26328-11-0Relevant articles and documents
Enantioselective hydrogenation of dehydro-amino acid derivatives using pindophos-rhodium as chiral catalyst
Kreuzfeld, Hans-Joern,Schmidt, Ute,Doebler, Christian,Krause, Hans Walter
, p. 1011 - 1018 (1996)
The enantiomers of PINDOPHOS, the aminophosphine phosphinite derivative of the commercial β-blocker Pindolol, were prepared and used as ligands in the rhodium catalyzed asymmetric hydrogenation of non-proteinogenic amino acid precursors. The isolated (R)- and (S)-configured rhodium complexes are highly active catalysts leading to (L)- or (D)-amino acids. Enantiomeric excesses between 92 and 95% ee could be realized. The newly obtained amino acid derivatives were fully characterized by NMR spectroscopy.
Chemoenzymatic synthesis of (S)-Pindolol using lipases
Lima, Gledson Vieira,da Silva, Marcos Reinaldo,de Sousa Fonseca, Thiago,de Lima, Leandro Bezerra,de Oliveira, Maria da Concei??o Ferreira,de Lemos, Telma Leda Gomes,Zampieri, Davila,dos Santos, Jose Cleiton Sousa,Rios, Nathalia Saraiva,Gon?alves, Luciana Rocha Barros,Molinari, Francesco,de Mattos, Marcos Carlos
, p. 7 - 14 (2017)
A straightforward chemoenzymatic synthesis of (S)-Pindolol has been developed. The key step involved the enzymatic kinetic resolution of rac-2-acetoxy-1-(1H-indol-4-yloxy)-3-chloropropane with lipase from Pseudomonas fluorescens via hydrolytic process to obtain enantiomerically enriched halohydrin (2S)-1-(1H-indol-4-yloxy)-3-chloro-2-propanol (96% ee) and (2R)-2-acetoxy-1-(1H-indol-4-yloxy)-3-chloropropane (97% ee). The latter was subjected to a hydrolysis reaction catalyzed by Candida rugosa leading to (2R)-1-(1H-indol-4-yloxy)-3-chloro-2-propanol (97% ee), followed by a reaction with isopropylamine, producing (S)-Pindolol (97% ee) in quantitative yield.
Synthesis and crystal structure of (S)-pindolol
Bredikhin, Alexander A.,Bredikhina, Zemfira A.,Kurenkov, Alexey V.,Krivolapov, Dmitry B.
, p. 442 - 446 (2017)
Racemic 3-(4-indolyloxy)-1,2-propanediol 2 has been effectively resolved into (S)- and (R)-enantiomers by a preferential crystallization procedure. Non-racemic (S)-2 was converted into (S)-4-(2,3-epoxypropoxy)-1H-indole (S)-4 via a Mitsunobu reaction and then into (S)-pindolol (S)-1. The crystalline (S)-1 was studied by single crystal X-ray diffraction. A large number of symmetry independent molecules (Z' = 6) led to a weakening of the system of strong intermolecular hydrogen bonds, which combined with a loose packing (PI = 64.6%), may be the cause of the abnormally low melting point of (S)-1 as compared with rac-1.
Syntheses of (S)-(-)-Pindolol and -(R)-(-)-Pindolol Utilizing a Lanthanum-Lithium-(R)-BINOL ((R)-LLB) Catalyzed Nitroaldol Reaction
Sasai, Hiroaki,Yamada, Yoichi M. A.,Suzuki, Takeyuki,Shibasaki, Masakatsu
, p. 12313 - 12318 (1994)
An efficient synthesis of (-)-pindolol, an effective β-blocker, has been achieved utilizing a lanthanum-lithium-(R)-BINOL ((R)-LLB) catalyzed nitroaldol reaction as a key step.This methodology was applicable to a synthesis of (13)C-labeled (-)-pindolol, which would be useful as a biological tool for tracing the metabolism of β-blocker and 5-HT1A receptor antagonist.The mechanistic aspects of the LLB catalyzed nitroaldol reaction are also discussed.
Preparation of a novel hydroxypropyl-γ-cyclodextrin functionalized monolith for separation of chiral drugs in capillary electrochromatography
Deng, Miaoduo,Xue, Mengyao,Liu, Yanru,Zhao, Min
, p. 188 - 195 (2021/02/26)
In this study, a novel hydroxypropyl-γ-cyclodextrin (HP-γ-CD) functionalized monolithic capillary column was prepared by one-pot sequential strategy and used for chiral separation in capillary electrochromatography for the first time. In one pot, GMA-HP-γ-CD as functional monomer was allowed to be formed via the ring opening reaction between HP-γ-CD and glycidyl methacrylate (GMA) catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and then copolymerized directly with ethylene dimethacrylate (EDMA) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) in the presence of porogenic solvents via thermally initiated free radical polymerization. The preparation conditions of monoliths were optimized. Enantiomer separations of six chiral drugs including pindolol, clorprenaline, tulobuterol, clenbuterol, propranolol, and tropicamide were achieved on the monolith. Among them, pindolol, clorprenaline, and tropicamide were baseline separated with resolution values of 1.62, 1.73, and 1.55, respectively. The mechanism of enantiomer separation was discussed by comparison of the HP-γ-CD and HP-β-CD functionalized monoliths.
Enantiomeric separation of β-blockers and tryptophan using heparin as stationary and pseudostationary phases in capillary electrophoresis
Liu, Yi,Sombra, Lorena L.,Stege, Patricia W.
, p. 988 - 995 (2018/07/29)
The separation methods of the enantiomers of two β-blockers and tryptophan were studied using capillary electrochromatography with heparin covalently as well as non-covalently, bonded onto the capillary inner wall as stationary phase and electrokinetic chromatography with heparin as pseudostationary phase. In the case of heparin, used as a stationary phase, the method was unable to resolve enantiomers in both cases β-blockers and tryptophan. On the other hand, when heparin was used as a pseudostationary phase, the resolution of the enantiomers was obtained only with 3-aminopropyltriethoxysilane which were immobilised onto the inner phase of the capillary. The results of this study let us infer that the electrostatic, hydrophobic, and steric interactions were involved in the separation mechanisms. The separation was achieved in less than 10?minutes under the optimized conditions: 30?mM phosphate buffer (pH?2.5) with the adding of 15?mg/mL of heparin at 15°C and 10?kV. The usefulness of heparin as a chiral selector both in electrokinetic chromatography using 3-aminopropyltriethoxysilane attached to the capillary was demonstrated for the first time. The developed method was powerful, sensitive, and fast, and it could be considered an important alternative to conventional methods used for chiral separation.
Enantioselective potential of polysaccharide-based chiral stationary phases in supercritical fluid chromatography
Kucerova, Gabriela,Kalikova, Kveta,Tesarova, Eva
supporting information, p. 239 - 246 (2017/05/29)
The enantioselective potential of two polysaccharide-based chiral stationary phases for analysis of chiral structurally diverse biologically active compounds was evaluated in supercritical fluid chromatography using a set of 52 analytes. The chiral selectors immobilized on 2.5?μm silica particles were tris-(3,5-dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of the polysaccharide backbone, different organic modifiers, and different mobile phase additives on retention and enantioseparation was monitored. Conditions for fast baseline enantioseparation were found for the majority of the compounds. The success rate of baseline and partial enantioseparation with cellulose-based chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose-based chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6% of partial enantioseparations of the tested compounds. The best results on cellulose-based chiral stationary phase were achieved particularly with propane-2-ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO2, respectively. Methanol and basic additive isopropylamine were preferred on amylose-based chiral stationary phase. The complementary enantioselectivity of the cellulose- and amylose-based chiral stationary phases allows separation of the majority of the tested structurally different compounds. Separation systems were found to be directly applicable for analyses of biologically active compounds of interest.
Application of cyclam-capped β-cyclodextrin-bonded silica particles as a chiral stationary phase in capillary electrochromatography for enantiomeric separations
Gong, Yinhan,Lee, Hian Kee
, p. 1348 - 1354 (2007/10/03)
Two novel types of substituted cyclam-capped β-cyclodextrin (β-CD)-bonded silica particles have been prepared and used as chiral stationary phases in capillary electrochromatography (CEC). The two stationary phases have a chiral selector with three recognition sites: β-CD, cyclam, and the latter's sidearm. They exhibit excellent enantioselectivities in CEC for a wide range of compounds as a result of the cooperative functioning of the anchored β-CD and cyclam. After inclusion of the metal ion (Ni2+) from the running buffer into the substituted cyclams and their sidearm ligands, the bonded stationary phases become positively charged and can provide extra electrostatic interactions with ionizable solutes and enhance the dipolar interactions with some polar neutral solutes. This enhances the host-guest interaction with some solutes and improves chiral recognition and enantioselectivity. These new types of stationary phases exhibit great potential for fast chiral separations in CEC.
Process for the preparation of 3-amino-2-hydroxy-1-propyl ethers
-
, (2008/06/13)
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.
CsF in organic synthesis. Regioselective nucleophilic reactions of phenols with oxiranes leading to enantiopure β-blockers
Kitaori, Kazuhiro,Furukawa, Yoshiro,Yoshimoto, Hiroshi,Otera, Junzo
, p. 14381 - 14390 (2007/10/03)
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.
