- Catalytic Asymmetric Nitroaldol Reaction: An Efficient Synthesis of (S) Propranolol Using the Lanthanum Binaphthol Complex
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(S) Propranolol, a more potent optical isomer of the widely used β-blocker, was conveniently synthesized in a highly enantioselective manner by the lanthanum-(R)-(+)-binaphthol complex catalyzed asymmetric nitroaldol reaction.
- Sasai, Hiroaki,Itoh, Noriie,Suzuki, Takeyuki,Shibasaki, Masakatsu
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- Covalent Organic Frameworks with Chirality Enriched by Biomolecules for Efficient Chiral Separation
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The separation of racemic compounds is important in many fields, such as pharmacology and biology. Taking advantage of the intrinsically strong chiral environment and specific interactions featured by biomolecules, here we contribute a general strategy is developed to enrich chirality into covalent organic frameworks (COFs) by covalently immobilizing a series of biomolecules (amino acids, peptides, enzymes) into achiral COFs. Inheriting the strong chirality and specific interactions from the immobilized biomolecules, the afforded biomolecules?COFs serve as versatile and highly efficient chiral stationary phases towards various racemates in both normal and reverse phase of high-performance liquid chromatography (HPLC). The different interactions between enzyme secondary structure and racemates were revealed by surface-enhanced Raman scattering studies, accounting for the observed chiral separation capacity of enzymes?COFs.
- Zhang, Sainan,Zheng, Yunlong,An, Hongde,Aguila, Briana,Yang, Cheng-Xiong,Dong, Yueyue,Xie, Wei,Cheng, Peng,Zhang, Zhenjie,Chen, Yao,Ma, Shengqian
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supporting information
p. 16754 - 16759
(2018/11/27)
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- Ultrafast chiral separations for high throughput enantiopurity analysis
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Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.
- Barhate, Chandan L.,Joyce, Leo A.,Makarov, Alexey A.,Zawatzky, Kerstin,Bernardoni, Frank,Schafer, Wes A.,Armstrong, Daniel W.,Welch, Christopher J.,Regalado, Erik L.
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supporting information
p. 509 - 512
(2017/01/13)
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- Establishment and Evaluation of the Novel Tetramethylammonium-L-Hydroxyproline Chiral Ionic Liquid Synergistic System Based on Clindamycin Phosphate for Enantioseparation by Capillary Electrophoresis
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Much attention has been paid to chiral ionic liquids (ILs) in analytical chemistry, especially its application in capillary electrophoresis (CE) enantioseparation. However, the investigation of chiral ionic liquids synergistic systems based on antibiotic chiral selectors has been reported in only one article. In this work, a novel chiral ionic liquid, tetramethylammonium-L-hydroxyproline (TMA-L-Hyp), was applied for the first time in CE chiral separation to evaluate its potential synergistic effect with clindamycin phosphate (CP) as the chiral selector. As observed, significantly improved separation was obtained in this TMA-L-Hyp/CP synergistic system compared to TMA-L-Hyp or a CP single system. Several primary factors that might influence the separation were investigated, including CP concentration, TMA-L-Hyp concentration, buffer pH, types and concentrations of organic modifier, applied voltage, and capillary temperature. The best results were obtained with a 40 mM borax buffer (pH 7.6) containing 30 mM TMA-L-Hyp, 80 mM CP, and 20% (v/v) methanol, while the applied voltage and temperature were set at 20 kV and 20°C, respectively. Chirality 27:598-604, 2015.
- Xu, Guangfu,Du, Yingxiang,Du, Fan,Chen, Jiaquan,Yu, Tao,Zhang, Qi,Zhang, Jinjing,Du, Shuaijing,Feng, Zijie
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supporting information
p. 598 - 604
(2015/08/25)
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- Uridine, thymidine and inosine used as chiral stationary phases in HPLC
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In this paper, we present the first enantioseparations research using thymidine, uridine and inosine as chiral stationary phase bonded to silica gel via 3-(triethoxysilyl)propyl isocyanate in HPLC. Thymidine and uridine chiral stationary phases possess enantioseparation selectivity for alcohols, amines, ketones and carboxylic acids to some degree in normal-phase and reversed-phase mode. This work indicates that nucleoside or deoxynucleoside can be useful for the separation of enantiomers in the liquid phase as a new kind of chiral stationary phase.
- Zhang, Mei,Zi, Min,Wang, Bang-Jin,Yuan, Li-Ming
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p. 2226 - 2228
(2014/06/09)
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- Combined use of ionic liquid and hydroxypropyl-β-cyclodextrin for the enantioseparation of ten drugs by capillary electrophoresis
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In the present study, hydroxypropyl-β-cyclodextrin and an ionic liquid (1-ethyl-3-methylimidazolium-l-lactate) were used as additives in capillary electrophoresis for the enantioseparation of 10 analytes, including ofloxacin, propranolol hydrochloride, dioxopromethazine hydrochloride, isoprenaline hydrochloride, chlorpheniramine maleate, liarozole, tropicamide, amlodipine benzenesulfonate, brompheniramine maleate, and homatropine methylbromide. The effects of ionic liquid concentrations, salt effect, cations, and anions of ionic liquids on enantioseparation were investigated and the results proved that there was a synergistic effect between hydroxypropyl-β-cyclodextrin and the ionic liquid, and the cationic part of the ionic liquid played an important role in the increased resolution. With the developed dual system, all the enantiomers of 10 analytes were well separated in resolutions of 5.35, 1.76, 1.85, 2.48, 2.88, 1.43, 5.45, 4.35, 2.76, and 2.98, respectively. In addition, the proposed method was applied to the determination of the enantiomeric purity of S-ofloxacin after validation of the method in terms of selectivity, repeatability, linearity range, accuracy, precision, limit of detection (LOD), and limit of quality (LOQ). Chirality 25:409-414, 2013.
- Cui, Yan,Ma, Xiaowei,Zhao, Min,Jiang, Zhen,Xu, Shuying,Guo, Xingjie
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p. 409 - 414
(2013/07/26)
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- Organocatalytic enantioselective synthesis of β-blockers: (S)-propranolol and (S)-naftopidil
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An efficient enantioselective synthesis of β-adrenergic blockers (S)-propranolol and (S)-naftopidil with >98% ee using an l-proline-catalyzed α-aminoxylation of an aldehyde as a key step is described.
- Panchgalle, Sharad P.,Gore, Rohitkumar G.,Chavan, Subhash P.,Kalkote, Uttam R.
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experimental part
p. 1767 - 1770
(2009/12/28)
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- Cyclic sulfites, key intermediates in synthesis of 1-alkylamino-3-aryloxy-2-propanols from glycidol
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A number of 3-aryloxypropanedioles were obtained by treating glycidol with phenols. The latter with thionyl chloride afforded 4-aryloxymethyl-1,3,2-dioxathiolane 2-oxides. These compounds were also obtained from 4-chloromethyl-1,3,2-dioxathiolane 2-oxides by substitution aryloxy group for chlorine. The cyclic sulfides synthesized are universal intermediates in the synthesis of chiral aryloxypropanolamines among which are known β-adrenoblockaders, cardiovascular drugs. From (S)-glycidol, (S)-alprenolol, (S)-propanolol, and (S)-thymolol were synthesized.
- Bredikhina,Savel'ev,Bredikhin
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p. 213 - 219
(2007/10/03)
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- New approach to nonracemic 1-alkylamino-3-aryloxypropan-2-ols belonging to β-blockers via cyclic sulfites
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Nonracemic β-blockers, viz., (S)-propranolol and (S)-timolol, were prepared from (S)-glycidol in three steps consisting in the reaction with SOCl2 followed by the reaction of the resulting (4S)-4-chloromethyl-2-oxo-1,3,2-dioxathiolanes with the corresponding phenol and the final cleavage of (4R)-aryloxymethyl sulfites under the action of amines in DMF.
- Bredikhina,Pashagin,Savel'ev,Bredikhin
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p. 436 - 439
(2007/10/03)
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- Process for the preparation of 3-amino-2-hydroxy-1-propyl ethers
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PCT No. PCT/JP97/03220 Sec. 371 Date Apr. 28, 1999 Sec. 102(e) Date Apr. 28, 1999 PCT Filed Sep. 12, 1997 PCT Pub. No. WO98/12171 PCT Pub. Date Mar. 26, 1998A process for preparation of 3-amino-2-hydroxy-1-propyl ether of the formula wherein R1 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic ring, R2 and R3 are the same or different hydrogen atom, a substituted or unsubstituted alkyl, or may form a ring together with an adjacent nitrogen atom, which ring may be interrupted with nitrogen atom, oxygen atom or sulfur atom, which is characterized in reacting an epoxy compound of the formula wherein X is halogen, in the presence of a fluoride salt, with an alcohol and then reacting an amine. According to the above method, an intermediates for synthesis of medicines is obtained in good yield and highly optical purity.
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- CsF in organic synthesis. Regioselective nucleophilic reactions of phenols with oxiranes leading to enantiopure β-blockers
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The two modes of the paths in the reaction of oxiranes with phenols are completely controlled by CsF. Glycidyl nosylate undergoes exclusive substitution at the C1 position whereas the ring-opening (C-3 attack) occurs with epichlorohydrin, glycidol, and 1,2-epoxyalkanes. These reactions provide convenient access to enantiopure β-blockers.
- Kitaori, Kazuhiro,Furukawa, Yoshiro,Yoshimoto, Hiroshi,Otera, Junzo
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p. 14381 - 14390
(2007/10/03)
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- Synthesis, stereoselective enzymatic hydrolysis, and skin permeation of diastereomeric propranolol ester prodrugs
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Four diastereomeric propranolol ester prodrugs (1S2S, 1S2R, IR2S, 1R2R) were synthesized by treating pure R- and S-propranolol hydrochloride with pure enantiomers R- and S-phenylbutyryl chloride. A HPLC technique using α- 1 acid glycoprotein (chiral AGP) column was developed to study the racemization of propranolol enantiomers during synthesis and hydrolysis studies. A reversed phase HPLC method was also developed to simultaneously analyze propranolol and the ester prodrug. Hydrolysis of these esters was studied in different rat tissue homogenates, i.e., liver, intestine, plasma, skin, brain, and pure plasma cholinesterases, i.e., butyryl cholinesterase (EC 3.1.1.8) and acetyl cholinesterase (EC 3.1.1.7). In vitro percutaneous permeation studies across full thickness shaved rat skin were performed using standard side-by-side diffusion cells at 37 °C. The disappearance of the diastereomeric ester prodrugs in rat tissue homogenates followed apparent first-order kinetics and was stereoselective. The ratio of brain to plasma hydrolytic rate constants are 27.8, 5.58, 6.07, and 2.97 for 1S2S, 1R2R, 1R2S, and 1S2R esters, respectively. Hydrolysis of all four diastereomeric ester prodrugs was faster by acetyl cholinesterase than butyryl cholinesterase and is stereoselective. The permeability coefficients [K(p) x 103 (cm h-1)] are 1.40 ± 0.30, 1.41 ± 0.27, 42.20 ± 1.24, 29.26 ± 3.41, 16.27 ± 3.12, 12.99 ± 2.84 for (R)-propranolol, (S)-propranolol, 1S2S, 1R2S, 1S2R, and 1R2R ester prodrugs, respectively. The results indicate that the 1R2S diastereomeric ester prodrug of propranolol shows greatest stability in liver and intestinal tissues while it exhibits fairly rapid conversion in plasma. The results also suggest the configuration on the second chiral carbon atom to be the determinant in the rate of hydrolysis of all the diastereomeric prodrugs in all biological media examined. The K(p) of all four prodrugs markedly increased compared to that of the parent drug, with 1S2S showing a 30-fold increase in skin permeability, the highest among all four prodrugs.
- Udata, Chandrasekhar,Tirucherai, Giridhar,Mitra, Ashim K.
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p. 544 - 550
(2007/10/03)
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- Aminoalcohols, III: Preparation of Enantiomerically Pure Pharmacologically Active N-Substituted β-Aminoalcohols
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A synthesis of N-substituted β-aminoalcohols is described starting from enantiomerically pure O-MBF- or O-MBE-protected β-aminoalcohols which can be prepared via LiAlH4 reduction of O-protected cyanohydrines. - Keywords: 1,2-Amino-alcohols, enantiomerically pure; N-Alkylation; Clorprenaline; Propranolol; Midodrine
- Noe, C. R.,Knollmueller, M.,Gaertner, P.,Fleischhacker, W.,Katikarides, E.
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p. 557 - 564
(2007/10/02)
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- Efficient asymmetric hydrogenation of α-amino ketone derivatives. A highly enantioselective synthesis of phenylephrine, levamisole, carnitine and propranolol
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The complexes of pyrrolidine bisphosphine ligands (CPMs) with rhodium (I) were found to be efficient catalysts for asymmetric hydrogenation of α-amino ketone hydrochloride derivatives. Utilizing this methodology, we have developed efficient asymmetric syntheses of the optically active β-amino alcohols, phenylephrine, levamisole, carnitine and propranolol.
- Sukuraba,Takahashi,Takeda,Achiwa
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p. 738 - 747
(2007/10/02)
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- LIPASE-CATALYZED IRREVERSIBLE TRANSESTERIFICATION USING ENOL ESTERS: XAD-8 IMMOBILIZED LIPOPROTEIN LIPASE-CATALYZED RESOLUTION OF SECONDARY ALCOHOLS
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Procedures for preparation of XAD-8 immobilized lipoprotein lipase and the resolution of secondary alcohols of synthetic value in organic solvents using this immobilized enzyme have been developed.
- Hsu, Shu-Hui,Wu, Shihn-Sheng,Wang, Yi-Fong,Wong, Chi-Huey
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p. 6403 - 6406
(2007/10/02)
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- HIGHLY EFFICIENT LIPASE-CATALYZED ASYMMETRIC SYNTHESIS OF CHIRAL GLYCEROL DERIVATIVES LEADING TO PRACTICAL SYNTHESIS OF (S)-PROPRANOLOL
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Efficient asymmetric synthesis of chiral glycerol derivatives was realized by lipase-catalyzed reaction in organic medium and its application for synthesis of (S)-propranolol was demostrated.
- Terao, Yoshiyasu,Murata, Masakazu,Achiwa, Kazuo,Nishio, Toshiyuki,Akamtsu, Minoru,Kamimura, Minoru
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p. 5173 - 5176
(2007/10/02)
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