Chiral synthesis via organoboranes. 34. Selective reductions. 47. Asymmetric reduction of hindered .alpha.,.beta.-acetylenic ketones with B-chlorodiisopinocampheylborane to propargylic alcohols of very high enantiomeric excess. Improved workup procedure for the isolation of product alcohols

1992 ◽  
Vol 57 (8) ◽  
pp. 2379-2386 ◽  
Author(s):  
P. Veeraraghavan Ramachandran ◽  
Aleksandar V. Teodorovic ◽  
Milind V. Rangaishenvi ◽  
Herbert C. Brown
Keyword(s):  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
Chiral Synthesis ◽  
Propargylic Alcohols ◽  
Alpha Beta ◽  
Very High

scholarly journals Chemoenzymatic Synthesis of Synthes as Precursors for Enantiopure Clenbuterol and Other β2 Agonists

Catalysts ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 516
Author(s):  
Fredrik Blindheim ◽  
Mari Hansen ◽  
Sigvart Evjen ◽  
Wei Zhu ◽  
Elisabeth Jacobsen
Keyword(s):  
Protein Synthesis ◽  
Nicotinamide Adenine Dinucleotide ◽  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
The Body ◽  
Chemoenzymatic Synthesis ◽  
The World ◽  
Β2 Agonist ◽  
Β2 Agonists

Clenbuterol is a β2-agonist used in the veterinary treatment of asthma in several countries. The drug is listed on the World Antidoping Agency’s prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, pure enantiomers need to be separately studied. (R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor in dimethyl sulfoxide (DMSO). (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers.

scholarly journals Efficient Biocatalytic Preparation of Optically Pure (R)-1-[4-(Trifluoromethyl)phenyl]ethanol by Recombinant Whole-Cell-Mediated Reduction

Catalysts ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 391 ◽  
Author(s):  
Ying Chen ◽  
Nana Xia ◽  
Yuewang Liu ◽  
Pu Wang
Keyword(s):  
Organic Solvent ◽  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
Aqueous System ◽  
Cell Membrane Permeability ◽  
Buffer Solution ◽  
Preparative Scale ◽  
Buffer Medium ◽  
Polar Organic Solvent ◽  
Optically Pure

(R)-1-[4-(Trifluoromethyl)phenyl]ethanol is an important pharmaceutical intermediate of a chemokine CCR5 antagonist. In the present study, a bioprocess for the asymmetric reduction of 4-(trifluoromethyl)acetophenone to (R)-1-[4-(trifluoromethyl)phenyl]ethanol was developed by recombinant Escherichia coli cells with excellent enantioselectivity. In order to overcome the conversion limitation performed in the conventional buffer medium resulting from poor solubility of non-natural substrate, we subsequently established a polar organic solvent-aqueous medium to improve the efficacy. Isopropanol was selected as the most suitable cosolvent candidate, based on the investigation on a substrate solubility test and cell membrane permeability assay in different organic solvent-buffer media. Under the optimum conditions, the preparative-scale asymmetric reduction generated a 99.1% yield with >99.9% product enantiomeric excess (ee) in a 15% (v/v) isopropanol proportion, at 100 mM of 4-(trifluoromethyl)acetophenone within 3 h. Compared to bioconversion in the buffer medium, the developed isopropanol-aqueous system enhanced the substrate concentration by 2-fold with a remarkably improved yield (from 62.5% to 99.1%), and shortened the reaction time by 21 h. Our study gave the first example for a highly enantioselective production of (R)-1-[4-(trifluoromethyl)phenyl]ethanol by a biological method, and the bioreduction of 4-(trifluoromethyl)acetophenone in a polar organic solvent-aqueous system was more efficient than that in the buffer solution only. This process is also scalable and has potential in application.

A Novel Asymmetric reduction of Nitroolefin 2-Nitro-1-Phenyl-1-Propene by Using BINAP-Ruthenium(II) Complexes

2003 ◽  
Vol 2003 (3) ◽  
pp. 128-129 ◽  
Author(s):  
Yanjun Li ◽  
Taeko Izumi
Keyword(s):  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
Optically Active

The ruthenium BINAP complex, [Ru(OAc)2{(S)-BINAP}], can catalyse the hydrogenation of 2-nitro-1-phenyl-1-propene (1) to give optically active 2-nitro-1-phenylpropane (2) in moderate enantiomeric excess.

Efficient general asymmetric syntheses of 3-substituted 1(3H)-isobenzofuranones in very high enantiomeric excess

1996 ◽  
Vol 37 (13) ◽  
pp. 2205-2208 ◽  
Author(s):  
P.Veeraraghavan Ramachandran ◽  
Guang-Ming Chen ◽  
Herbert C. Brown
Keyword(s):  
Enantiomeric Excess ◽  
Asymmetric Syntheses ◽  
Substituted 1 ◽  
Very High

scholarly journals Identification, Cloning, and Characterization of a Novel Ketoreductase from the Cyanobacterium Synechococcus sp. Strain PCC 7942

2008 ◽  
Vol 74 (21) ◽  
pp. 6697-6702 ◽  
Author(s):  
Kathrin H�lsch ◽  
Jan Havel ◽  
Martin Haslbeck ◽  
Dirk Weuster-Botz
Keyword(s):  
Specific Activity ◽  
Acyl Carrier Protein ◽  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
High Specific Activity ◽  
Lactobacillus Brevis ◽  
Ph Optimum ◽  
Synechococcus Sp ◽  
Prochiral Ketones ◽  
Pcc 7942

ABSTRACT A new ketoreductase useful for asymmetric synthesis of chiral alcohols was identified in the cyanobacterium Synechococcus sp. strain PCC 7942. Mass spectrometry of trypsin-digested peptides identified the protein as 3-ketoacyl-[acyl-carrier-protein] reductase (KR) (EC 1.1.1.100). The gene, referred to as fabG, was cloned, functionally expressed in Escherichia coli, and subsequently purified to homogeneity. The enzyme displayed a temperature optimum at 44�C and a broad pH optimum between pH 7 and pH 9. The NADPH-dependent KR was able to asymmetrically reduce a variety of prochiral ketones with good to excellent enantioselectivities (>99.8%). The KR showed particular high specific activity for asymmetric reduction of ethyl 4-chloroacetoacetate (38.29 � 2.15 U mg−1) and 2′,3′,4′,5′,6′-pentafluoroacetophenone (8.57 � 0.49 U mg−1) to the corresponding (S)-alcohols. In comparison with an established industrial enzyme like the alcohol dehydrogenase from Lactobacillus brevis, the KR showed seven-times-higher activity toward 2′,3′,4′,5′,6′-pentafluoroacetophenone, with a remarkably higher enantiomeric excess (>99.8% [S] versus 43.3% [S]).

scholarly journals Chemo-Enzymatic Synthesis of Synthons as Precursors for Enantiopure Clenbuterol and other β2- Agonists

2018 ◽  
Author(s):  
Fredrik Heen Blindheim ◽  
Mari Bergan Hansen ◽  
Sigvart Evjen ◽  
Wei Zhu ◽  
Elisabeth Egholm Jacobsen
Keyword(s):  
Protein Synthesis ◽  
Enzymatic Synthesis ◽  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
The Body ◽  
Industrial Scale ◽  
The World ◽  
World Anti Doping Agency ◽  
Beta 2

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β2-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Sign in / Sign up

Export Citation Format

Share Document