Unraveling the mechanism of enantio-controlling switches of an alcohol dehydrogenase toward sterically small ketone

Abstract

Efficient synthesis of chiral compounds under mild conditions is highly desirable in the chemical and pharmaceutical communities, but it often faces difficulties. Although various enzymes have been harnessed as biocatalysts...

Structure-guided semi-rational design of an imine reductase for enantio-complementary synthesis of pyrrolidinamine

“…26,28,29 Alternatively, rationally engineering an enzyme, which shows high catalytic efficiency for target substrates, to obtain enantio-preference enzymes is a highly efficient method. [34][35][36][37][38] Rational design usually focuses on a minority of potential amino acids, which can signicantly reduce the number of mutants to be investigated. 37,38 Although several advances focusing on tuning enzymatic catalytic efficiency have been reported, 26,28,29 rational design of IREDs for stereo-divergent reductive amination to synthesize both stereoisomers is relatively undeveloped.…”

“…34–38 Rational design usually focuses on a minority of potential amino acids, which can significantly reduce the number of mutants to be investigated. 37,38 Although several advances focusing on tuning enzymatic catalytic efficiency have been reported, 26,28,29 rational design of IREDs for stereo-divergent reductive amination to synthesize both stereoisomers is relatively undeveloped.…”

Atroposelective Synthesis of Aldehydes via Alcohol Dehydrogenase-Catalyzed Stereodivergent Desymmetrization

“…In summary, the recognition of proatropisomeric substrates and origin of atroposelectivity of ADHs are distinct from the center-chiral substrates where the dihedral angle for the hydride transfer to the carbonyl groups on the substrates is the major contributing factor to the configuration of the products. 59,60 ■ CONCLUSIONS In summary, we have developed the highly efficient asymmetric synthesis of axially chiral biaryls and diaryl ethers by ADH-catalyzed desymmetrization. Several ADHs were identified and characterized to catalyze the formation of a range of atropisomeric monoaldehydes in moderate to excellent ee and yields with both (R)-and (S)-configuration.…”

“…Therefore, with only the replacement of fluoro- to methoxy-substitution at the naphthyl rings of the substrates, the configuration of the products is reversed. In summary, the recognition of pro-atropisomeric substrates and origin of atroposelectivity of ADHs are distinct from the center-chiral substrates where the dihedral angle for the hydride transfer to the carbonyl groups on the substrates is the major contributing factor to the configuration of the products. , …”

“…In summary, the recognition of pro-atropisomeric substrates and origin of atroposelectivity of ADHs are distinct from the center-chiral substrates where the dihedral angle for the hydride transfer to the carbonyl groups on the substrates is the major contributing factor to the configuration of the products. 59 , 60 …”