66264-83-3Relevant academic research and scientific papers
Iterative Alanine Scanning Mutagenesis Confers Aromatic Ketone Specificity and Activity of L-Amine Dehydrogenases
Mu, Xiaoqing,Wu, Tao,Mao, Yong,Zhao, Yilei,Xu, Yan,Nie, Yao
, p. 5243 - 5253 (2021/11/16)
Direct reductive amination of prochiral ketones catalyzed by amine dehydrogenases is attractive in the synthesis of active pharmaceutical ingredients. Here, we report the protein engineering of L-Bacillus cereus amine dehydrogenase to allow reactivity on synthetically useful aromatic ketone substrates using an iterative, multiple-site alanine scanning mutagenesis approach. Mutagenesis libraries based on molecular docking, iterative alanine scanning, and double-proximity filter approach significantly expand the scope of active pharmaceutical ingredients relevant building blocks. The eventual quintuple mutant (A115G/T136A/L42A/V296A/V293A) showed reactivity toward aromatic ketones 12 a (5-phenyl-pentan-2-one) and 13 a (6-phenyl-hexan-2-one), which have not been reported to serve as targets of reductive amination by currently available amine dehydrogenases. Docking simulation and tunnel analysis provided valuable insights into the source of the acquired specificity and activity.
Enzymatic asymmetric synthesis of enantiomerically pure aliphatic, aromatic and arylaliphatic amines with (R)-selective amine transaminases
Schaetzle, Sebastian,Steffen-Munsberg, Fabian,Thontowi, Ahmad,Hoehne, Matthias,Robins, Karen,Bornscheuer, Uwe T.
experimental part, p. 2439 - 2445 (2011/11/06)
Seven (R)-selective amine transaminases (R-ATAs) recently discovered by an in silico-based approach in sequence databases were produced recombinantly in Escherichia coli and subjected to partial purification by ammonium sulfate precipitation. A range of additives and various buffers were investigated to identify best conditions to ensure good storage stability and stable activity during biocatalysis. All enzymes show pH optima between pH 7.5-9. These R-ATAs were then applied in the asymmetric synthesis of twelve aliphatic, aromatic and arylaliphatic (R)-amines starting from the corresponding prochiral ketones using a lactate dehydrogenase/glucose dehydrogenase system to shift the equilibrium. For all ketones, at least one enzyme was found that allows complete conversion to the corresponding chiral amine having excellent optical purities >99% ee. Variations in substrate profiles are also discussed based on the phylogenetic relationships between the seven R-ATAs. Thus, we have identified a versatile toolbox of (R)-amine transaminases showing remarkable properties for application in biocatalysis. Copyright
Ir(I)-catalyzed enantioselective secondary sp3 C-H bond activation of 2-(alkylamino)pyridines with alkenes
Pan, Shiguang,Endo, Kohei,Shibata, Takanori
supporting information; experimental part, p. 4692 - 4695 (2011/11/06)
A cationic Ir(I)-tolBINAP complex catalyzed an enantioselective C-C bond formation initiated by secondary sp3 C-H bond cleavage adjacent to a nitrogen atom. The reaction of 2-(alkylamino)pyridines with various alkenes gave chiral amines in good yields with high enantiomeric excesses.
Betuligenol derivative with growth inhibition and antifeedant activity
Chattopadhyay, Sunil K.,Srivastava, Sachin,Sashidhara, Koneni V.,Tripathi, Arun K.,Bhattacharya, Asish K.,Negi, Arvind S.
, p. 1729 - 1731 (2007/10/03)
The title chiral amine, 3-(4-methoxyphenyl)-1-methylpropylamine 5 has been synthesized from naturally abundant betuligenol 1 in three steps and also in good yield. Furthermore, the versatile intermediate 3 could be manipulated for the preparation of chiral disulphide 7. The amine derivative 5 prepared from (-)-betuligenol showed significant growth inhibition and antifeedant activity.
