134003-04-6Relevant articles and documents
Efficient synthesis of the intermediate of abacavir and carbovir using a novel (+)-γ-lactamase as a catalyst
Gao, Shuaihua,Zhu, Shaozhou,Huang, Rong,Lu, Yingxiu,Zheng, Guojun
, p. 3878 - 3881 (2015)
Abstract The enantiomers of 2-azabicyclo[2.2.1]hept-5-en-3-one (γ-lactam) are key chiral synthons in the synthesis of antiviral drugs such as carbovir and abacavir. (+)-γ-Lactamase can be used as a catalyst in the enzymatic preparation of optically pure (-)-γ-lactam. Here, a (+)-γ-lactamase discovered from Bradyrhizobium japonicum USDA 6 by sequence-structure guided genome mining was cloned, purified and characterized. The enzyme possesses a significant catalytic activity towards γ-lactam. The active site of the (+)-γ-lactamase was studied by homologous modeling and molecular docking, and the accuracy of the prediction was confirmed by site-specific mutagenesis. The (+)-γ-lactamase reveals the great practical potential as an enzymatic method for the efficient production of carbocyclic nucleosides of pharmaceutical interest.
Novel screening methods - The key to cloning commercially successful biocatalysts
Taylor, Stephen J. C.,Brown, Rob C.,Keene, Phil A.,Taylor, Ian N.
, p. 2163 - 2168 (1999)
Providing sufficient biocatalyst to support the demands of multi tonne product supply can be problematical. Here we describe how screening for and cloning a γ-lactamase overcame biocatalyst supply issues, and greatly improved the actual biocatalytic process. The isolation of an expressing γ- lactamase clone from a gene library necessitated a combination of classical molecular biology techniques together with innovative screening methods to identify a functional clone. Once isolated the enzyme was characterised with regard to its process performance and proved to be active at 500 g L-1 substrate. Further development of the recombinant fermentation and downstream processing has resulted in the ability to produce sufficient biocatalyst from one 500 l fermentation to resolve 5 metric tonnes of (±)-lactam, whilst simplifying the process chemistry greatly.
Stereo- and regiocontrolled synthesis of highly functionalized cyclopentanes with multiple chiral centers
Nonn, Melinda,Binder, Adrienn,Volk, Balázs,Kiss, Loránd
, p. 1199 - 1209 (2020/03/17)
The synthesis of some highly substituted three-dimensional cyclopentanes with multiple chiral centers and with high regiochemical and stereochemical diversity has been accomplished starting from cyclopentadiene-derived aminocyclopentenecarboxylic acids. The small-molecular design consisted of stereo- and regiocontrolled functionalization of the starting cyclopentene β- and γ-amino acids through oxirane formation/oxirane opening and afforded regio- and diastereoisomers of orthogonally protected aminocyclopentanecarboxylates.
Method for synthesizing (1R,4S)-1-amino-4-hydroxymethyl-2-cyclopentene hydrochloride
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Paragraph 0017; 0018, (2017/07/23)
The invention relates to a method for synthesizing (1R,4S)-1-amino-4-hydroxymethyl-2-cyclopentene hydrochloride. According to the method, the reaction conditions are mild, (1S,4R)-(-)-2-azabicyalo[2,2,1]hepta-5-alkene-3-ketone is directly used, (1R,4S)-1-amino-4-hydroxymethyl-2-cyclopentene hydrochloride is obtained through the reactions of hydrolysis and reducing, the yield is high, and the optical purity is high.
