16369-14-5Relevant articles and documents
Data mining of amine dehydrogenases for the synthesis of enantiopure amino alcohols
Guo, Jinggong,Li, Jun-Kuan,Ma, Jun-An,Miao, Yuchen,Qu, Ge,Sun, Zhoutong,Wang, Hongyue
, p. 5945 - 5952 (2020/10/08)
Chiral amino alcohols are essential building blocks for the pharmaceutical industry, and are widely present in natural and synthetic bioactive compounds. Amine dehydrogenases (AmDHs) can asymmetrically reduce prochiral ketones with low-cost ammonia to chiral amines and water as by-products, using NAD(P)H as a cofactor under mild conditions, but hydroxy ketones with formation of chiral hydroxy amines have rarely been investigated. In this study, six new bacterial AmDHs derived from amino acid dehydrogenases (AADHs) were identified by data mining, and five out of the six enzymes were able to efficiently reduce 1-hydroxybutan-2-one (1a) to (S)-2-aminobutan-1-ol ((S)-2a) with 19-99% conversions and 99% ee. The five AmDHs were purified and biochemically characterized for reductive amination activity towards substrate 1a with the optimal pH at 8.5 or 9.0 and the optimal temperature at 45 °C, 50 °C or 55 °C, and provided reductive amination of a broad range of prochiral α-hydroxy ketones, and even of a model β-hydroxy ketone leading to β-hydroxy amine with 99% ee. Our study expands the toolbox of AmDHs in the synthesis of chiral amino alcohols.
Palladium-N-heterocyclic carbene (NHC)-catalyzed asymmetric synthesis of indolines through regiodivergent C(sp3)-H activation: Scope and DFT study
Katayev, Dmitry,Larionov, Evgeny,Nakanishi, Masafumi,Besnard, Cline,Kündig, E. Peter
supporting information, p. 15021 - 15030 (2015/02/19)
Two bulky, chiral, monodentate N-heterocyclic carbene ligands were applied to palladium-catalyzed asymmetric C-H arylation to incorporate C(sp3)-H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans-2,3- substituted indolines. Although this CAr-Calkyl coupling requires high temperatures (140-160°C), chiral induction is high. This regiodivergent reaction, when carried out with enantiopure starting materials, can lead to single structurally different enantiopure products, depending on the catalyst chirality. The C-H activation at a tertiary center was realized only in the case of a cyclopropyl group. No C-H activation takes place alpha to a tertiary center. A detailed DFT study is included and analyses of methyl versus methylene versus methine C-H activation is used to rationalize experimentally observed regio- and enantioselectivities.
Diastereoselective synthesis of enantiopure homopropargylic n-tert-butylsulfinylamines
Cyklinsky, Mathieu,Botuha, Candice,Chemla, Fabrice,Ferreira, Franck,Pérez-Luna, Alejandro
experimental part, p. 2681 - 2684 (2011/12/04)
The diastereoselective synthesis of enantiopure homopropargylic amines by propargylation of various N-tert-butylsulfinylimines (tBS-imines) with 1-trimethylsilyl allenylzinc bromide is presented. Georg Thieme Verlag Stuttgart · New York.
