams per liter), emphasizing the potential of biocatalysis for industrial processes related to pharmaceutical drug synthesis and the compatibility of enzyme chemistry with classical organic synthesis.
A chemoenzymatic approach to the stereocontrolled synthesis of the C1-C11 fragment of (+)-peloruside A
Schoenherr, Heike,Mollitor, Jan,Schneider, Christoph
experimental part, p. 3908 - 3918 (2010/09/05)
A highly efficient and diastereoselective synthesis of the C1C11 fragment of the marine natural product (+)-peloruside A has been developed. Through enzymatic desymmetrization of diethyl 3-hydroxyglutarate with lipase B from Candida antarctica a large-sca
A Practical Synthesis of (R) and (S) 3-Hydroxyglutaric Acid Monoesters by Enzymatic Hydrolysis with a Bacterial Esterase
Monteiro, Julieta,Braun, Jacques,Goffic, Francois Le
, p. 315 - 319 (2007/10/02)
The hemihydrolysis of diethyl-3-hydroxyglutarate with an industrial enzyme, "Esterase 30 000", in a biphasic system allows an efficient enantioselective synthesis of (R) and (S) 3-hydroxyglutaric acid ethyl and t-butyl monoesters in large scale and with excellent yield.
Bifunctional chiral synthons via biochemical methods. 5. Preparation of (S)-ethyl hydrogen-3-hydroxyglutarate, key intermediate to (R)-4-amino-3-hydroxybutyric acid and L-carnitine
Gopalan,Sih
, p. 5235 - 5238 (2007/10/02)
Microbial enantioselective hydrolysis of diethyl-3-hydroxyglutarate afforded (S)-ethyl hydrogen-3-hydroxyglutarate, which was transformed into (R)-4-amino-3-hydroxybutyric acid and L-carnitine, via a Curtius and Hunsdiecker rearrangement, respectively.
