A Viedma ripening route to an enantiopure building block for Levetiracetam and Brivaracetam

2019 ◽  
Vol 17 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Iaroslav Baglai ◽  
Michel Leeman ◽  
Richard M. Kellogg ◽  
Willem L. Noorduin
Keyword(s):  
Building Block ◽  
Rational Design ◽  
Large Scale ◽  
Enantiomerically Pure ◽  
Ripening Process ◽  
Simple Route ◽  
Chiral Component ◽  
Design And Application

A simple route to enantiomerically pure (S)-2-aminobutyramide – the chiral component of the anti-epileptic drugs Levetiracetam and Brivaracetam has been developed. This approach is based on the rational design and application of a Viedma ripening process. The practical potential of the process is demonstrated on a large scale.

Enantiomerically Pure Isophorone Diamine [3-(Aminomethyl)-3,5,5-trimethylcyclohexylamine]:  A Chiral 1,4-Diamine Building Block Made Available on Large Scale

2006 ◽  
Vol 71 (25) ◽  
pp. 9312-9318 ◽  
Author(s):  
Albrecht Berkessel ◽  
Katrin Roland ◽  
Michael Schröder ◽  
Jörg M. Neudörfl ◽  
Johann Lex
Keyword(s):  
Building Block ◽  
Large Scale ◽  
Enantiomerically Pure

scholarly journals (R)-α-Aminoadipic Acid: A Versatile Precursor for the Synthesis of D-Amino Acids

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Amina Sadiq ◽  
Norbert Sewald
Keyword(s):  
Amino Acids ◽  
Building Block ◽  
Large Scale ◽  
Starting Material ◽  
Pipecolic Acid ◽  
Cephalosporin C ◽  
Enzymatic Cleavage ◽  
Enantiomerically Pure ◽  
Unusual Amino Acids ◽  
Derivatives Of

The ready accessibility of (R)-α-aminoadipic acid by enzymatic cleavage of cephalosporin C (CephC) in the production of 7-aminocephalosporanic acid (7-ACA) on a large scale makes it a favorable chiral pool building block for the synthesis of unusual amino acids. A route for the synthesis of C-5-alkenyl and C-6-alkylidene derivatives of (R)-pipecolic acid is described which utilizes (R)-α-aminoadipic acid as the enantiomerically pure starting material. Moreover, the synthesis of azido and triazolyl derivatives of (R)-α-aminoadipic acid is reported.

scholarly journals Enantiomerically Pure [2.2]Paracyclophane-4-thiol: A Planar Chiral Sulfur-Based Building Block Readily Available by Resolution with an Amino Acid Chiral Auxiliary

2016 ◽  
Vol 81 (9) ◽  
pp. 3961-3966 ◽  
Author(s):  
Adrien Vincent ◽  
Damien Deschamps ◽  
Thomas Martzel ◽  
Jean-François Lohier ◽  
Christopher J. Richards ◽  
...  
Keyword(s):  
Amino Acid ◽  
Building Block ◽  
Chiral Auxiliary ◽  
Enantiomerically Pure

scholarly journals Efficient Synthesis of Rare Disaccharides by Engineered β-Glucosidase Based on Hydropathy Index

2020 ◽  
Author(s):  
Kangle Niu ◽  
Zhengyao Liu ◽  
Yuhui Feng ◽  
Tianlong Gao ◽  
Zhenzhen Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Rational Design ◽  
Large Scale ◽  
Catalytic Site ◽  
Scale Production ◽  
Total Production ◽  
Amino Acid Residues ◽  
Hydropathy Index ◽  
Reverse Hydrolysis ◽  
Hydrolysis Activity

<p>Oligosaccharides have important therapeutic applications. A useful route for oligosaccharides synthesis, especially rare disaccharides, is reverse hydrolysis by <i>β</i>-glucosidase. However, the low conversion efficiency of disaccharides from monosaccharides limits its large-scale production because the equilibrium is biased in the direction of hydrolysis. Based on the analysis of the docking results, we hypothesized that the hydropathy index of key amino acid residues in the catalytic site is closely related with disaccharide synthesis and more hydrophilic residues located in the catalytic site would enhance reverse hydrolysis activity. In this study, positive variants<i> Tr</i>Cel1b<sup>I177S</sup>, <i>Tr</i>Cel1b<sup>I177S/I174S</sup>, and <i>Tr</i>Cel1b<sup>I177S/I174S/W173H</sup>, and one negative variant <i>Tr</i>Cel1b<sup>N240I</sup> were designed according to the <u>H</u>ydropathy <u>I</u>ndex <u>F</u>or <u>E</u>nzyme <u>A</u>ctivity (HIFEA) strategy. The reverse hydrolysis with <i>Tr</i>Cel1b<sup>I177S/I174S/W173H </sup>was accelerated and then the maximum total production (<a>195.8 mg/ml/mg enzyme</a>) of the synthesized disaccharides was increased 3.5-fold compared to that of wildtype. On the contrary, <a><i>Tr</i>Cel1b</a><sup>N240I</sup> lost reverse hydrolysis activity. The results demonstrate that<a> </a><a>the average hydropathy index</a> of <a>the key amino acid residues </a>in the catalytic site of<i> Tr</i>Cel1b is an important factor for the synthesis of laminaribiose, sophorose, and cellobiose. The HIFEA strategy provides a new perspective for the rational design of <i>β</i>-glucosidases used for the synthesis of oligosaccharides.</p>

ChemInform Abstract: A Large-Scale Synthesis of Enantiomerically Pure γ-Hydroxyorganochalcogenides.

ChemInform ◽  
2010 ◽  
Vol 41 (23) ◽  
pp. no-no
Author(s):  
Jefferson L. Princival ◽  
Morilo S. C. de Oliveira ◽  
Alcindo A. Dos Santos ◽  
Joao V. Comasseto
Keyword(s):  
Large Scale ◽  
Enantiomerically Pure ◽  
Large Scale Synthesis

ChemInform Abstract: A Large-Scale Synthesis of Enantiomerically Pure Cetirizine Dihydrochloride Using Preparative Chiral HPLC.

ChemInform ◽  
2010 ◽  
Vol 32 (33) ◽  
pp. no-no
Author(s):  
Derek A. Pflum ◽  
H. Scott Wilkinson ◽  
Gerald J. Tanoury ◽  
Donald W. Kessler ◽  
Hali B. Kraus ◽  
...  
Keyword(s):  
Large Scale ◽  
Chiral Hplc ◽  
Enantiomerically Pure ◽  
Large Scale Synthesis
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