- In vitro studies of dna damage caused by tricyclic antidepressants: A role of peroxidase in the side effects of the drugs
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Studies show that tricyclic antidepressants prescribed for migraines, anxiety, and child enuresis have numerous adverse effects in living cells. One of the undesired outcomes observed under treatment with these drugs is DNA damage. However, the mechanisms underlying damage have yet to be elucidated. We performed in vitro studies of the DNA damage caused by four tricyclic antidepressants: imipramine, amitriptyline, opipramol, and protriptyline. We focused particularly on the DNA damage aided by peroxidases. As a model of a peroxidase, we used horseradish peroxidase (HRP). At pH 7, reactions of HRP with excess hydrogen peroxide and imipramine yielded an intense purple color and a broad absorption spectrum with the maximum intensity at 522 nm. Reactions performed between DNA and imipramine in the presence of H2O 2 and HRP resulted in the disappearance of the DNA band. In the case of the other three drugs, this effect was not observed. Extraction of the DNA from the reaction mixture indicated that DNA is degraded in the reaction between imipramine and H2O2 catalyzed by HRP. The final product of imipramine oxidation was identified as iminodibenzyl. We hypothesize that the damage to DNA was caused by an imipramine reactive intermediate.
- Korobkova, Ekaterina A.,Ng, William,Venkatratnam, Abhishek,Williams, Alicia K.,Nizamova, Madina,Azar, Nikolay
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- Kinetics and thermodynamic parameters of the thermal decomposition of imipramine hydrochloride and trimipramine maleate
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Thermal decomposition of imipramine hydrochloride and trimipramine maleate has been investigated isothermally and nonisothermally. The kinetic parameters, namely the activation energy Ea and the Arrhenius preexponential term A, were calculated. Applying the theory of activated complex to the process of decomposition one calculated ΔS≠, ΔH≠, and ΔG≠ for the reaction. The values of Ea as well as the thermodynamic functions did not vary significantly with temperature of the reaction whereas the preexponential term showed a significant dependence on the reaction temperature. Both imipramine hydrochloride and trimipramine maleate showed two main steps of decomposition. Each step proved to be a first-order reaction. The rate constant was calculated for each step, and the results were analyzed statistically.
- Abu-Eittah, Rafie H.,Kamel, Laila T.
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- Iron-Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines
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This manuscript details the development of a general and mild protocol for the α-C-H cyanation of tertiary amines and its application in late-stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates and complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles and ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for α-C-H cyanation frequently occur via free radical mechanisms and are thus fundamentally limited in their functional group tolerance. In contrast, the presented catalyst system tolerates functional groups that typically react with free radicals, suggesting an alternative reaction pathway. All components of the described catalyst system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.
- Yilmaz, Ozgur,Dengiz, Cagatay,Emmert, Marion H.
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supporting information
p. 2489 - 2498
(2021/02/06)
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- Photo-catalytic preparation method of bibenzyl compounds
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The invention relates to a preparation method of bibenzyl compounds. A compound represented by a formula (A) and a compound represented by a formula (C) carry out reactions under the action of an organic tungsten catalyst and an alkali in the presence of light to generate bibenzyl compounds represented by the formula (B). The method is simple and is easy to operate. The yield is high, and the application range is wide. Moreover, the invention also provides an application of a tungsten complex in organic chemical reactions as a photocatalyst.
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Paragraph 0072-0075
(2020/02/27)
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- Synthesis method of iminodibenzyl
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The invention relates to the field of drug intermediate synthesis, in particular to a synthesis method of iminodibenzyl, which mainly comprises two steps: a reduction reaction and a cyclization reaction. The yield can be improved to 88%-92% through fine control of the reduction reaction and the cyclization reaction, and the synthesis method has great industrial significance and is worthy of further popularization.
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Paragraph 0006; 0016; 0018-0019; 0020-0027
(2020/07/02)
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- Combined KOH/BEt3Catalyst for Selective Deaminative Hydroboration of Aromatic Carboxamides for Construction of Luminophores
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The selective catalytic C-N bond cleavage of amides into value-added amine products is a desirable but challenging transformation. Molecules containing iminodibenzyl motifs are prevalent in pharmaceutical molecules and functional materials. Here we established a combined KOH/BEt3 catalyst for deaminative hydroboration of acyl-iminodibenzyl derivatives, including nonheterocyclic carboxamides, to the corresponding amines. This novel transition-metal-free methodology was also applied to the construction of Clomipramine and luminophores.
- Li, Jinshan,Wang, Jiali,Yang, Jianguo,Yao, Wubing,Zhong, Aiguo
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supporting information
p. 8086 - 8090
(2020/11/03)
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- Preparation method of imino-adenine intermediate and derivative thereof
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The invention provides a preparation method of imino intermediate dihydro-5H-dibenzo [b, f] azepine. The adopted reaction substrates are 2-bromo-benzoyl chloride, aniline and triethylamine, and the dihydro-5H-dibenzo [b, f] azepine is prepared by a one-step method under a catalytic system of cuprous iodide. The invention further discloses a dihydro-5H-dibenzo [b, f] azepine derivative prepared bythe preparation method. The reaction overcomes the defects of lengthy preparation process, high cost, long consumed time and low yield in the traditional method; a one-step reaction is conducted to obtain the intermediate dihydro-5H-dibenzo [b, f] azepine and the derivative thereof, the yield of the target product is as high as 45-55%, the preparation route of the dihydro-5H-dibenzo [b, f] azepineis greatly shortened, the preparation effect of the dihydro-5H-dibenzo [b, f] azepine is improved, and the method has a wide industrial prospect.
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Paragraph 0038-0045
(2020/07/13)
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- Hydride-catalyzed selectively reductive cleavage of unactivated tertiary amides using hydrosilane
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The first hydride-catalyzed reductive cleavage of various unactivated tertiary amides, including the biologically active aryl-phenazine carboxamides and the challenging non-heterocyclic carbonyl functions, using low-cost hydrosilane as a reducing reagent has been developed. The novel catalyst system exhibits high efficiency and exclusive selectivity, providing the desired amines in useful to excellent yields under mild conditions. Overall, this transition metal-free process may offer a versatile alternative to currently employed expensive reducing reagents, high-pressure hydrogen or metal systems for the selective reductive cleavage of amides.
- Yao, Wubing,Li, Rongrong,Yang, Jianguo,Hao, Feiyue
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p. 3874 - 3878
(2019/08/07)
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- Photoredox-Catalyzed Cα-H Cyanation of Unactivated Secondary and Tertiary Aliphatic Amines: Late-Stage Functionalization and Mechanistic Studies
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This paper describes the development and mechanistic studies of a general, high-yielding amine Cα-H cyanation protocol via photoredox catalysis. Inexpensive NaCN is employed as the cyanide source and air is the external oxidant, resulting in mild and highly functional group tolerant conditions. Notably, efficient Cα-H cyanations of secondary and tertiary aliphatic amines and of complex, biologically active compounds (drugs) can be performed using the established methodology. Mechanistic studies suggest that the carboxylic acid additive has three effects: formation of a stabilizing hemiaminal intermediate, prevention of catalyst decomposition by protonating the substrate, and modulation of fluorescence quenching of the photoexcited catalyst species.
- Yilmaz, Ozgur,Oderinde, Martins S.,Emmert, Marion H.
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p. 11089 - 11100
(2018/09/12)
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- Method for preparing medicine and medicine intermediate by continuous solid-liquid-gas three-phase reaction
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The invention provides a method for preparing meropenem or a 10,11-dihydro-5H-dibenzo[b, f] azepine by a continuous solid-liquid-gas three-phase reaction. A reactant in which acatalyst is dissolved ispumped into a microchannel reactor by using a diaphragm pump, and the hydrogen is bubbled into the reactor by using the pressure of a steel cylinder. The method uses the microchannel reactor to realize the continuous production of the meropenem or the 10,11-dihydro-5H-dibenzo[b, f] azepine. The technical effects of short reaction time, thorough reaction and high product yield are achieved.
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Paragraph 0043; 0047
(2018/07/30)
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- Method for catalytic synthesis of iminodibenzyl
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The invention discloses a preparation method of iminodibenzyl. The method utilizes 2, 2-diaminobibenzyl as a raw material to realize catalytic synthesis of iminodibenzyl. The preparation method comprises filling a fixed bed reactor with a H3PO4/SiO2. Al2O3 catalyst, carrying out heating to 280 to 370 DEG C, introducing high temperature water vapor into the heated liquid 2, 2-diaminobibenzyl raw material so that bubbles are produced at the bottom and bring out the raw material, introducing water vapor mixed gas with the raw material into and through a fixed bed reaction pipe with the H3PO4/SiO2. Al2O3 catalyst so that the raw material undergoes a deamination and loop closing reaction in the catalyst bed to produce a desired product, and precipitating the vapor-carried desired product in a solid form in a condenser pipe. The preparation method has an iminodibenzyl single-pass yield of 100%, realizes continuous synthesis for 3 months without replacement of a catalyst and has an iminodibenzyl yield of 98% or more.
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Paragraph 0019; 0020
(2017/06/02)
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- Alkene Hydrogenations by Soluble Iron Nanocluster Catalysts
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The replacement of noble metal technologies and the realization of new reactivities with earth-abundant metals is at the heart of sustainable synthesis. Alkene hydrogenations have so far been most effectively performed by noble metal catalysts. This study reports an iron-catalyzed hydrogenation protocol for tri- and tetra-substituted alkenes of unprecedented activity and scope under mild conditions (1–4 bar H2, 20 °C). Instructive snapshots at the interface of homogeneous and heterogeneous iron catalysis were recorded by the isolation of novel Fe nanocluster architectures that act as catalyst reservoirs and soluble seeds of particle growth.
- Gieshoff, Tim N.,Chakraborty, Uttam,Villa, Matteo,Jacobi von Wangelin, Axel
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supporting information
p. 3585 - 3589
(2017/03/21)
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- A disubstituted amide derivatives decarbonylation hydrogenation green new method (by machine translation)
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The invention relates to a high efficiency, high selectivity of the disubstituted amide derivatives of decarbonylation hydrogenation reaction green new method. For the first time to the metallic compound triethylborane as catalyst, under mild conditions can be conveniently catalytic N, N - di-aryl substituted amide and its derivative and cheap and easy to obtain organic silicon reagent selective preparation of secondary organic amine product. Compared with the traditional method, the new method generally has the wide substrate universality, functional group compatibility outstanding, simple operation and the like. For the first time in order to realize the organic silicon reagent as reducing agent and amide compounds decarbonylation hydrogenation reaction, is the reduction of amides and derivatives thereof, in particular the organic light-emitting diodes (OLEDs) material unit - diaryl amine compound of the laboratory preparation or industrial production provides a brand-new "green" response strategies. (by machine translation)
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Paragraph 0034; 0035; 0036; 0037
(2018/02/04)
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- N-heterocyclic silylene (NHSi) rhodium and iridium complexes: Synthesis, structure, reactivity, and catalytic ability
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Reaction of the zwitterionic N-heterocyclic silylene (NHSi) 1 L′Si: (L′≤[HC(CMeNAr)(C(CH2)NAr)], Ar≤2,6-iPr2C6H3) with HCl at low temperatures affords the kinetically stable 1,4-addition product of 1, LSiCl (L≤[HC(CMeNAr)2], Ar≤2,6-iPr2C6H3) (9a), which upon reaction with [Rh(Cl)cod]2 and [Ir(Cl)cod]2 (cod≤1,5-cyclooctadiene) selectively affords the NHSi complexes [L(Cl)Si:→Rh(Cl)cod] (10a) and [L(Cl)Si:→Ir(Cl)cod] (10b), respectively. The latter were employed as pre-catalysts in the catalytic reduction of amides in the presence of silanes. Remarkably, they show strikingly different activities and selectivities. While complex 10a yields selectively the C-O cleavage product, 10b affords both cleavage products (C-O and C-N). Moreover, the total conversion of the catalytic amide reduction with 10b is significantly higher than the conversion with a benchmark system [Ir(Cl)cod]2 highlighting the enhanced catalytic activity afforded by the coordination of the NHSi ligand. Introducing the hydride source Li[HBEt3] into the catalytic reactions retards the catalyst performance due to a competitive decomposition pathway. This appears to occur via a H-shift onto the cod ligand with concomitant liberation of cyclooctene, which is also presented. The different reactivity of 10a and 10b towards nucleophiles such as MeLi is also discussed. The reaction of 10a with MeLi affords an intractable array of products, while the reaction of 10b with one equivalent of MeLi selectively affords [L(Cl)Si:→Ir(CH3)cod] (14) with selective methylation at the Ir centre. The analogous reaction with two equivalents of 10b affords the double methylated product [L(CH3)Si:→Ir(CH3)cod] (15).
- Stoelzel, Miriam,Praesang, Carsten,Blom, Burgert,Driess, Matthias
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p. 1163 - 1170
(2013/10/22)
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- Friedel-crafts chemistry. Part 39. unprecedented facile route to the synthesis of benzo[b][1]benzazepines via intramolecular friedel-crafts cyclialkylations
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A series of six pharmaceutically promising 5,6-dihydro-11H-benzo[b][1] benzazepine derivatives (1c-h) were cleanly prepared by Friedel-Crafts cyclialkylations of nitrogen-containing alkanols in the presence of AlCl3, 85% H2SO4 or polyphosphoric acid catalysts. The precursor alkanols (13a-f) were readily prepared by reaction of two synthesized carboxylic acid esters (12a, b) with different Grignard reagents. Also, two dibenzo[b,f]azepinones (15a, b) were prepared by Friedel-Crafts cycliacylation and reduced to the corresponding 5,6-dihydro-11H-benzo[b][1]benzazepines (1a, b). Overall, this approach allows easy and efficient access to polytricyclic amines from easily synthesized alkanols or cycloketones. A plausible carbocation mechanism is proposed to account for the results.
- El-Aal, Hassan A. K. Abd,Khalaf, Ali A.
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p. 635 - 645
(2013/07/26)
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- Reductive cleavage of amides to alcohols and amines catalyzed by well-defined bimetallic molybdenum complexes
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Triple bonds do it! The molybdenum-catalyzed Ci-N bond cleavage of organic amides with hydrosilanes to produce alcohols and amines has been investigated. This work complements previously established protocols that lead to the cleavage of the Ci-O bond. Modified triply bonded dimolybdenum(III) alkoxides have been found to be crucial for tuning the selectivity to Ci-N bond cleavage (see figure). Copyright
- Krackl, Sebastian,Someya, Chika I.,Enthaler, Stephan
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supporting information
p. 15267 - 15271
(2013/01/15)
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- Reactive metabolites of desipramine and clomipramine: The kinetics of formation and reactivity with DNA
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Tricyclic antidepressants (TCAs), along with phenothyazines and some industrial chemicals, are shown to react with enzymes that exhibit peroxidase activity. These reactions result in the formation of reactive intermediates having unpaired electrons. The peroxidase oxidation and reactivity of two TCAs, desipramine and clomipramine, were investigated. As a model of peroxidase, horseradish peroxidase (HRP) was employed. The products of the peroxidase catalyzed oxidation of desipramine and clomipramine were identified as N-dealkylated compounds iminodibenzyl and 3-chloroiminodibenzyl using the GC/MS technique. Both drugs formed broad UV/vis absorption spectra in the presence of HRP and H2O2, indicating the formation of a radical cations - reactive intermediate of the oxidation reaction. The dynamics of the formation of the desipramine intermediate was studied using UV/vis spectroscopy. The extinction coefficient was measured for the reactive intermediate, 7.80 × 103 M-1 cm-1, as well as the apparent Michaelis-Menten and catalytic constants, 4.4 mM and 2.3 s-1, respectively. Both desipramine and clomipramine degraded DNA in the presence of HRP/H2O2, as was revealed by agarose gel electrophoresis and PCI extraction. Manipulating the kinetic parameters of drug's radical formation and determining the extent of degradation to biomolecules could be potentially used for designing effective agents exhibiting specific reactivity.
- Korobkova, Ekaterina A.,Nemeth, John,Cadougan, Mikeisha,Venkatratnam, Abhishek,Bassit, Mohanram,Azar, Nikolay
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scheme or table
p. 340 - 345
(2012/03/08)
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- Synthesis of new dibenzo[b,f]azepine derivatives
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This work is focused on synthesis and chemical characterization of new polycyclic compounds having dibenzo[b,f] azepine and 10,11-dihydrodibenzo[b,f] azepine moieties. We report the synthesis of four new compounds, obtained by reacting 5H-dibenzo[b,f]azepine-5-carbonyl chloride and 10,11-dihydro-5H- dibenzo[b,f]azepine-5-carbonyl chloride with 1-phenylpiperazine, and pyrrolidine, respectively. The newly synthesized compounds were characterized using chromatographic and spectroscopic methods (HPLC-UV-VIS 1H-NMR, 13C-NMR, mass spectrometry by ESI technique).
- Balaure, Paul Catalin,Costea, Ion,Iordache, Florin,Draghici, Constantin,Enache, Cristian
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scheme or table
p. 935 - 942
(2011/06/21)
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- Novel derivatives and analogues of galanthamin
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New compounds of general formula I 1
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- Reduction of diaryl alkenes by hypophosphorous acid-iodine in acetic acid
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A mixture of 50% aqueous H3PO2 and I2 (in catalytic amount) in HOAc efficiently reduces aryl alkenes to the corresponding alkanes in high yield. Addition of acetic anhydride to the medium results in ring-acetylation (or N-acetylation in the case of amines). H3PO2 costs only one-fifth as much as hydriodic acid on a mole basis and one mole of H3PO2 produces four moles of HI, resulting in a 20-fold cost advantage for H3PO2/I2 over aqueous HI as a source of HI.
- Fry, Albert J.,Allukian, Myron,Williams, Allison D.
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p. 4411 - 4415
(2007/10/03)
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- The prop-2-ynyloxy carbonyl function (POC): A new amino-protecting group removable from sulfur-containing peptides by ultrasonic irradiation with tetrathiomolybdate under mild and neutral conditions
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The prop-2-ynyloxy carbonyl function (POC) which can be cleaved under mild and neutral conditions in the presence of benzyltriethylammonium tetrathiomolybdate has been developed as a new protecting group for amines.
- Sinha, Surajit,Ilankumaran, Palanichamy,Chandrasekaran, Srinivasan
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p. 771 - 774
(2007/10/03)
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- Site Selectivity and Regioselectivity of Nitrile Oxide Cycloadditions to N,N-Diarylaminoallenes
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N,N-Diarylaminoallenes were synthesized by isomerisation of the corresponding propargyl derivatives and submitted to reaction with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide. 5-Diarylamino-4-methylene-4,5-dihydroisoxazoles were formed with full site selectivity and regioselectivity. These cycloadducts were susceptible to nitrile oxide cycloaddition onto the exocyclic double bond as well as to acid-promoted amino-Claisen rearrangement.
- Broggini, Gianluigi,Molteni, Giorgio,Zecchi, Gaetano
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p. 1263 - 1278
(2007/10/02)
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- Metabolism of imipramine by microorganisms
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The microbial metabolism of imipramine was studied using selected fungal organisms. The major microbial metabolites were isolated, and their structures were established by spectroscopic analyses (particularly 13C-NMR) and by comparison with authentic samples. The microbial metabolites identified included 2-hydroxyimipramine, 10-hydroxyimipramine, iminodibenzyl, imipramine-N-oxide, and desipramine; these metabolites also have been found in mammalian metabolism studies.
- Hufford,Capiton,Clark,Baker
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p. 151 - 155
(2007/10/02)
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