23239-32-9Relevant articles and documents
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.
ASPARAGINE DERIVATIVES AND METHODS OF USE THEREOF
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, (2021/12/31)
The present invention relates to compounds of formulas (A) and (I), pharmaceutically acceptable salts thereof, and solvates of any of them, pharmaceutical compositions comprising them, methods of preparation thereof, intermediate compounds useful for the preparation thereof, and methods of treatment or prophylaxis of diseases, in particular cancer, such as colorectal cancer, using these. (A) (I)
The Synthesis of Primary Amines through Reductive Amination Employing an Iron Catalyst
B?umler, Christoph,Bauer, Christof,Kempe, Rhett
, p. 3110 - 3114 (2020/06/01)
The reductive amination of ketones and aldehydes by ammonia is a highly attractive method for the synthesis of primary amines. The use of catalysts, especially reusable catalysts, based on earth-abundant metals is similarly appealing. Here, the iron-catalyzed synthesis of primary amines through reductive amination was realized. A broad scope and a very good tolerance of functional groups were observed. Ketones, including purely aliphatic ones, aryl–alkyl, dialkyl, and heterocyclic, as well as aldehydes could be converted smoothly into their corresponding primary amines. In addition, the amination of pharmaceuticals, bioactive compounds, and natural products was demonstrated. Many functional groups, such as hydroxy, methoxy, dioxol, sulfonyl, and boronate ester substituents, were tolerated. The catalyst is easy to handle, selective, and reusable and ammonia dissolved in water could be employed as the nitrogen source. The key is the use of a specific Fe complex for the catalyst synthesis and an N-doped SiC material as catalyst support.
