33149-64-3

Upstream product

• 33091-16-6 (+)-phthalic acid mono-(4-nitro-benzhydryl ester) 
• 33091-15-5 4-nitrophenyl(phenyl)methanol 
• 1144-74-7 4-nitrobenzophenone 
• 1078-58-6 diphenylzinc 
• 555-16-8 4-nitrobenzaldehdye 
• 98-80-6 phenylboronic acid 
• 16635-23-7 phenyltriisopropoxytitanium(IV) 
• 611-94-9 4-Methoxybenzophenone 
• 591-51-5 phenyllithium 

Downstream Products

• 73773-07-6 (S)-4-bromophenyl(phenyl)methanol 
• 101402-04-4 (S)-4-chlorobenzhydrol 
• 101402-03-3 (S)-(-)-p-acetamidobenzhydryl acetate 
• 7322-88-5 (S)-acetylmandelic acid 
• 101402-02-2 (S)-(4-aminophenyl)(phenyl)methanol 

Relevant academic research and scientific papers

Highly enantioselective asymmetric reactions involving zinc ions promoted by chiral aziridine alcohols

Enantiomerically pure, chiral secondary and tertiary aziridine alcohols (including the aziridine analogue of ProPhenol—AziPhenol) have proven to be highly effective catalysts for enantioselective asymmetric reactions in the presence of zinc ions, including arylation of aromatic aldehydes, epoxidation of chalcone and addition of diethylzinc to aldehydes, leading to the desired chiral products in high chemical yields (up to 90%) and with ee's up to 90%. A higher catalytic activity of Prophenol-type bis(aziridine alcohol) in the aforementioned asymmetric transformations has been demonstrated.

Palladium(ii) complexes with planar chiral ferrocenyl phosphane-(benz) imidazol-2-ylidene ligands

We describe here the first examples of planar chiral ferrocenyl phosphane-benzimidazol-2-ylidene ligands and their coordination chemistry with palladium(ii). All ligand precursors, namely enantiopure ferrocenyl phosphane-(benz)imidazolium salts, and all e

Candida zeylanoides as whole-cell biocatalyst to perform asymmetric bioreduction of benzophenone derivatives

Candida zeylanoides P1 was investigated as whole cell biocatalyst for the bioreduction of biaryl prochiral ketones into chiral carbinols, which can be used as pharmaceutical intermediate. Bioreduction of different biaryl ketones was carried out to their corresponding chiral biaryl carbinols such as (S)-(4-chlorophenyl) (phenyl) methanol (2a), which can be used in the synthesis of L-cloperastine drug, with antitussive, antiepidemic activity and bronchial musculature relaxant characteristics, in gram scale, enantiopure form (>99%) and excellent yields. The selectivity of C. zeylanoides P1 in enantioselective reduction of biaryl ketones was not affected by the steric and electronic effects of substrates. The current method demonstrates an encouraging green chemistry approach for the production of biaryl secondary chiral alcohols of pharmaceutical importance in mild, inexpensive and environmentally friendly process. The present study has many benefits since this yeast biocatalyst were successfully applied bioreduction of structurally bulky prochiral substrates, which cannot be reducted by chemical catalysis.

Molecular switch manipulating Prelog priority of an alcohol dehydrogenase toward bulky-bulky ketones

Structure-guided rational design revealed the molecular switch manipulating the Prelog and anti-Prelog priorities of an NADPH-dependent alcohol dehydrogenase toward prochiral ketones with bulky and similar substituents. Synergistic effects of unconserved residues at 214 and 237 in small and large substrate binding pockets were proven to be vital in governing the stereoselectivity. The ee values of E214Y/S237A and E214C/S237 G toward (4-chlorophenyl)-(pyridin-2-yl)-methanone were 99.3% (R) and 78.8% (S) respectively. Substrate specificity analysis revealed that similar patterns were also found with (4’-chlorophenyl)-phenylmethanone, (4’-bromophenyl)-phenylmethanone and (4’-nitrophenyl)-phenylmethanone. This study provides valuable evidence for understanding the molecular mechanism on enantioselective recognition of prochiral ketones by alcohol dehydrogenase.

Substituent Position-Controlled Stereoselectivity in Enzymatic Reduction of Diaryl- and Aryl(heteroaryl)methanones

We report here the discovery of a novel ketoreductase (KRED), named KmCR2, with a broad substrate spectrum on bioreduction of sterically bulky diaryl- and aryl(heteroaryl)methanones. The position of the substituent on aromatic rings (meta versus para or ortho) was revealed to control the stereospecificity of KmCR2. The stereoselective preparation of both enantiomers of diaryl- or aryl(heteroaryl)methanols using strategically engineered substrates with a traceless directing group (bromo group) showcased the potential application of this substrate-controlled bioreduction reaction. The combined use of substrate engineering and protein engineering, was demonstrated to be a useful strategy in efficiently improving stereoselectivity or switching stereopreference of enzymatic processes. (Figure presented.).

Synthesis and electrochemical characterization of iminophosphine-based ruthenium(II) complexes and application in asymmetric transfer hydrogenation reaction as catalysts

A range of Ru(II) complexes have been prepared with chiral iminophosphine ligands ([(2-PPh2)C6H4CH=NCH(CH3)C6H5(4-R)]; R = –H, p-CH3, p-NO2) and characterized by 1H, 13C, 31P{1H} NMR and FTIR spectroscopy. The electrochemical properties of the [Ru(PN)2Cl2] complexes were investigated in ACN/TBAP solution with cyclic voltammetry and square wave voltammetry techniques. The use of chiral [Ru(PN)2Cl2] complexes as catalysts for the asymmetric transfer hydrogenation of aromatic and aliphatic ketones was studied in 2-propanol in an attempt to demonstrate the effect of substituents, which attached to the phenyl ring bonded to the nitrogen donor, on the catalytic activity and enantioselectivity. It was seen that the electronic effects of these substituents did not contribute to the catalytic efficiency of the ruthenium(II) catalysts.

Conformational Dynamics-Guided Loop Engineering of an Alcohol Dehydrogenase: Capture, Turnover and Enantioselective Transformation of Difficult-to-Reduce Ketones

Directed evolution of enzymes for the asymmetric reduction of prochiral ketones to produce enantio-pure secondary alcohols is particularly attractive in organic synthesis. Loops located at the active pocket of enzymes often participate in conformational changes required to fine-tune residues for substrate binding and catalysis. It is therefore of great interest to control the substrate specificity and stereochemistry of enzymatic reactions by manipulating the conformational dynamics. Herein, a secondary alcohol dehydrogenase was chosen to enantioselectively catalyze the transformation of difficult-to-reduce bulky ketones, which are not accepted by the wildtype enzyme. Guided by previous work and particularly by structural analysis and molecular dynamics (MD) simulations, two key residues alanine 85 (A85) and isoleucine 86 (I86) situated at the binding pocket were thought to increase the fluctuation of a loop region, thereby yielding a larger volume of the binding pocket to accommodate bulky substrates. Subsequently, site-directed saturation mutagenesis was performed at the two sites. The best mutant, where residue alanine 85 was mutated to glycine and isoleucine 86 to leucine (A85G/I86L), can efficiently reduce bulky ketones to the corresponding pharmaceutically interesting alcohols with high enantioselectivities (～99% ee). Taken together, this study demonstrates that introducing appropriate mutations at key residues can induce a higher flexibility of the active site loop, resulting in the improvement of substrate specificity and enantioselectivity. (Figure presented.).

Hydroclassified Combinatorial Saturation Mutagenesis: Reshaping Substrate Binding Pockets of KpADH for Enantioselective Reduction of Bulky-Bulky Ketones

A hydroclassified combinatorial saturation mutagenesis (HCSM) strategy was proposed for reshaping the substrate binding pocket by dividing 20 amino acids into four groups based on their hydrophobicity and size. These smart HCSM libraries could significantly reduce screening effort especially for the simultaneous mutagenesis of three or more residues and lacking high throughput screening methods. Employing HCSM strategy, the stereoselectivity of KpADH, an alcohol dehydrogenase from Kluyveromyces polysporus, was efficiently improved to 99.4% ee. (4-Chlorophenyl)(pyridin-2-yl)methanone (CPMK), generally regarded as a "hard-to-reduce" ketone, was used as a model substrate, and its corresponding chiral alcohol products could be utilized as antihistamine precursors. The best variant 50C10 displayed higher binding affinity and catalytic efficiency toward CPMK with KM/kcat of 59.3 s-1·mM-1, 3.51-fold that of KpADH. Based on MD simulations, increased difference between two binding pockets, enhanced hydrophobicity, and π-π and halogen-alkyl interactions were proposed to favor the enantioselective recognition and substrate binding in 50C10. Substrate spectrum analysis revealed that 50C10 exhibited improved enantioselectivity toward diaryl ketones especially with halo- or other electron-withdrawing groups. As much as 500 mM CPMK could be asymmetrically reduced into chiral diaryl alcohols with ee of 99.4% and a space-time yield of 194 g·L-1·d-1 without addition of external NADP+. This study provides an effective mutagenesis strategy for the protein engineering of substrate specificity and enantioselectivity.

Asymmetric Transfer Hydrogenation of (Hetero)arylketones with Tethered Rh(III)-N-(p-Tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine Complexes: Scope and Limitations

A series of new tethered Rh(III)/Cp? complexes containing the N-(p-tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine ligand have been prepared, characterized, and evaluated in the asymmetric transfer hydrogenation (ATH) of a wide range of (hetero)aryl ketones. The reaction was performed under mild conditions with the formic acid/triethylamine (5:2) system as the hydrogen source and provided enantiomerically enriched alcohols with good yields and high to excellent enantioselectivities. Although the nature of the substituents on the phenyl tethering ring did not alter the stereochemical outcome of the reaction, complexes bearing electron-donating groups exhibited a higher catalytic activity than those having electron-withdrawing groups. A scale-up of the ATH of 4-chromanone to the gram scale quantitatively delivered the reduced product with excellent enantioselectivity, demonstrating the potential usefulness of these new complexes.

Efficient Access to Chiral Benzhydrols via Asymmetric Transfer Hydrogenation of Unsymmetrical Benzophenones with Bifunctional Oxo-Tethered Ruthenium Catalysts

A concise asymmetric transfer hydrogenation of diaryl ketones, promoted by bifunctional Ru complexes with an etherial linkage between 1,2-diphenylethylenediamine (DPEN) and η6-arene ligands, was successfully developed. Because of the effective discrimination of substituents at the ortho position on the aryl group, unsymmetrical benzophenones were smoothly reduced in a 5:2 mixture of formic acid and triethylamine with an unprecedented level of excellent enantioselectivity. For the non-ortho-substituted benzophenones, the oxo-tethered catalyst electronically discerned biased substrates, resulting in attractive performance yielding chiral diarylmethanols with >99% ee.