Kev Txhim Kho Nyob Hauv Kev Siv Chiral 1,4-Diazepanes Cov Qauv Txheej Txheem Los Ntawm Enzymatic Intramolecular Asymmetric Reductive Amination

Insomnia yog ib qho kev pw tsaug zog uas muaj qhov tshwm sim hauv cov tib neeg. Suvorexan yog hom tshiab ntawm hypnotics. Nws yog thawj orexin receptor antagonist tau pom zoo los ntawm Asmeskas FDA xyoo 2014 rau kev kho mob ntawm kev nyuaj poob tsaug zog lossis tswj kev pw tsaug zog. Txawm li cas los xij, nws tseem nyuaj rau ua kom tau txais txiaj ntsig chiral 1,4-Diazepanes ntiv nplhaib, uas yog pawg tseem ceeb ntawm Suvoressen.

Lub biocatalysis thiab ntsuab chemical engineering pab neeg coj los ntawm Zhu Dunming thiab Wu Qiaqing, cov kws tshawb nrhiav ntawm Tianjin lub koom haum ntawm Industrial Biotechnology, Suav Academy ntawm Kev Tshawb Fawb, ua raws li kev siv imine reductase rau catalyze qhov txo qis asymmetric ntawm α, β-unsaturated imines los ua ke cov tseem ceeb intermediates. ntawm morphinane (Adv Synth. Catal. 2019, 361, 556-561), imine reductase catalyzed intramolecular asymmetric reductive amination los tsim chiral 1,4-Diazepanes sib txuas.

Txoj kev tshawb no pom tias ob lub enzymes nthuav tawm kev ua tiav stereoselectivity los ntawm kev tshuaj ntsuam lub tsev qiv ntawv imine reductase, thiab cov enantiomeric dhau ntawm (R) - lossis (S)-kev tsim cov khoom lag luam muaj ob qho tib si ntau dua 99%. Lub (R) -saib ua kom haum imine reductase uas ua rau Suvorexan intermediate tau hloov kho kom tau txais kev hloov pauv nrog 61-lub sijhawm ntxiv ntawm catalytic efficiency, thiab ob lub stereoselective complementary enzymes tau siv los coj los sib txawv ntawm cov qauv sib txawv ntawm Chiral 1,4-Diazepanes tebchaw muab cov qauv txheej txheem tshiab rau kev tsim cov tshuaj tshiab. Txoj kev tshawb no tau qhia txog cov ntsiab lus tseem ceeb rau kev txhim kho catalytic kev ua si ntawm mutant enzymes los ntawm kev ua kom tuab txoj kev suav thiab kev suav kev suav hais txog lub zog, thiab nthuav lub tswv yim ntawm kev hloov kho enzyme.

Cov kev tshawb fawb ua haujlwm tau txhawb nqa los ntawm cov kev tshawb fawb tseem ceeb hauv teb chaws thiab cov phiaj xwm kev txhim kho, cov dej num ntsig txog ntawm Suav Academy ntawm Kev Tshawb Fawb, thiab Tianjin Kev Tshawb Fawb Txog Kev Tshawb Fawb thiab Txuj Ci Tshuab. Cov kev tshawb fawb cuam tshuam tau nyuam qhuav tau luam tawm ntawm ACS Catalysis. Tus kws tshaj lij tus tub ntxhais kawm Xu Zefei thiab tus kws tshawb fawb nrog Yao Peiyuan los ntawm Tianjin lub koom haum thev naus laus zis yog tus sib koom ua ke thawj zaug ntawm daim ntawv.

Ntawv txuas ：https://pubs.acs.org/doi/10.1021/acscatal.0c02400