- Hypervalent iodine oxidation products of papaverine and its microbial metabolites
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(Diacetoxyiodo)benzene (DAIB) oxidizes papaverine to papaveraldine (2) and to 1-hydroxymethyl-6,7-dimethoxyisoquinoline (3), whereas 3'-desmethylpapaverine and 6-dexmethylpapaverine are converted into novel products (4) and (5), respectively.
- Reddy, G. Chandrasekara
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- Metal- And additive-free C-H oxygenation of alkylarenes by visible-light photoredox catalysis
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A metal- and additive-free methodology for the highly selective, photocatalyzed C-H oxygenation of alkylarenes under air to the corresponding carbonyls is presented. The process is catalyzed by an imide-acridinium that forms an extremely strong photooxidant upon visible light irradiation, which is able to activate inert alkylarenes such as toluene. Hence, this is an easy to perform, sustainable and environmentally friendly oxidation that provides valuable carbonyls from abundant, readily available compounds.
- García Manche?o, Olga,Kuhlmann, Jan H.,Pérez-Aguilar, María Carmen,Piekarski, Dariusz G.,Uygur, Mustafa
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supporting information
p. 3392 - 3399
(2021/05/21)
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- Preparation method of papaverine compounds
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The invention relates to a preparation method of papaverine compounds. Specifically, the invention relates to a preparation method of a compound as shown in a formula II, and the preparation method comprises a step of reacting a compound as shown in a formula III in the presence of an oxidizing agent. The method is high in yield, mild in reaction condition and suitable for industrial production.
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Paragraph 0065-0067
(2021/07/21)
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- Development of Pd(OAc)2-catalyzed tandem oxidation of C[sbnd]N, C[sbnd]C, and C(sp3)–H bonds: Concise synthesis of 1-aroylisoquinoline, oxoaporphine, and 8-oxyprotoberberine alkaloids
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A catalytic tandem oxidation of C[sbnd]N, C[sbnd]C, and C(sp3)–H bonds is developed. This tandem oxidation is applied to two-step total syntheses of papaveraldine and pulcheotine A. Additionally, the total synthesis of liriodenine is achieved in six steps from homopiperonyl alcohol and 2-bromophenylacetonitrile by applying this catalytic tandem oxidation. Moreover, the direct conversion of xylopinine to 8-oxypseudopalmatine in a 76% yield demonstrates the versatility of this catalytic reaction.
- Nishimoto, Saeko,Nakahashi, Hiromichi,Toyota, Masahiro
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- One-Pot Synthesis of Papaverine Hydrochloride and Identification of Impurities
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Abstract: A one-pot synthesis of papaverine hydrochloride with 99.6% purity was performed using xylene as solvent for the entire process. The critical parameters of each step, as well as the impurities generated, were identified. The overall yield was improved to 63%. The proposed synthetic procedure is suitable for industrial production.
- Qiu, Zeng-Feng,Wu, Ze-Nong,Yang, Zhe-Zhou,Yu, Wen-Shuai,Zhang, Fu-Li,Zhao, Chun-Jie
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p. 1295 - 1299
(2020/09/16)
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- Electrochemical benzylic oxidation of C-H bonds
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Oxidized products have become increasingly valuable as building blocks for a wide variety of different processes and fine chemistry, especially in the benzylic position. We report herein a sustainable protocol for this transformation through C-H functionalization and is performed using electrochemistry as the main power source and tert-butyl hydroperoxide as the radical source for the C-H abstraction. The temperature conditions reported here do not increase above 50 °C and use an aqueous-based medium. A broad substrate scope is explored, along with bioactive molecules, to give comparable and increased product yields when compared to prior reported literature without the use of electrochemistry.
- Marko, Jason A.,Durgham, Anthony,Bretz, Stacey Lowery,Liu, Wei
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supporting information
p. 937 - 940
(2019/01/23)
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- Metal- and radical-free aerobic oxidation of heteroaromatic methanes: An efficient synthesis of heteroaromatic aldehydes
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A metal-free and radical-free synthesis of heteroaromatic aldehydes was developed through aerobic oxidation of methyl groups in an I2/DMSO/O2 catalytic system. Under the reaction conditions, various functional groups such as methoxy, aldehyde, ester, nitro, amide, and halo (F, Cl, Br) groups were well tolerated. The bioactive compounds like chlorchinaldin derivative and papaverine were also oxidized to the corresponding aldehydes and ketones. This reaction provided an efficient method for preparing the valuable heteroaromatic aldehydes.
- Ye, Rongzi,Cao, Yuanjie,Xi, Xiaoxiang,Liu, Long,Chen, Tieqiao
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supporting information
p. 4220 - 4224
(2019/05/10)
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- Visible-Light-Mediated Direct Decarboxylative Acylation of Electron-Deficient Heteroarenes Using α-Ketoacids
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Acylation of electron-deficient heteroaromatic compounds has been developed using visible light. α-Ketoacids have been used as an efficient source of acyl radicals under photoredox conditions. The in situ generated acyl radicals from α-ketoacids have been coupled to a wide variety of electron-deficient heteroaromatic compounds in a Minisci type reaction. This method would be attractive to access biologically attractive molecules.
- Manna, Sabyasachi,Prabhu, Kandikere Ramaiah
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- Novel total syntheses of oxoaporphine alkaloids enabled by mild Cu-catalyzed tandem oxidation/aromatization of 1-Bn-DHIQs
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Novel total syntheses of oxoaporphine alkaloids such as liriodenine, dicentrinone, cassameridine, lysicamine, oxoglaucine and O-methylmoschatoline were developed. The key step of these total syntheses is Cu-catalyzed conversion of 1-benzyl-3,4-dihydro-isoquinolines (1-Bn-DHIQs) to 1-benzoyl-isoquinolines (1-Bz-IQs) via tandem oxidation/aromatization. This novel Cu-catalyzed conversion has been studied in detail, and was successfully used for constructing the 1-Bz-IQ core.
- Zheng, Bo,Qu, Hui-Ya,Meng, Tian-Zhuo,Lu, Xia,Zheng, Jie,He, Yun-Gang,Fan, Qi-Qi,Shi, Xiao-Xin
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p. 28997 - 29007
(2018/08/29)
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- Iron Complex Catalyzed Selective C-H Bond Oxidation with Broad Substrate Scope
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The use of a peroxidase-mimicking Fe complex has been reported on the basis of the biuret-modified TAML macrocyclic ligand framework (Fe-bTAML) as a catalyst to perform selective oxidation of unactivated 3° C-H bonds and activated 2° C-H bonds with low catalyst loading (1 mol %) and high product yield (excellent mass balance) under near-neutral conditions and broad substrate scope (18 substrates which includes arenes, heteroaromatics, and polar functional groups). Aliphatic C-H oxidation of 3° and 2° sites of complex substrates was achieved with predictable selectivity using steric, electronic, and stereoelectronic rules that govern site selectivity, which included oxidation of (+)-artemisinin to (+)-10β-hydroxyartemisinin. Mechanistic studies indicate FeV(O) to be the active oxidant during these reactions.
- Jana, Sandipan,Ghosh, Munmun,Ambule, Mayur,Sen Gupta, Sayam
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supporting information
p. 746 - 749
(2017/03/01)
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- Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen
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The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP-MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit.
- Sterckx, Hans,De Houwer, Johan,Mensch, Carl,Herrebout, Wouter,Tehrani, Kourosch Abbaspour,Maes, Bert U.W.
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supporting information
p. 144 - 153
(2016/04/05)
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- Transition metal-free Minisci reaction promoted by NCS, and TBHP: Acylation of heteroarenes
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A method for acylation for heteroarenes under metal-free conditions has been described using NCS as an additive and TBHP as an oxidant. This method has been successfully employed in acylation of a variety of aldehyde with heteroarenes. The application of the method has been illustrated in synthesizing isoquinoline derived natural products. This strategy provides an efficient, mild and inexpensive method for acylation of heteroarenes.
- Siddaraju, Yogesh,Prabhu, Kandikere Ramaiah
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supporting information
p. 959 - 967
(2016/02/03)
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- A divergent approach to benzylisoquinoline-type and oxoaporphine alkaloids via regioselective direct ring metalation of alkoxy isoquinolines
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Methoxy- and benzyloxy-substituted isoquinolines are regioselectively metalated at C-1 with the Knochel-Hauser base, subsequent trapping with aromatic aldehydes gives aryl(isoquinolin-1-yl)carbinols as building blocks for divergent syntheses of different types of benzylisoquinoline alkaloids. Photochemical cyclization of ortho-bromo analogues under reductive conditions gives oxoaporphine alkaloids. Nine benzylisoquinoline alkaloids and two oxoaporphine alkaloids were obtained in two or three steps from appropriate isoquinolines.
- Melzer, Benedikt,Bracher, Franz
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p. 7664 - 7672
(2015/07/15)
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- A cascade coupling strategy for one-pot total synthesis of β-carboline and isoquinoline-containing natural products and derivatives
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Multi-birds with one stone: A cascade coupling strategy was developed for the synthesis of β-carbolines. The method can direct the synthesis of β-carboline and isoquinoline-containing natural products with high yields. Moreover, this protocol can also be further applied towards the total synthesis of natural products fascaplysin and papaverin (see scheme). Copyright
- Zhu, Yan-Ping,Liu, Mei-Cai,Cai, Qun,Jia, Feng-Cheng,Wu, An-Xin
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supporting information
p. 10132 - 10137
(2013/09/02)
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- Synthesis of isoquinoline alkaloids via oxidative amidation-bischler- napieralski reaction
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A straightforward synthesis of -keto amides by coupling primary amines with aryl dibromoethanones under oxidative amidation conditions has been developed. The -keto amides were then subjected to heterocyclodehydration reaction under Bischler-Napieralski conditions followed by aromatization with DBU provided 1-benzoyl isoquinolines in a two-stage process. Utilizing this methodology, isoquinoline alkaloids such as thalmicrinone, papavaraldine, and pulcheotine A were synthesized in excellent yields. Georg Thieme Verlag Stuttgart · New York.
- Shankar,More, Satish S.,Madhubabu,Vembu,Syam Kumar
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supporting information; experimental part
p. 1013 - 1020
(2012/06/01)
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- Oxidation of 1-benzyldihydroisoquinolines or 1- benzyltetrahydroisoquinolines with dioxygen to 1-benzoylisoquinolines
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An environmental-benign methodology to synthesize 1-benzoylisoquinolines from 1-benzyl-3, 4-dihydroisoquinolines or 1-benzyl-1,2,3,4- tetrahydroisoquinolines using dioxygen as an oxidant was developed. This methodology in combination with Bischler-Napieralski reaction leads to a facile synthesis of 1-benzoylisoquinolines from phenylacetic acids and phenylethanamines.
- Gan, Haifeng,Lu, Yunyu,Huang, Yue,Ni, Lijun,Xu, Jinyi,Yao, Hequan,Wu, Xiaoming
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experimental part
p. 1320 - 1324
(2011/04/15)
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- Strategies and synthetic methods directed toward the preparation of libraries of substituted isoquinolines
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Strategies for the production of substituted isoquinoline libraries were developed and explored. Routes involving microwave-assisted variants of the Bischler-Napieralski or Pictet-Spengler reaction allowed for cyclization of substituted β-arylethylamine derivatives. The dihydroisoquinolines and tetrahydroisoquinolines thus generated could then be oxidized to their corresponding isoquinoline analogues. An alternate strategy, however, involving the preparation and activation of isoquinolin-1(2H)-ones is demonstrated to be a more practical, rapid, and efficient route to C1- and C4-substituted isoquinoline libraries.
- Awuah, Emelia,Capretta, Alfredo
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supporting information; scheme or table
p. 5627 - 5634
(2010/11/03)
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- Photostabilization of papaverine hydrochloride solutions
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The stability of aqueous and non-aqueous papaverine hydrochloride solutions exposed to the UV radiation is poor. In order to enhance its photo-stability suitable light absorbers may be used. There were four photo-protectors considered in this work: 4-aminobenzoic acid, sodium benzoate, methyl 4-hydroxybenzoate and propyl 4-hydroxybenzoate, whose UV absorption spectra characteristics match to some extent with the UV spectrum of papaverine. Approximately 20 mg/mL papaverine chloroform solutions with the above non-toxic additives in the concentrations 0.01; 0.05; 0.10% were exposed to the UV light of 254 nm. High performance capillary electrophoresis was used to determine the papaverine hydrochloride concentration loss as a function of time exposition to the light. It was found that papaverine hydrochloride photolysis proceeds according to the first-order kinetics. Methyl 4-hydroxybenzoate was found to be the best UV radiation-protective agent, and at the concentration 0.10%, the reaction rate constant decreases from 0.143 h-1 to 0.028 h -1. Both 4-hydroxybenzoate esters develop a more efficient UV radiation-protective activity than sodium benzoate, because the latter additive molar extinction coefficient is less significant. However, in spite of a high value of 4-aminobenzoic acid molar absorptivity coefficient, it is an unsuitable photo-protector for papaverine hydrochloride solutions, because its UV absorption spectrum does not match with that of papaverine.
- Piotrowska, Karolina,Hermann, Tadeusz W.,Pawelska, Alicja
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scheme or table
p. 321 - 326
(2011/08/07)
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- Discovery of a series of nonpeptide small molecules that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins
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Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (>100 nM) this large pool of IGF is biologically inactive because of its association with six distinct binding proteins which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants which bind to IGFBPs but not the IGF-I receptor have been shown to be potent IGF/IGFBP inhibitors small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by 1 and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.
- Chen,Zhu,Liu,Lu,Xie,Ling
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p. 4001 - 4010
(2007/10/03)
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- SYNTHESIS OF 2,3,8,9-TETRAMETHOXY-11-PHENYL-5,6-DIHYDRODIBENZINDOLIZINE
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2,3,8,9-Tetramethoxy-11-phenyldibenzindolizine was obtained in high yield from (6,7-dimethoxyisoquinolin-1-yl)-(3,4-dimethylphenyl)phenylcarbinol by cyclization in the presence of formic acid.The behavior of (6,7-dimethoxyisoquinolin-1-yl)-(3,4-dimethoxyphenyl)methylcarbinol and (6,7-dimethoxyisoquinolin-1-yl-(3,4-dimethoxyphenyl)carbinol was studied under these same conditions. 2,3,7,8-Tetramethoxy-11-phenyl-5,6-dihydrodibenzindolizine was obtained by hydrogenation on rhenium heptasulfide.
- Alarcon, Jorge A. R.,Soldatenkov, A. T.,Soldatova, S. A.,Samalloa, Alicia U.,Obando, Juan U.,Prostakov, N. S.
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p. 1054 - 1058
(2007/10/02)
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- Selective inhibition of calcium entry induced by benzylisoquinolines in rat smooth muscle
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The mechanism of relaxant activity of six benzylisoquinolines was examined in order to determine the minimal structural requirements that enable these compounds to have either a non-specific action like papaverine or an inhibitory activity on calcium entry via potential-operated channels. All the alkaloids tested totally or partially relaxed KCl-depolarized rat uterus and inhibited oxytocin-induced rhythmic contractions. Only glaucine and laudanosine inhibited K+-induced uterine contractions more than oxytocin-induced uterine contractions. In Ca+-free medium, sustained contractions induced by oxytocin or vanadate were relaxed by the alkaloids tested except for glaucine and laudanosine indicating no inhibitory effect on intracellular calcium release. Those alkaloids containing an unsaturated heterocyclic ring (papaverine, papaverinol, papaveraldine, N-methylpapaverine and dehydropapaverine) exhibited a more specific activity than those with a tetrahydroisoquinoline ring.
- Anselmi,Fayos,Blasco,Candenas,Cortes,D'Ocon
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p. 337 - 343
(2007/10/02)
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- Dispironaphthalenones and Spironaphthalenones as Novel Dehydrogenation Reagents
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Dehydrogenation of a number of dihydroaromatic substrates has been carried out using either dispironaphthalenone 1 or spironaphthalenones 2 and 3 as dehydrogenating agents.The reaction is over in refluxing mesitylene in 1-2 hr and the yields of the aromatised products are fairly good (65-70percent).
- Kasturi, Tirumalai R.,Sattigeri, Jitendra A.
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p. 6439 - 6444
(2007/10/02)
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- THE CHEMISTRY OF VICINAL TRICARBONYL COMPOUNDS. APPLICATIONS IN THE SYNTHESIS OF ISOQUINOLINE ALKALOIDS
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The central carbonyl of a vicinal tricarbonyl system is used as a dielectrophile with substituted phenethylamines in short, efficient syntheses of the isoquinoline alkaloids, papaveraldine, hydrastine and cordrastine.
- Wasserman, Harry H.,Amici, Robert,Frechette, Roger,Duzer, John H. van
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p. 869 - 872
(2007/10/02)
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- Oxydation vanadique de la papaverine en milieu sulfurique 2,5 M et 5 M
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Vanadic oxidation of papaverine 1 in 5 M sulfuric acid media shows a full oxidation into carbon dioxide and water.However, according to the experimental conditions, and in 2.5 M and 5 M sulfuric acid media, intermediates and products have been identified: papaveraldine 2, hemipinimide 4, meta-hemipinic acid 3, 6,7-dimethoxy isoquinoline 5, 1-formyl 6,7-dimethoxy isoquinoline 6, 1-acetyl 6,7-dimethoxy isoquinoline 7, 4-hydroxy 6-demethyl papaveraldine 8, 4-hydroxy 4'demethyl papaveraldine 9, 3-hydroxy 6-demethyl papaveraldine 10 and 3-hydroxy 4'-demethyl papaveraldine 11.
- Postaire, E.,Martinez, D.,Viel, C.,Chastagnier, M.,Hamon, M.
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p. 982 - 988
(2007/10/02)
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- Lead Tetraacetate Mediated Oxidation of the Enamides Derived from 1-Benzyl-3,4-dihydroisoquinolines
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The products obtained from the lead tetraacetate (LTA) oxidation of N-acylbenzylidene isoquinoline enamides are a function of the type of carbonyl function in the enamide, the solvent,and the type of substitution on the benzylidene aromatic ring.The benzoyl enamides yield Z-β-acethoxy-substituted enamides.The ethoxycarbonyl enamides, containing electron-releasing substituents on the benzylidene ring, efficiently form oxazolones when oxidized with LTA in acetic acid.In the absence of electron-releasing substituents, ring opening occurs to form benzoin esters.When the same oxidation is conducted in benzene, the enamide double bond is converted into its diacetoxy derivative, which can undergo a variety of reactions.LTA oxidation of acetyl enamides results in cleavage of the acetyl group with ultimate formation of 1-benzoyl-3,4-dihydroisoquinolines and isoquinolines.Oxidation of the formyl enamide with LTA results in cleavage of the formyl group with formation of a variety of products.Most of these have an acetyl group in place of the original formyl and are the result of either cleavage of the benzylidene ring at the double bond, oxidation, and subsequent ring opening to a benzil or various other oxidative and rearrangement processes.
- Lenz, George R.,Costanza, Carl
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p. 1176 - 1183
(2007/10/02)
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- ALKYLATION OF 1-(3,4-DIMETHOXYBENZYL)-6,7-DIMETHOXYISOQUINOLINE (PAPAVERINE)
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Alkylation of papaverine carboanion with various alkyl halides is described.Intramolecular ring formation is observed with 1-iodo-3-chloropropane as electrophile. 1--6,7-dimethoxyisoquinoline is studied.
- Buzas, Andre,Merour, Jean-Yves,Lavielle, Gilbert
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p. 2561 - 2570
(2007/10/02)
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- Hofmann Degradation of β-Hydroxy Ammonium Salts. α- and β-Hydroxylaudanosine, 7-Hydroxyglaucine, and 13-Hydroxyxylopinine
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The four related β-hydroxy ammonium methiodide salts of α-hydroxylaudanosine (2a), β-hydroxylaudanosine (2b), 7-hydroxyglaucine (5a), and 13-hydroxyxylopinine (8a) have been subjected to Hofmann degradation.Although precedent dictates that such materials should form either epoxides or ketones, these are not found.Only products of (a) fragmentation and elimination (from 2a and 2b), (b) dehydration and elimination (from 5a), and (c) elimination and oxidation (from 8a) are obtained.The results are accounted for by consideration of the molecular geometries of theβ-hydroxy ammonium salts as experimentally determined from single-crystal X-ray studies and the geometric requirements for epoxide and ketone formation.
- Wert, Kathleen L.,Chackalamannil, Samuel,Miller, Eric,Dalton, David R.,Zacharias, David E.,Glusker, Jenny P.
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p. 5141 - 5150
(2007/10/02)
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- FREMY'S SALT OXIDATION OF SOME ISOQUINOLINE ALKALOIDS. BIOGENETIC CONSIDERATIONS
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Fremy's salt oxidation of benzylisoquinoline and aporphine alkaloids to isoquinolones and oxoaporphines is described.Aminium radicals are suggested to account for the observed results.Their possible involvement in alkaloid biosynthesis is considered.
- Castedo, Luis,Puga, Alberto,Saa, Jose M.,Suau, Rafael
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p. 2233 - 2236
(2007/10/02)
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