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Insomnia is a common sleep disorder with a high incidence in the population.
Suvoresen is a new class of hypnotic drugs approved by the U.S. FDA in 2014 to treat the first appetite-restricting agent for difficulty falling asleep or maintaining sleep.
, the efficient synthesis of The Handy 1,4-Nitrous Zodiac Ring, a key structural unit of Suvoreson, is still challenging.
The bio-catalytic and green chemical team led by Zhu Dunming and Wu Qiqing, researchers at the Tianjin Institute of Industrial Biotechnology of the Chinese Academy of Sciences, followed by the use of subamine reductase to catalytic asymmetric reduction alpha, beta-unsaturated subamide synthesis of morphine key intermediates (Adv. Synth. Catal. 2019, 361, 556-561), the asymmetric reductide in the catalytic molecules of the subamine reductase is achieved to build hand 1,4-nitrous zodiazepines.
the study, by screening the subamine reductase library, found that the two enzymes showed complementary stereoscopic selectivity, (R) - or (S) - configuration products of the anti-reflection excess value of more than 99%.
To transform the (R)-selective mamine reductase that produces Suvore's intermediates, obtain mutants with a 61-fold increase in catalytic efficiency, and synthesize a series of handy 1,4-nitrous trophic compounds with different structural characteristics using two enzymes with three-dimensional selectivity complement each other, providing a new structural module for the development of new drugs.
the study revealed the key factors of the catalytic vitality of mutant enzymes through density function calculation and molecular dynamics calculation, and expanded the idea of enzyme transformation.
research has been supported by national key research and development projects, relevant projects of the Chinese Academy of Sciences and Tianjin Science and Technology Program.
research results were recently published in ACS Catalysis, with Xu Zefei, a doctoral student at Tianjin Institute of Technology, and Yao Peiyuan, an associate researcher, as co-authors of the paper.
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