- Supercritical fluid extraction: A novel method for the resolution of tetramisole
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A new resolution method, based on the selective distribution of enantiomers between a chiral solid and an achiral supercritical fluid phase, is reported. The chiral solid phase is formed from the optically active dicarboxylic acid derivative, (2R,3R)-O,O'-dibenzoyltartaric acid, and the racemic base (tetramisole). A new method is also described for the enrichment of enantiomeric mixtures which have an enantiomeric ratio other than 1:1. This is based on the partial salt formation of the enantiomeric mixture with an achiral substance, which is then followed by supercritical fluid extraction of the free enantiomer. The extract has an enantiomeric composition which is different from the starting mixture. The method is applied to an enantiomeric mixture of tetramisole with hydrochloric acid.
- Keszei, Sandor,Simandi, Bela,Szekely, Edit,Fogassy, Elemer,Sawinsky, Janos,Kemeny, Sandor
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- Effect of ultrasound-assisted crystallization in the diastereomeric salt resolution of tetramisole enantiomers in ternary system with O,O′-dibenzoyl-(2R,3R)-tartaric acid
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The diastereomeric salt resolution of racemic tetramisole was studied using ultrasound irradiation. We examined the effect of power and duration of ultrasonic irradiation on the properties of the crystalline phase formed by ultrasound-assisted crystallization and the result of the whole optical resolution. The results were compared with reference experiment without using ultrasound. The US time (5-30 min) caused higher enantiomeric excess. Although yield was lower continuously high resolving efficiency could have been reached through ultrasound. We had the best results with 4.3 W ultrasound power when resolvability was even higher than the best of reference. Furthermore, we accomplished a deep and thorough examination of the salts that possibly could form in this resolution. One of the four diastereomeric salts, which have been identified by powder X-ray diffraction, FTIR-spectroscopy, and differential scanning calorimetry (DSC) in the ternary system of the two tetramisole enantiomers and the resolving agent, namely the bis[(S)-tetramisole]-dibenzoyl-(R,R)-tartrate salt have been proven the key compound in the resolution process, and presented the highest melting point of 166 °C (dec.) among the four salts. The originally expected diastereomeric bitartrate salts with 1:1 M base:acid ratio [(S)-tetramisole-dibenzoyl-(R,R)-hydrogen-tartrate salt and (R)-tetramisole-dibenzoyl-(R,R)-hydrogen-tartrate salt] and their 'racemic' co-crystal [(RS)-tetramisole-dibenzoyl-(R,R)-hydrogen-tartrate salt] showed somewhat lower melting points (152, 145, and 150 °C, respectively) and their crystallization was also prevented by application of ultrasound. Based on the melting points and enthalpies of fusion measured by DSC, all the binary and ternary phase diagrams have been newly established and calculated in the system with help of classical modelling equations of liquidus curves.
- Szeleczky, Zsolt,Kis-Mihály, Erzsébet,Semsey, Sándor,Pataki, Hajnalka,Bagi, Péter,Pálovics, Emese,Marosi, Gy?rgy,Pokol, Gy?rgy,Fogassy, Elemér,Madarász, János
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- Effect of achiral support on the resolution of tetramisole by supercritical fluid extraction
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The enantiomers of tetramisole were produced by partial diastereomeric salt formation with O,O′-dibenzoyl-(2R,3R)-tartaric acid monohydrate and subsequent supercritical fluid extraction (SFE) of the unreacted enantiomers in the presence of an achiral support. The effect of the activated carbon and Perfil 100 on the efficiency of chiral separation were studied. The kinetics of the process was found to be an important factor affecting enantioselectivity. When the parameters were properly set, much better resolution efficiency (F) and higher enantiomeric purity were achieved than in the equilibrium. The presence of Perfil 100 and activated carbon caused an increase as high as 53 and 84% in F, respectively, compared to that achieved without using any supporting material. Thus during the development of a resolution procedure, beside the proper resolution agent, optimised molar ratio and other parameters, the selection of achiral addict(s) may be also an important point.
- Szekely, Edit,Simandi, Bela,Laszlo, Krisztina,Fogassy, Elemer,Pokol, Gyoergy,Kmecz, Ildiko
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- Total Synthesis of (-)-Xylogranatopyridine B via a Palladium-Catalyzed Oxidative Stannylation of Enones
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We report a total synthesis of the pyridine-containing limonoid alkaloid (-)-xylogranatopyridine B in 11 steps from commercially available dihydrocarvone. The central pyridine ring was assembled by a late-stage fragment coupling approach employing a modified Liebeskind pyridine synthesis. One fragment was prepared by an allyl-palladium catalyzed oxidative enone β-stannylation, in which the key bimetallic β-stannyl palladium enolate intermediate undergoes a β-hydride elimination. This methodology also allowed introduction of alkyl and silyl groups to the β-position of enones.
- Schuppe, Alexander W.,Huang, David,Chen, Yifeng,Newhouse, Timothy R.
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supporting information
p. 2062 - 2066
(2018/02/19)
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- Enantioselective aza-Henry reaction for the synthesis of (S)-levamisole using efficient recyclable chiral Cu(II)-amino alcohol derived complexes
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Chiral Cu(II) complexes were generated in situ by the interaction of aminoalcohol based ligands L1-L6 derived from (1R,2S)-(-)-2-aminodiphenylethanol, (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol, (R or S)-valinol and (S)-2-amino-1,1-diphenylpropan-1-ol with 4-tert-butyl-2,6-diformylphenol and screened for aza-Henry reaction of a variety of aromatic, aliphatic N-tosylaldimine and aromatic N-benzenesulfonamide aldimine in toluene at RT. Excellent enantioselectivity, diastereoselectivity (99%) of β-nitro-N-tosylaldamine with good yield (80%) was achieved in case of complex L2-Cu(II) with low catalyst loading. The enantio-pure aza-Henry product obtained was straightforwardly transformed into the enantioenriched chiral vicinal diamine (ee; 96%) with good yield in successive two steps and was further used for the synthesis of (S)-levamisole (an anthelminthic agent). The catalytic system worked well up to five cycles with retention of enantioselectivity.
- Choudhary, Manoj K.,Tak, Rajkumar,Kureshy, Rukhsana I.,Ansari, Amamudin,Khan, Noor-Ul H.,Abdi, Sayed H.R.,Bajaj, Hari C.
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- Preparation and immunological evaluation of organic acid salts of levamisole
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Four kinds of organic acid salts of levamisole were prepared from levamisole hydrochloride and organic acids (L-ascorbic acid, tartaric acid, citric acid and ferulic acid) by solvent crystallization method, respectively. The salts were characterized by elemental analysis, UVVIS, FTIR, ESI-MS, DSC-TGA, solubility in water, melting point, optical rotation and pH in water. The immunosuppressed mice models were established by intraperitoneal injection of cyclophosphamide to verify and compare the effects of levamisole hydrochloride and organic acid salts of levamisole on immune functions of immunosuppressed mice. The results showed while significantly increasing the contents of serum IgM and IgG and the immune organ indexes in cyclophosphamide-induced immunosuppressed mice, levamisole ferulate and levamisole tartrate presented higher increases in IgG contents and immune organ indexes than other salts did. Thus, it could be concluded that levamisole ferulate and levamisole tartrate were more effective on immune enhancement than other salts.
- Feng, Xiaoling,Yang, Yi,Wang, Jianhua
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p. 634 - 640
(2014/06/09)
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- Oxazoline-based organocatalyst for enantioselective strecker reactions: A protocol for the synthesis of levamisole
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A chiral oxazoline-based or-ganocatalyst has been found to efficiently catalyze asymmetric Strecker reactions of various aromatic and aliphatic N-benzhydrylimines with trime-thylsilyl cyanide (TMSCN) as a cyanide source at -20°C to give α-aminoni-triles in high yield (96%) with excellent chiral induction (up to 98% ee). DFT calculations have been performed to rationalize the enantioselective formation of the product with the organo-catalyst in these reactions. The organo-catalyst has been characterized by single-crystal X-ray diffraction analysis, as well as by other analytical methods. This protocol has been extended to the synthesis of the pharmaceutically important drug molecule levamisole in high yield and with high enantioselectivity.
- Sadhukhan, Arghya,Sahu, Debashis,Ganguly, Bishwajit,Khan, Noor-Ul H.,Kureshy, Rukhsana I.,Abdi, Sayed H.R.,Suresh,Bajaj, Hari C.
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supporting information
p. 14224 - 14232
(2013/11/06)
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- Enantioselective metal-free diamination of styrenes
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Metal-free and asymmetric: The first enantioselective diamination of styrenes simply requires a chiral hypervalent iodine(III) reagent as an oxidant and bismesylimide as a nitrogen source (see scheme, Ms=methanesulfonyl). The reaction proceeds under mild conditions and with high enantiomeric excess.
- Roeben, Caren,Souto, Jose A.,Gonzalez, Yolanda,Lishchynskyi, Anton,Muniz, Kilian
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p. 9478 - 9482
(2011/11/06)
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- Silylation-based kinetic resolution of monofunctional secondary alcohols
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The nucleophilic small molecule catalyst (-)-tetramisole was found to catalyze the kinetic resolution of monofunctional secondary alcohols via enantioselective silylation. Optimization of this new methodology allows for selectivity factors up to 25 utilizing commercially available reagents and mild reaction conditions.
- Sheppard, Cody I.,Taylor, Jessica L.,Wiskur, Sheryl L.
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supporting information; experimental part
p. 3794 - 3797
(2011/10/02)
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- A new facile chemoenzymatic synthesis of levamisole
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An efficient and facile chemoenzymatic synthesis of levamisole by employing lipase-mediated resolution of 3-hydroxy-3-phenylpropanenitrile followed by its conversion to β-amino alcohol as the key intermediate is described.
- Kamal, Ahmed,Khanna, G.B. Ramesh,Krishnaji,Ramu
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p. 613 - 615
(2007/10/03)
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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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- Use of disulfonyl methanes for the control of parasites
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The present invention is directed to the use of disulfonyl methane compounds for the control of parasites in vertebrate animals.
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- 1,5-diphenyl-3-formazancarbonitril parasiticides
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The present invention is directed to the use of 1,5-diaryl-3 -formazancarbonitrile compounds for the control of parasites in vertebrate animals.
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- Optically active 1-oxyethyl-4-phenyl-2-imidazolidones
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A process for the manufacture of 1-(2-alkoxyethyl)-4-phenyl-4-imidazolin-2-ones, 1-(2-alkoxyethyl)-4-phenyl-2-imidazolidones, 1-(2-alkoxyethyl)-4-phenyl-imidazolidine-2-thiones, certain of the corresponding 1-(2-hydroxyethyl) derivatives, and their 3-acylated derivatives, and certain related compounds which are all useful as intermediates in a new process for the manufacture of the anthelmintic levamisole, (-)-2,3,5,6-tetrahydro-6-phenylimidazo-[2,1-b]thiazole, and its derivatives through conventional resolution procedures. The new process also permits the direct manufacture of optically active 1-(2-alkoxyethyl)-4-phenyl-2-imidazolidone and their 3-acylated derivatives, optically active 1-(2-alkoxyethyl)-4-phenylimidazolidine-2-thiones, and levamisole, the levorotatory isomer of tetramisole, using catalytic amounts of a chiral reducing agent, with the elimination of conventional resolution procedures.
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- Pharmaceutical composition and process of treatment
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A process for alleviating proliferative skin diseases such as psoriasis, atopic dermatitis, etc. comprising administering to humans, or domesticated animals, topically and/or systemically a composition comprising a pharmaceutical carrier and at least one active compound selected from the groups, substituted alkyl zanthines, tricyclic antidepressants, organic nitrates, antihypertensives, anti-asthma agents and central nervous system depressants and combinations of certain compounds from specifically named groups of compounds.
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