East China University of science and technology has made new progress in enzymatic synthesis of chiral amino alcohols

Recently, Professor Xu Jianhe, Professor of East China University of Science and Technology, and Professor Zheng Gaowei, Professor Nicholas J Turner of University of Manchester, have made new breakthroughs in asymmetric asymmetric synthesis of chiral ortho amino alcohols The research results were published in ACS Catalysis (DOI: 10.1021 / acscan 9b03889) under the title of "energetic synthesis of domestic amino alcools using amine dehydrogenases" Chiral o-aminoalcohols are widely found in bioactive molecules, and they are also a kind of important drug structural blocks, such as the anti tuberculosis drug ethambutol, the anti AIDS drug elvitegravir and so on There are some problems in the chemical synthesis of chiral o-aminoalcohols, such as harsh reaction conditions and low selectivity Amine dehydrogenase can be used as an amino donor to catalyze the direct reduction and amination of carbonyl group to produce corresponding chiral amines, which is considered as a promising green synthesis route of chiral amines However, it has not been reported that it can be used to catalyze the asymmetric reduction and amination of α - hydroxyketone to prepare chiral amino alcohols Through the molecular transformation of wild leucine dehydrogenase, the research team first developed an amine dehydrogenase with amination reducing activity to α - hydroxyketone substrate, realized a series of reduction amination of α - hydroxyketone substrate, and synthesized optically pure (s) - ortho amino alcohol products The enantiomeric excess value EE was more than 99% Finally, the enzymatic synthesis of (s) - 2-amino-1-hexanol and (s) - 2-amino-butanol, the precursor of anti tuberculosis drug ethambutol, was realized by using the developed amine dehydrogenase, which proved the feasibility of catalytic synthesis of chiral amino alcohol In recent years, the team has made a series of research results in the synthesis of chiral amines catalyzed by amine dehydrogenases, such as significantly expanding the range of substrate catalyzed by amine dehydrogenases through molecular transformation (ACS catalyst 2018, 8, 2622 − 2628); using independently developed amine dehydrogenases, the team has designed a new multi enzyme cascade reaction way for efficient synthesis of chiral amines (J org Chem 2019, 84 , 14987; ChemCatChem   2015 , 7 , 3838 ） 。 The above work was completed by Dr Chen Feifei under the guidance of three professors, and supported by NSFC and China Scholarship Fund.