- Exploration of the biocatalytic potential of a halohydrin dehalogenase using chromogenic substrates
-
Halohydrin dehalogenases are bacterial enzymes that catalyse the reversible formation of epoxides from vicinal halohydrins. A spectrophotometric assay for halohydrin dehalogenases based on the absorption difference between the halohydrin para-nitro-2-bromo-1-phenylethanol and the epoxide para-nitrostyrene oxide was developed. The enantioselectivity of ring-closure reactions catalysed by three different halohydrin dehalogenases could be estimated from the shape of progress curves. Evaluation of ring-opening reactions catalysed by halohydrin dehalogenase from Agrobacterium radiobacter AD1 established that, in addition to Cl- and Br-, nucleophiles such as N3-, CN- and NO2- are also accepted for the ring opening of para-nitrostyrene oxide. The ring-opening reactions with these nucleophiles resulted in highly enantioselective kinetic resolutions, which expands the scope of synthetically valuable conversions catalysed by a halohydrin dehalogenase.
- Lutje Spelberg, Jeffrey H.,Tang, Lixia,Van Gelder, Marc,Kellogg, Richard M.,Janssen, Dick B.
-
-
Read Online
- Highly enantioselective and regioselective biocatalytic azidolysis of aromatic epoxides
-
(equation presented) The halohydrin dehalogenase from Agrobacterium radiobacter AD1 catalyzed the highly enantioselective and β-regioselective azidolysis of (substituted) styrene oxides. By means of kinetic resolutions the remaining epoxide and the formed azido alcohol could be obtained in very high ee. In a large scale conversion, the decrease in yield and selectivity due to the uncatalyzed chemical side reaction could be overcome by slow addition of azide.
- Spelberg, Jeffrey H. Lutje,Van Vlieg, Johan E. T. Hylckama,Tang, Lixia,Janssen, Dick B.,Kellogg, Richard M.
-
-
Read Online
- Synthesis of β-adrenergic blockers (R)-(-)-nifenalol and (S)-(+)-sotalol via a highly efficient resolution of a bromohydrin precursor
-
(R)- and (S)-2-bromo-1-(4-nitrophenyl)ethanol are precursors of important β-adrenergic receptor blocking drugs (R)-nifenalol and (S)-sotalol, respectively. Both were obtained in enantiomeric pure forms via a single highly efficient enzymatic transesterification reaction of (±)-2-bromo-1-(4- nitrophenyl)ethanol using immobilized lipase PS-C-II (E >1000; concn 200 g/L), while PS lipase completely failed to react. On the other hand, the hydrolytic method also produced enantiorich precursors though relatively less efficient (PS-C-II, E = 5.1). Out of all the approaches employed the transesterification method proved to be the most efficient.
- Kapoor, Munish,Anand, Naveen,Ahmad, Khursheed,Koul, Surrinder,Chimni, Swapandeep S.,Taneja, Subhash C.,Qazi, Ghulam N.
-
-
Read Online
- Microbiological bio-reduction of prochiral carbonyl compounds by antimycotic agent Boni Protect
-
The selective properties of the fungus Aureobasidium pullulans, in the antifungal agent Boni Protect, were investigated in the fermentative bioreduction of selected carbonyl compounds. Catalyzed by oxidoreductases contained in the microorganism Aureobasidium pullulans highly enantioselective biotransformation of prochiral ketones provides the secondary alcohols when the reaction is done in the presence of specific additives. Aureobasidium pullulans has also proved to be an effective bioreagent in the reduction of α- and β-keto esters. Optically pure hydroxy esters were obtained under fermentation conditions without the use of additives.
- Ko?odziejska, Renata,Studzińska, Renata,Kwit, Marcin,Jelecki, Maciej,Tafelska-Kaczmarek, Agnieszka
-
-
- Integration of multiple active sites on large-pore mesoporous silica for enantioselective tandem reactions
-
Facile construction of a multifunctional heterogeneous catalyst through the assembly of Au/carbene and chiral ruthenium/diamine dual complexes in large-pore mesoporous silica was developed. This enables an efficient one-pot hydration-asymmetric transfer hydrogenation enantioselective tandem reaction of haloalkynes, affording chiral halohydrins with up to 99% enantioselectivity. Combined multifunctionalities, such as substrate-promoted silanol-functionality, BF4? anion-bonding gold/carbene and covalent-bonding chiral ruthenium/diamine active centers, contributed cooperatively to the catalytic performance.
- Xia, Xuelin,Meng, Jingjing,Wu, Hanxin,Cheng, Tanyu,Liu, Guohua
-
supporting information
p. 1638 - 1641
(2017/02/10)
-
- One-Pot cascade hydration-asymmetric transfer hydrogenation as a practical strategy to construct chiral β-adrenergic receptor blockers
-
The facile construction of biologically active β-adrenergic receptor agonists/blockers and analogues is a great fundamental and practical challenge in medical chemistry. Herein, we report a hydration-asymmetric transfer hydrogenation cascade to realize the one-pot enantioselective transformation of aromatic haloalkynes into chiral aromatic halohydrins, which can be converted readily into chiral β-adrenergicreceptor blockers. Such a one-pot cascade process involves the Au-catalyzed hydration of aryl-substituted haloalkynes to aryl-substituted α-halomethyl ketones and the Ru-catalyzed asymmetric transfer hydrogenation of aryl-substituted α-halomethyl ketones to aryl-substituted 2-haloethanols. The significant benefits of this procedure are that it provides chiral aromatic halohydrins in high yields, with excellent enantioselectivities, and a wide variety of functional groups are tolerated under mild conditions. The study described herein offers a useful approach to construct chiral β-adrenergic blockers, which is an attractive practical organic transformation that is performed in a one-pot manner.
- Ye, Qunqun,Cheng, Tanyu,Zhao, Yuxi,Zhao, Junwei,Jin, Ronghua,Liu, Guohua
-
p. 1801 - 1805
(2015/06/23)
-
- Surfactant-accelerated asymmetric transfer hydrogenation with recyclable water-soluble catalyst in aqueous media
-
Water-soluble ligands (R,R)-2 were successfully prepared, in which the bis-meta-sulphonated ligand was definitely detected as the major product. The corresponding transition-metal complexes containing the ligands displayed excellent catalytic performance in asymmetric transfer hydrogenation (ATH) of aromatic ketones. Especially, the aromatic ketones with a bromine group in the α position could be smoothly reduced to the expected alcohol, keeping the bromine group intact with excellent enantioselectivities (up to 96% ee). The catalyst could be reused at least 21 times without erosion of the enantioselectivity in high conversion. Moreover, it was found that cationic surfactant and proper pH values were necessary for the maintenance of high reactivity.
- Li, Jiahong,Li, Xuefeng,Ma, Yaping,Wu, Jiashou,Wang, Fei,Xiang, Jing,Zhu, Jin,Wang, Qiwei,Deng, Jingen
-
p. 1825 - 1834
(2013/03/14)
-
- A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane
-
A novel C3-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivities (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation and re-used for four cycles without losing the selectivity. Copyright
- Wu, Xiang-Fei,Min, Chang,Nyamzundui, Enkhtsetseg,Zhou, Hai-Bing,Dong, Chune
-
experimental part
p. 1640 - 1643
(2011/12/22)
-
- Asymmetric synthesis of β-adrenergic blockers through multistep one-pot transformations involving in situ chiral organocatalyst formation
-
Two birds one stone: A new atom-economical one-pot approach to enantioselective chiral drug synthesis, involving in situ multistep organocatalyst formation and the application of the reaction for multistep sequential synthesis of β-adrenergic blockers is disclosed (see scheme).
- Wei, Shengwei,Messerer, Regina,Tsogoeva, Svetlana B.
-
supporting information; scheme or table
p. 14380 - 14384
(2012/02/01)
-
- Chemo- And stereodivergent preparation of terminal epoxides and bromohydrins through One-Pot biocatalysed reactions: Access to enantiopure Five- and Six-Membered N-Heterocycles
-
Different enantiopure terminal epoxides or bromohydrins have chemoselectively been synthesised in one-pot starting from the corresponding a-bromo ketones through alcohol dehydrogenase (ADH)-catalysed processes adding an organic cosolvent and tuning appropriately the medium pH and the temperature. Thus, at neutral pH enantiopure bromohydrins were obtained while using basic conditions (pH 9.5-10) epoxides were isolated as the main product. Furthermore, by simple selection of the biocatalyst, chemo- and stereodivergent transformations were achieved to obtain, e.g., enantiopure prolinol or piperidin-3-ol.
- Bisogno, Fabricio R.,Cuetos, Anibal,Orden, Alejandro A.,Kurina-Sanz, Marcela,Lavandera, Ivan,Gotor, Vicente
-
supporting information; experimental part
p. 1657 - 1661
(2010/09/18)
-
- (5S)-1-Aza-2-imino-3-oxa-4,4-diphenylbicyclo(3.3.0)octane: a novel chiral catalytic source containing the N-(C{double bond, long}NH)-O moiety for the borane-mediated asymmetric reduction of prochiral ketones
-
(5S)-1-Aza-2-imino-3-oxa-4,4-diphenylbicyclo(3.3.0)octane, a novel chiral catalytic source containing the N-(C{double bond, long}NH)-O moiety, has been synthesized and successfully utilized, for the first time, as a chiral catalytic source in the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene, to provide the corresponding secondary alcohols with up to 93% enantiomeric excess.
- Basavaiah, Deevi,Venkateswara Rao, Kalapala,Sekhara Reddy, Bhavanam
-
p. 963 - 967
(2008/02/03)
-
- (5S)-1,3-Diaza-2-imino-3-phenylbicyclo[3.3.0]octane: first example of guanidine based in situ recyclable chiral catalytic source for borane-mediated asymmetric reduction of prochiral ketones
-
(5S)-1,3-Diaza-2-imino-3-phenylbicyclo[3.3.0]octane has been synthesized and successfully employed, for the first time, as a chiral catalytic source for the borane-mediated asymmetric reduction of prochiral α-halo ketones to provide the corresponding secondary alcohols in high enantiomeric purity. The potential of this guanidine as an in situ recyclable chiral catalytic source for the borane-mediated chiral reduction processes has also been demonstrated.
- Basavaiah, Deevi,Venkateswara Rao, Kalapala,Sekhara Reddy, Bhavanam
-
p. 1036 - 1040
(2007/10/03)
-
- (2S)-2-Anilinomethylpyrrolidine: an efficient in situ recyclable chiral catalytic source for the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene
-
(2S)-2-Anilinomethylpyrrolidine was successfully utilized as a chiral catalytic source in the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene to provide the corresponding secondary alcohols with enantiomeric excesses up to 91%. The potential of (2S)-2-anilinomethylpyrrolidine as an in situ recyclable chiral catalytic source in the borane-mediated chiral reduction processes has also been demonstrated.
- Basavaiah, Deevi,Rao, Kalapala Venkateswara,Reddy, Bhavanam Sekhara
-
p. 1041 - 1044
(2007/10/03)
-
- Asymmetric reduction of ketones by employing Rhodotorula sp. AS2.2241 and synthesis of the β-blocker (R)-nifenalol
-
A broad range of prochiral ketones were efficiently reduced to the corresponding optically active secondary alcohols using resting cells of Rhodotorula sp. AS2.2241. The microbial reduction system exhibited high activity and enantioselectivity in the reduction of various aromatic ketones and acetylpyridines (>97% ee), but moderate to high enantioselectivity in the reduction of α- and β-keto esters. (R)-Nifenalol, a β-adrenergic blocker, was also synthesized using 2-bromo-1(R)-(4-nitrophenyl)ethanol (97% ee) which was prepared through the asymmetric reduction of 2-bromo-1-(4-nitrophenyl)ethanone employing Rhodotorula sp. AS2.2241. The simple preparation and the high activity of the biocatalyst turned this system into a versatile tool for organic synthesis.
- Yang, Wei,Xu, Jian-He,Xie, Yan,Xu, Yi,Zhao, Gang,Lin, Guo-Qiang
-
p. 1769 - 1774
(2007/10/03)
-
- Asymmetric transfer hydrogenation of ketones catalyzed by hydrophobic metal-amido complexes in aqueous micelles and vesicles
-
Asymmetric transfer hydrogenation of ketones, especially α-bromomethyl aromatic ketones, catalyzed by unmodified, hydrophobic transition metal-amido complexes (TsDPEN-M), was performed successfully with significant enhancement of activity, chemoselectivity, and enantio-selectivity (up to 99% ee) in aqueous media containing micelles and vesicles. The hydrophobic catalyst, embedded in micelles constructed from the surfactant cetyltrimethylammonium bromide (CTAB), could be separated from the organic phase along with the products and was recycled for at least six times.
- Wang, Fei,Liu, Hui,Cun, Linfeng,Zhu, Jin,Deng, Jingen,Jiang, Yaozhong
-
p. 9424 - 9429
(2007/10/03)
-
- A new chiral catalytic source with an N-P=O structural framework containing a proximal hydroxyl group for the borane-mediated asymmetric reduction of prochiral ketones
-
(5S)-2-[(1R,2R,3S,5R)-2-Hydroxy-2,6,6-trimethylbicyclo[3.1.1] heptan-3-yloxy]-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo[3.3.0]octane has been successfully employed as a novel chiral catalytic source (4mol%) for borane-mediated asymmetric reduction of prochiral ketones thus providing the resulting secondary alcohols with up to 96% enantiomeric excess.
- Basavaiah, Deevi,Reddy, Gone Jayapal,Chandrashekar, Vanampally
-
-
- Toward effective chiral catalysts containing the N-P=O structural framework for the borane-mediated asymmetric reduction of prochiral ketones
-
Representative chiral catalysts containing the N-P=O structural framework having (5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo[3.3.0]octane moiety with amino groups of varying steric requirements on phosphorus, have been synthesized and their applications in the borane-mediated asymmetric reduction of prochiral ketones described.
- Basavaiah, Deevi,Reddy, Gone Jayapal,Rao, Kalapala Venkateswara
-
p. 1881 - 1888
(2007/10/03)
-
- (2S,5S)-1,3-Diaza-2-phospha-2-oxo-2-chloro-3-phenylbicyclo[3.3.0]octane: A novel chiral source for borane-mediated catalytic chiral reductions
-
(2S,5S)-1,3-Diaza-2-phospha-2-oxo-2-chloro-3-phenylbicyclo[3.3.0]octane has been successfully employed as a chiral catalytic source for the borane mediated asymmetric reductions of prochiral α-halo ketones to provide the desired (S)-secondary alcohols in 81-91% enantiomeric purities, thus for the first time demonstrating the potential of the N-P(=O)Cl structural framework to generate a recoverable, reusable and air stable catalyst for the asymmetric reduction processes.
- Basavaiah, Deevi,Jayapal Reddy, Gone,Chandrashekar, Vanampally
-
p. 1125 - 1128
(2007/10/03)
-
- cis-1-Amino-2-indanol in asymmetric synthesis. Part I. A practical catalyst system for the enantioselective borane reduction of aromatic ketones
-
A new class of oxazaborolidine catalysts has been prepared from optically pure cis-1-amino-2 indanols which are available in large quantities. The asymmetric borane reduction of aromatic ketones using these catalysts has been studied.
- Hong, Yaping,Gao, Yun,Nie, Xiaoyi,Zepp, Charles M.
-
p. 6631 - 6634
(2007/10/02)
-
