6290-03-5Relevant articles and documents
Introduction of Hindered Electrophiles via C-H Functionalization in a Palladium-Catalyzed Multicomponent Domino Reaction
Qureshi, Zafar,Schlundt, Waldemar,Lautens, Mark
, p. 2446 - 2456 (2015)
A general method for the incorporation of secondary alkyl iodides in a palladium-catalyzed multicomponent domino reaction is reported. With the relatively inexpensive Pd(OAc)2 as the catalyst and norbornene as a mediator, a variety of 1,2,3-trisubstituted aromatic compounds were synthesized. The reaction was shown to be scalable, producing excellent isolated yields on up to 5 mmol scale. Chiral alkyl iodides were also incorporated without any loss of stereochemical information. The developed method offers an expedient and mild C-H functionalization strategy for the synthesis of sterically congested aromatic compounds in a one-pot process.
Chiral tetradentate ligand, chiral ruthenium complex and method for preparing (R)-(-)-1, 3-butanediol
-
Paragraph 0088-0089, (2021/03/24)
The invention discloses a chiral tetradentate ligand, a chiral ruthenium complex and a method for preparing (R)-(-)-1, 3-butanediol. The structural formula of the ligand is preferred, and R1 and R2 are H, Br, tert-butyl, phenyl, 3, 5-trifluoromethyl phenyl which are independent of each other. The method overcomes the defects of high cost, large catalyst dosage, difficulty in product separation andthe like in the existing technology for preparing (R)-(-)-1, 3-butanediol, and can perform asymmetric hydrogenation on carbonyl of the substrate methyl acetoacetate and reduce the ester group to obtain (R)-(-)-1, 3-butanediol by using a low-cost and small-dosage catalyst. The reaction operation process is simple, the catalyst is simple to prepare, and the yield and ee value of the target productare 98% or above. Meanwhile, the catalyst can be used for five times, so that the cost is greatly reduced, and the potential of industrial application is achieved.
Rational engineering of 2-deoxyribose-5-phosphate aldolases for the biosynthesis of (R)-1,3-butanediol
Kim, Taeho,Stogios, Peter J.,Khusnutdinova, Anna N.,Nemr, Kayla,Skarina, Tatiana,Flick, Robert,Joo, Jeong Chan,Mahadevan, Radhakrishnan,Savchenko, Alexei,Yakunin, Alexander F.
, p. 597 - 609 (2020/01/21)
Carbon– carbon bond formation is one of the most important reactions in biocatalysis and organic chemistry. In nature, aldolases catalyze the reversible stereoselective aldol addition between two carbonyl compounds, making them attractive catalysts for the synthesis of various chemicals. In this work, we identified several 2-deoxyribose-5-phosphate aldolases (DERAs) having acetaldehyde condensation activity, which can be used for the biosynthesis of (R)-1,3-butanediol (1,3BDO) in combination with aldo-keto reductases (AKRs). Enzymatic screening of 20 purified DERAs revealed the presence of significant acetaldehyde condensation activity in 12 of the enzymes, with the highest activities in BH1352 from Bacillus halodurans, TM1559 from Thermotoga maritima, and DeoC from Escherichia coli. The crystal structures of BH1352 and TM1559 at 1.40 –2.50 ? resolution are the first full-length DERA structures revealing the presence of the C-terminal Tyr (Tyr224 in BH1352). The results from structure-based site-directed mutagenesis of BH1352 indicated a key role for the catalytic Lys155 and other active-site residues in the 2-deoxyribose-5-phosphate cleavage and acetaldehyde condensation reactions. These experiments also revealed a 2.5-fold increase in acetaldehyde transformation to 1,3BDO (in combination with AKR) in the BH1352 F160Y and F160Y/M173I variants. The replacement of the WT BH1352 by the F160Y or F160Y/M173I variants in E. coli cells expressing the DERA + AKR pathway increased the production of 1,3BDO from glucose five and six times, respectively. Thus, our work provides detailed insights into the molecular mechanisms of substrate selectivity and activity of DERAs and identifies two DERA variants with enhanced activity for in vitro and in vivo 1,3BDO biosynthesis.
