- Synthesis of cyclopropanated [2.2.1] heterobicycloalkenes: An improved procedure
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A safer and improved method to our previous report on palladium-catalyzed cyclopropanation of heterobicyclic alkenes has been developed. By using tetrahydrofuran as the solvent and a more dilute aqueous NaOH solution for the generation of diazomethane fro
- Carlson, Emily,Duret, Guillaume,Blanchard, Nicolas,Tam, William
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- Scalable On-Demand Production of Purified Diazomethane Suitable for Sensitive Catalytic Reactions
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We have developed a convenient development-scale reactor (0.44 mol/h) to prepare diazomethane from N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in ~80% yield. Diazomethane (CH2N2) made with this reactor is extracted into nitrogen gas from the liquid reaction mixture, effectively removing it from reagents and byproducts that may interfere in subsequent reactions. Vertically oriented tubular reactors were used to produce and consume diazomethane in situ. Key features of this reactor include high productivity and correspondingly low reactor volume (reactor volume/liquid flow rate = 6.5 min) and a commercially available gas/liquid separator equipped with a selectively permeating hydrophilic membrane. The design of the reactor keeps the inventory below 53 mg of CH2N2 during normal operation. The reactor was demonstrated by generating CH2N2 that was used in a connected continuous reactor. We evaluated esterification reactions and a continuous Pd-catalyzed cyclopropanation reaction with the reactor and achieved high conversion with 1.5 and 4.1 equiv of MNTS precursor, respectively.
- Sheeran, Jillian W.,Campbell, Kiersten,Breen, Christopher P.,Hummel, Gerald,Huang, Changfeng,Datta, Anamika,Boyer, Serge H.,Hecker, Scott J.,Bio, Matthew M.,Fang, Yuan-Qing,Ford, David D.,Russell, M. Grace
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- BACKBONE REARRANGEMENTS OF METHYL (-)-KAUR-9(11)-EN-19-OATE AND ITS EPOXIDE: STRUCTURES OF TWO DITERPENES OF A NEW SKELETAL TYPE
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Cleavage of the epoxide (2) of methyl (-)-kaur-9(11)-en-19-oate (1b) with boron trifluoride-ether in benzene and in acetic anhydride yielded (3a) and (3b), respectively.On epoxidation with m-chloroperbenzoic acid in the presence of N-nitrosomethyl urea, (1b) suffered a backbone rearrangement to form (6).
- Nakano, Tatsuhiko,Spinelli, A. C.,Martin, A.,Usubillaga, A.,McPhail, Andrew P.,Onan, Kay D.
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- How nucleophilic are diazo compounds?
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The kinetics of the reactions of benzhydryl cations with eight diazo compounds 1a-g were investigated photometrically in dichloromethane. The nucleophilicity parameters N and slope parameters s of these diazo compounds were derived from the equation log k
- Bug, Thorsten,Hartnagel, Manfred,Schlierf, Clemens,Mayr, Herbert
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- A carbonyl ylide cycloaddition approach to platensimycin
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(Chemical Presented) Short and to the point: A formal synthesis of platensimycin has been accomplished by employing a carbonyl ylide [3+2] cycloaddition reaction (see scheme). This short and facile enantioselective synthesis of the pivotal tetracyclic precursor requires 11 steps and proceeds in 20% overall yield from isopropyl cyanoacetate.
- Kim, Chan Hyuk,Jang, Ki Po,Choi, Soo Young,Chung, Young Keun,Lee, Eun
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- The synthesis of O-substituted 3-oximes of 6α -methyl-16α, 17α-cyclohexanopregn-4-ene-3,20-diones tritium-labeled in the 1,2-position
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1,2-Tritium-labeled 3-(O-carboxypropyl)- and 3-(O-carbomethoxypropyl)- oximes of 6α-methyl-16α,17α-cyclohexanopregn-4-ene-3,20-diones were obtained by the homogeneous catalytic hydrogenation of 1,2-dehydroprecursors with gaseous tritium and the subsequent separation of the resulting mixtures by HPLC. The specific radioactivities of 50-55 Ci/mmol were prepared using tris-(triphenylphosphine)-rhodium chloride.
- Shevchenko,Nagaev,Levina,Kulikova,Myasoedov,Kamernitzky
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- Concise synthesis of alkaloid (-)-205B
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Described herein is a short total synthesis of alkaloid (-)-205B (1) by means of an anti-selective SN2 alkylation of an attractively functionalized cyclopropanol and diastereoselective cyclization of the resulting aminoallene adduct for bicyclic ring formation. The synthesis features a general route to cis- or trans-2,6-disubstituted piperidines by lithium aluminum hydride reduction of the imine intermediate by an appropriate choice of solvent and cis- or trans-2,5-disubstituted pyrrolidines by an exceptional level of chirality transfer from a pendant allene. Particularly noteworthy are the brevity and convergence made possible by a segment-coupling strategy.
- Rao, Nagavaram Narsimha,Cha, Jin Kun
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- Preparation of a bicyclic analogue of qinghao (artemisinic) acid via a Lewis acid catalyzed ion Diels-Alder reaction involving a hydroxy diene and cyclic enone and facile conversion into (±)-6,9-desdimethylqinghaosu
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Treatment of 6-methylcyclohex-2-enone (8) and hexa-3,5-dien-1-ol (14) either in dichloromethane at -20 to 0°C with aluminum chloride (1 equiv) or in acetonitrile at -20°C with Cu(II) trifluoromethanesulfonate (1 equiv) rapidly provides in a highly stereoselective reaction the hemiacetal Diels-Alder adduct 15, which with a trans ring junction and anti methyl group is considered to arise via an ionic Gassman-type Diels-Alder reaction involving prior formation of a hemiacetal between the alcohol and enone followed by generation of an allylic cation from the hemiacetal mediated by the Lewis acid. The adduct 15 is then converted in straightforward fashion into the methyl ester of the desdimethyl analogue of qinghao (artemisinic) acid, which upon sequential photosensitized oxygenation and then Fe(phen)3(PF6)3/copper(II) triflate catalyzed cleavage-oxygenation provides (±)-6,9-desdimethylqinghaosu.
- Haynes,King,Vonwiller
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- An enantiospecific synthesis of a komarovispirane
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The enantiospecific total synthesis of a komarovispirane, containing the complete carbon framework, trans-bicyclo[4.3.0]nonanespiro[8.1′]cyclohexane, of the spiroditerpene komarovispirone, starting from the readily available campholenaldehyde is described
- Srikrishna, Adusumilli,Beeraiah
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- Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists
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On the basis of the structural similarity of our previous 5-HT2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofu
- Cheng, Jianjun,McCorvy, John D.,Giguere, Patrick M.,Zhu, Hu,Kenakin, Terry,Roth, Bryan L.,Kozikowski, Alan P.
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- Isolation and structural identification of a direct-acting mutagen derived from N-nitroso-N-methylpentylamine and Fenton's reagent with copper ion
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N-Nitrosodialkylamines show their mutagenicity by forming α-hydroxynitrosamines in the presence of rat S9 mix in the Ames assay. The hydroxyl radical derived from Fe2+-H2O2 (Fenton's reagent) with Cu2+ activates N-nitrosamines, with an alkyl chain longer than a propyl constituent, to a direct-acting mutagen. The reactivity of Fe2+-Cu2+-H2O2 on nitrosamines in relation to their metabolic activation is not fully characterized. Here, we report the identification of the direct-acting mutagen derived from N-nitroso-N-methylpentylamine (NMPe) in the presence of Fe 2+, Cu2+, H2O2 and nitric oxide (NO), which is a product of nitrosamine metabolism. A dichloromethane extract of the NMPe reaction mixtures was fractionated by silica gel column chromatography several times and by a preparative high performance liquid chromatography (HPLC); we obtained white crystals as a product. The direct-acting mutagen that was isolated was provisionally identified as 5-ethyl-5-nitro-1-pyrazoline 1-oxide by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and X-ray crystallography. To confirm the structure of the mutagen, the authentic compound was synthesized from 2-nitrobutene and diazomethane, followed by N-oxidation with m-chloroperoxybenzoic acid. The 1H NMR spectral data from the direct-acting mutagen that was synthesized was identical to the data from the isolated mutagen. Furthermore, the authentic 5-ethyl-5-nitro-1-pyrazoline 1-oxide was mutagenic in Salmonella typhimurium TA1535. The results showed that 5-ethyl-5-nitro-1-pyrazoline 1-oxide was a direct-acting mutagen derived from the reaction of NMPe and Fe2+-Cu2+-H2O 2-NO.
- Miura, Motofumi,Inami, Keiko,Yoshida, Masafumi,Yamaguchi, Kentaro,Mashino, Tadahiko,Mochizuki, Masataka
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- Secondary metabolites from anti-insect extracts of endophytic fungi isolated from Picea rubens
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The extracts of a selection of 150 foliar fungal endophytes isolated from Picea rubens (red spruce) needles were screened by LC-MS and assayed for toxicity. Three of these strains that were toxic to the forest pest Choristoneura fumiferana (eastern spruce budworm) in dietary bioassays were selected for further study. Their culture extracts were analyzed by LC-NMR spectroscopy, and the major metabolites were isolated by LC-MS-SPE or PTLC/column chromatography and characterized. The structures were elucidated by spectroscopic analyses including 2D NMR, HRMS and by comparison to literature data. Compounds 1 and 5-7 are hitherto unknown whereas compounds 2 and 3 are natural products described for the first time. Compound 4 is reported for the first time as a fungal metabolite and 8-9 were identified as known fungal metabolites in genera.
- Sumarah, Mark W.,Puniani, Eva,S?rensen, Dan,Blackwell, Barbara A.,Miller, J. David
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- Carbenoid insertion into the peroxide bond vs the olefin bond of cyclic peroxides
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(Chemical Equation Presented) Herein we report examples of the insertion of a carbenoid into a peroxide linkage. This study reveals that intramolecular insertion of carbenes into the peroxide linkage of 3,6-dihydro-1,2-dioxines is preferred over olefin insertion. The initial scope of the reaction and mechanistic considerations, have been probed. This methodology also generates unusual bicyclic hemiacetals (2) and tricyclic peroxides (3).
- Zvarec, Ondrej,Avery, Thomas D.,Taylor, Dennis K.
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- Mechanism of decomposition of (E)-methanediazoate in aqueous solutions
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Rate constants for the decomposition of (E)-methanediazoate (1) at 25°C, ionic strength 1 M (NaClO4), are independent of the concentration of nucleophile in up to 0.25 M propylamine base, 0.5 M methoxyamine base, 0.20 M thiosulfate dianion, and 0.50 M azide ion. When the CH3 group of 1 is transferred to benzoate ions, benzyl alcohol, and water upon decomposition in near neutral D2O solutions, the isotopic integrity of the methyl group is maintained to the extent of 70-90%. The rate constant for the decomposition of protonated 1 in ethanol is 680 times slower than that in aqueous 4% ethanol under identical buffering and ionic strength conditions. Trapping of the methyl group derived from 1 by two pairs of nucleophiles gives the same ratios of methylated products as those determined from the decomposition of diazomethane. The solvent deuterium isotope effect for the decomposition of the protonated form of 1 is kH2o/kH2O = 1.49 ± 0.09, and the activation parameters for its decomposition are ΔH? = 69.6 ± 1.5 kJ/mol and ΔS? = -4.5 ± 9.5 J/deg mol. It is concluded that 1 decomposes via equilibrium protonation on oxygen with subsequent rate-limiting cleavage of the O-N bond of the diazoic acid to yield the methanediazonium ion. This conclusion and measurements of the rate constants for decomposition of diazomethane under comparable conditions (25°C, aqueous 5% acetonitrile, ionic strength 0.20 M) permit the first semiquantitative description of the decomposition of a simple alkanediazoate and associated intermediates in wholly or predominately aqueous media.
- Hovinen, Jari,Finneman, Jari I.,Satapathy, Surya N.,Ho, Jian,Fishbein, James C.
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- Vibrational Energy Distributions of Singlet Methylene from Photolyses Ketene, Ketene-d2, Diazomethane, and Diazomethane-d2 at Several Wavelengths. A Chemically Activated Methylcyclobutene Study
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The energy distributions of singlet methylene upon reaction with cyclobutane have been determined for methylene from photolysis of ketene and ketene-d2 at 214 nm, diazomethane at 436, 366, 337, 229 nm, and diazomethane-d2 at 366 nm.Earlier results for diazomethane photolyses at 436 and 366 nm are extended and reanalyzed in terms of a more recent stepsize determination for collosional deactivation of chemically activated methylcyclobutane.The widths of the singlet methylene energy distributions were found to increase with increasing photon energy and with deuterium substitution.An extensive analysis in terms of a statistical energy partitioning model for photodissociation of ketene and diazomethane is given and discussed.
- Mahone, W. C.,Kolln, W.,Simons, J. W.
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- X-ray crystal structure of grandiflorenic acid [(-)-kaura-9(11)-16-dien-19- oic acid] methyl ester, a compound formerly considered as an oily derivative
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Grandiflorenic acid [(-)-kaura-9(11)-16-dien-19-oic acid] methyl ester (2), C21H30O2, was synthesized from grandiflorenic acid, isolated from the plant Montanoa tomentosa. Compound (2) was formerly described as an oily derivative. X-ray diffraction analysis of (2) demonstrated that it consists of four rings, three six-membered rings (I, II and III) and one five-membered ring (IV). I, II and III rings occur in chair, twist, and envelope conformations, respectively. Ring IV occurs in a conformation between envelope and half-chair. The crystal of grandiflorenic acid methyl ester is in monoclinic crystal system with space group P21, lattice constants: a = 7.2170(10), b = 11.4170(10), c = 11.2850(10) A, β = 98.700(10)°, V = 919.1(2) A3 and Z = 2.
- Cruz-Mondragon, Perla,Concepcion Lozada,Ortiz, Benjamin,Enriquez, Raul G.,Soriano-Garcia, Manuel
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- Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (anacardiaceae): Structure/activity relationships
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Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 μg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 μg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.
- Morais, Thiago R.,Da Costa-Silva, Thais A.,Tempone, Andre G.,Borborema, Samanta Etel T.,Scotti, Marcus T.,De Sousa, Raquel Maria F.,Araujo, Ana Carolina C.,De Oliveira, Alberto,De Morais, Sergio Antonio L.,Sartorelli, Patricia,Lago, Joao Henrique G.
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- Enantiospecific synthesis of angular triquinanes
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The enantiospecific synthesis of angular triquinanes has been developed starting from the readily available (S)-campholenaldehyde. Two alternate strategies have been used, one employing a Johnson's orthoester Claisen rearrangement followed by an intramolecular cyclopropanation and regioselective cyclopropane ring cleavage, and a second one based on a RCM reaction.
- Srikrishna, Adusumilli,Gowri, Vijayendran
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- Synthesis of carbazole analogs via Grob fragmentation of norbornyl α-diketones
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A regioselective synthesis of carbazole analogs belonging to both the categories of natural origin, viz., microorganisms and higher plant source is reported. The synthesis of carbazole derivatives possessing a methylester group at C-1 position has been ac
- Sravanthi, Kadavergu,Agrawal, Sumit Kumar,Rao, Chintada Nageswara,Khan, Faiz Ahmed
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- Pyrenes and pyrendiones from Uvaria lucida
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A chemical investigation of the chloroform extract of the roots of Uvaria ludida Benth. (Annonaceae), an important African traditional medicine, led to the isolation of six new compounds; three pyrenes, 2-hydroxy-1,8- dimethoxypyrene (1), 8-methoxy-1,2-methylenedioxypyrene (2), and 7-hydroxy-8-methoxy-1,2-methylenedioxypyrene (3), two pyrenediones, 2-hydroxy-1,8-pyrenedione (4) and 2-methoxy-1,8-pyrenedione (5), and a sesquiterpene, (-)-10-oxo-isodauc-3-en-15-oic acid (6), together with eight known compounds (7-14). The structural elucidation by spectroscopic studies of the compounds isolated is described. While pyrenes did not exhibit strong cytotoxicity against human promyelocytic leukemia HL-60 cells, pyrenediones showed strong cytotoxicity. The IC50 of 4 was 70 ng mL-1, which was close to that of etoposide (IC50 = 60 ng mL-1). The Japanese Society of Pharmacognosy and Springer 2011.
- Moriyasu, Masataka,Takeuchi, Sousuke,Ichimaru, Momoyo,Nakatani, Noriyshi,Nishiyama, Yumi,Kato, Atsushi,Mathenge, Simon G.,Juma, Francis D.,ChaloMutiso, Patrick B.
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- Design and synthesis of novel xyloketal derivatives and their vasorelaxing activities in rat thoracic aorta and angiogenic activities in zebrafish angiogenesis screen
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A novel series of xyloketal derivatives (1-21) were designed and prepared. The majority of the compounds demonstrated vasorelaxation action on 60 mM KCl-induced contractions rat isolated aortic rings in a concentration-dependent manner, and the action is mediated by both endothelium-independent and endothelium-dependent mechanisms. Compounds 9, 12, 13, 14, 15, and 19 showed higher vasorelaxation activities comparing with the lead compound 3. In addition, these derivatives had potential protective action against oxLDL-induced endothelial oxidative injury and enhanced NO production in HUVECs without toxic effects. The NO release was completely inhibited by eNOS inhibitor L-NAME. Furthermore, 3 significantly promoted the angiogenesis in zebrafish in a concentration-dependent manner at 0.1, 1, and 10 μM. Compounds 9, 12, 14, 16, 20, and 21 exhibited stronger angiogenic activities than 3. Therefore, xyloketal derivatives are unique compounds with multiple pharmacological properties and may have potential implications in the treatment of cardiovascular diseases.
- Xu, Zhongliang,Li, Yiying,Xiang, Qi,Pei, Zhong,Liu, Xilin,Lu, Bingtai,Chen, Ling,Wang, Guanlei,Pang, Jiyan,Lin, Yongcheng
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- Unsymmetrically, Chemically Activated 1,2-Dicyclopropylacetylene: An Example of Restricted Energy Flow?
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The Doering-Gilbert-Leermakers strategy for revealing chemical reaction possibly more rapid than internal flow of energy is applied to 1,2-dicyclopropylacetylene by examining addition of dideuteriomethylene to 1-cyclopropyl-2-vinylacetylene and of methylene to 1-(2,2-dideuteriocyclopropyl)-2-vinylacetylene in the gas phase.This reduction to practice of the general strategy has three advantages: one of the three isomers of allylcyclopropylacetylene, itself the key product of chemically activated rearrangement, bears internal witness to the achievement of structural symmetry prior to its generation; the long, linear acetylenic linkage precludes internal energy flow by a mechanism of intramolecular collision; and the activation energy of the cyclopropane-propene rearrangement is lowered significantly.Analysis of the experimental results reveals a small amount of rearrangement at high pressures occurring prior to complete symmetrization of structure and/or energy.If this observation can be ascribed to incomplete symmetrization of energy, the basic premise of the Rice-Ramsperger-Kassel-Marcus theory-that internal energy flow be so much faster than chemical reaction that a structureless statistical treatment is justified-may require reconsideration.
- Doering, W. von E.,Ehlhardt, William J.
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- Syntheses of spiroindole melatonin analogues via 2-(indolin-3-ylidene)acetonitrile cycloadditions
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2-(2-Oxo-1,2-dihydro-3H-indol-3-ylidene)acetonitriles were subjected to cycloaddition reactions at the double bond affording spiroindole melatonin analogues.
- Lozinskaya, Natalia A.,Volkova, Maria S.,Seliverstov, Michael Yu.,Temnov, Victor V.,Sosonyuk, Sergey E.,Proskurnina, Marina V.,Zefirov, Nikolai S.
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- Synthesis of Cyclopropanated 7-Azabenzonorbornadienes
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7-Azabenzonorbornadienes bearing various aryl or N-substituents were treated with diazomethane in the presence of palladium to afford desirable yields of cyclopropanated products (75-98%). The current approach suggests an efficient synthesis for CH2-cyclopropanated 7-azabenzonorbornadienes which lends promise to the development of new ring-opening preparations of biologically useful organic frameworks.
- Carlson, Emily,Tam, William
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- Stereospecific mono- and difluorination of the C7-bridge of norbornenes
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Fluorinated norbornenes are very desirable monomers in the semiconductor and high-temperature polyimide industries. We describe herein a synthetic strategy for the stereospecific mono- or difluorination of the C 7-carbon in norbornene systems beginning with 7-ketonadic anhydride 1. In particular, anti-7-fluoro methyl diester 4 and its 7,7-difluoronadic analog 7 can be prepared from 1 in 3 or 4 steps: saponification, reduction (for 4), esterification, fluorination with DAST. In addition, anti-7-fluoro-syn-7- fluoromethylnadic diester 16 is obtained from epoxide 14, and dimethyl 7,7-difluorobicyclo[2.2.2]oct-5-ene-2,3-dicarboxylate (17) from ketone 15. Anchimeric assistance of the norbornene double bond guides the introduction of attacking fluoride anions stereospecifically anti to the olefinic linkage.
- Rajsfus, David E.,Alter-Zilberfarb, Sari,Sharon, Pessia,Meador, Mary Ann B.,Frimer, Aryeh A.
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- The Rates of Diazomethane Formation from Methylnitrosoamides. The Stability of Diazomethane Solutions towards Aqueous Alkalis
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The rate of hydrolysis of N-methyl-N-nitrosoamides by aqueous alkalis varies greatly.Methylnitrosourea (1) is hydrolyzed rapidly by aqueous KOH-solutions at low temperatures to give a high yield of diazomethane.Under similar conditions, N,N'-dimethyl-dinitroso-oxamide (3) is hydrolyzed more slowly, but also gives a good yield of diazomethane.N,N'-Dimethyl-N,N'-dinitrosoterephthalamide (4), and (N-methyl-N-nitroso)-4-amino-4-methyl-2-pentanone (5) are less easily hydrolyzed by aqueous KOH-solutions.N-Methyl-N-nitroso-p-toluenesulfonamide (2) was the least reactive out of those tested.The hydrolysis of diazomethane in toluene with aqueous bases follows first order kinetics.The hydrolysis rate is greatly influenced by the concentration and strength of the base and temperature.
- Pearce, Michael
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- Perfluoro-tert-butyl-homoserine as a sensitive 19F NMR reporter for peptide-membrane interactions in solution
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Fluorine (19F) NMR is a valuable tool for studying dynamic biological processes. However, increasing the sensitivity of fluorinated reporter molecules is a key to reducing acquisition times and accessing transient biological interactions. Here,
- Buer, Benjamin C.,Levin, Benjamin J.,Marsh, E. Neil G.
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- Stereoselective synthesis of γ-lactone fused cyclopentanoids
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The stereoselective synthesis of γ-lactone fused cyclopentanoids applying chemoenzymatic methods is described. rac-2-Hydroxymethyl-1,4,5,6- tetrachloro-7,7-dimethoxybicyclo[2.2.1]hept-5-ene and rac-2-hydroxymethyl-1,4,5, 6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene were successfully resolved by Candida rugosa lipase (CRL), to afford enantiomerically enriched products with an ee of 94 and 97%, respectively. The enantiomerically enriched acetates were then subjected to ruthenium and/or cerium catalyzed oxidation to afford α-diketones and subsequent alkaline H2O2 mediated oxidative cleavage reaction of α-diketones, followed by CH 2N2 esterification, gave enantiomerically enriched γ-lactone fused cyclopentanoids with known absolute configurations.
- Guemues, Ayseguel,Tanyeli, Cihangir
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- Synthesis of halo-substituted framework derivatives of quinopimaric acid
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6-Chloro-, 6-chloroacetoxy-, and 16-(2-bromoacetyl)framework derivatives were synthesized from a photoadduct of quinopimaric acid.
- Vafina,Uzbekov,Galin,Yunusov
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- An efficient process for synthesis of 2′-O-methyl and 3′-O-methyl guanosine from 2-aminoadenosine using diazomethane and the catalyst stannous chloride
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An improved strategy for the selective synthesis of 2′- O -methyl and 3′- O -methyl guanosine from 2-aminoadenosine is reported by using the catalyst stannous chloride. The regioselectivity of the 2′ and 3′- O -alkylation was achieved by optimizing the addition, timing, and concentration of the catalysts and diazomethane during the methylation reaction. An efficient and selective alkylation at 2′-OH of 2-aminoadenosine was achieved by mixing a stoichiometric amount of stannous chloride at room temperature in DMF. The reaction mixture was stirred at 50°C for 1 min and immediately followed by addition of diazomethane. The resulting 2′- O -methyl 2-aminoadenosine was treated with the enzyme adenosine deaminase, which resulted in an efficient conversion to the desired 2′- O -methylguanosine (98% yield). The product was isolated by crystallization. In contrast, the methylation at 3′-OH of 2-aminoadenosine was achieved by mixing a stoichiometric amount of stannous chloride in DMF and stirring at 50°C for 15 min, followed by addition of diazomethane. The resulting mixture containing 3′- O -methyl-2- aminoadenosine in 90% yield and 2′- O -methyl-2-aminoadenosine in 10% yield was treated with the enzyme adenosine deaminase, which preferentially deaminated only 3′- O -methyl-2-aminoadenosine, resulting in the production of 3′- O -methylguanosine in 88% yield. Due to the extremely low solubility 3′- O -methylguanosine, the compound precipitated and was isolated by centrifugation. This synthetic route obviates the chromatographic purification. Selective monomethylation is achieved by using the unprotected ribonucleoside. As a result, the method described herein represents a significant improvement over the current synthetic approach by providing superior product yield and economy, a much more facile purification of 2′,3′- O -methylated isomers, and eliminating the need for protected ribonucleosides reagents. Copyright Taylor & Francis Group, LLC.
- Kore, Anilkumar,Parmar, Gaurang,Reddy, Srinu
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- Synthetic studies on strictamine: Unexpected oxidation of tertiary amine in Ru-catalyzed ring-closing olefin metathesis
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During synthetic studies toward strictamine, unexpected oxidation of tertiary amine to enamine was observed in ring-closing olefin metathesis (RCM) using Hoveyda-Grubbs 2nd catalyst. Control experiments under deoxygenated conditions indicated Ru-catalyst
- Komatsu, Yoshiyuki,Yoshida, Kei,Ueda, Hirofumi,Tokuyama, Hidetoshi
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- PROTONATION OF DIAZOMETHANE IN SUPERACID MEDIA.
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Protonation on both terminals of diazomethane can be observed only under conditions of kinetic control in extremely acidic solutions, when the acidity is reduced only the thermodynamically more stable C-protonated isomer can be seen. Loss of nitrogen from the methanediazonium ion is nucleophile assisted in the very highly acidic medium of HOSO//2F/SbF//5/SO//2ClF.
- McGarrity,Cox,Phillip
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- AUTOMATED DIAZOMETHANE GENERATOR, REACTOR AND SOLID PHASE QUENCHER
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An automated apparatus (Diazo-M-pen and Diazo-M-cube) for production, utilization and quenching of highly toxic diazomethane comprising of integrated pumps, tubular flow reactor, liquid-liquid micro-separator, solid MOF quencher etc.
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- A simple method of synthesis of 3-carboxy-2,2,5,5-tetraethylpyrrolidine-1-oxyl and preparation of reduction-resistant spin labels and probes of pyrrolidine series
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Stable free radicals are widely used as molecular probes and labels in various biophysical and biomedical research applications of magnetic resonance spectroscopy and imaging. Among these radicals, sterically shielded nitroxides of pyrrolidine series demonstrate the highest stability in biological systems. Here, we suggest new convenient procedure for preparation of 3-carboxy-2,2,5,5-tetraethylpyrrolidine-1-oxyl, a reduction-resistant analog of widely used carboxy-Proxyl, from cheap commercially available reagents with the yield exceeding the most optimistic literature data. Several new spin labels and probes of 2,2,5,5-tetraethylpyrrolidine-1-oxyl series were prepared and reduction of these radicals in ascorbate solutions, mice blood and tissue homogenates was studied.
- Dobrynin, Sergey A.,Usatov, Mikhail S.,Zhurko, Irina F.,Morozov, Denis A.,Polienko, Yuliya F.,Glazachev, Yurii I.,Parkhomenko, Dmitriy A.,Tyumentsev, Mikhail A.,Gatilov, Yuri V.,Chernyak, Elena I.,Bagryanskaya, Elena G.,Kirilyuk, Igor A.
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- Biological evaluation of 3-benzylidenechromanones and their spiropyrazolines-based analogues
-
A series of 3-benzylidenechrmanones 1, 3, 5, 7, 9 and their spiropyrazoline analogues 2, 4, 6, 8, 10 were synthesized. X-ray analysis confirms that compounds 2 and 8 crystallize in a monoclinic system in P21/n space groups with one and three molecules in each asymmetric unit. The crystal lattice of the analyzed compounds is enhanced by hydrogen bonds. The primary aim of the study was to evaluate the anti-proliferative potential of 3-benzylidenechromanones and their spiropyrazoline analogues towards four cancer cell lines. Our results indicate that parent compounds 1 and 9 with a phenyl ring at C2 have lower cytotoxic activity against cancer cell lines than their spiropyrazolines analogues. Analysis of IC50 values showed that the compounds 3 and 7 exhibited higher cytotoxic activity against cancer cells, being more active than the reference compound (4-chromanone or quercetin). The results of this study indicate that the incorporation of a pyrazoline ring into the 3-arylideneflavanone results in an improvement of the compounds’ activity and therefore it may be of use in the search of new anticancer agents. Further analysis allowed us to demonstrate the compounds to have a strong inhibitory effect on the cell cycle. For instance, compounds 2, 10 induced 60% of HL-60 cells to be arrested in G2/M phase. Using a DNA-cleavage protection assay we also demonstrated that tested compounds interact with DNA. All compounds at the concentrations corresponding to cytotoxic properties are not toxic towards red blood cells, and do not contribute to hemolysis of RBCs.
- Adamus-Grabicka, Angelika A.,Budzisz, Elzbieta,Cieslak, Marcin,Hikisz, Pawe?,Królewska-Golinska, Karolina,Kusz, Joachim,Ma?ecka, Magdalena,Markowicz-Piasecka, Magdalena
-
-
- The reagent Et2AlX/CH2N2 in cyclopropanation of sterically hindered olefins, as well as oxygen- and nitrogen-containing unsaturated compounds
-
A transition-metal-free method of cyclopropanation of sterically hindered olefins, substituted allylic alcohols, allylamines, and vinyl silyl ethers was developed using diazomethane in the presence of organic aluminum halides.
- Ramazanov,Yaroslavova,Yaubasarov,Gil’manova,Dzhemilev
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p. 1869 - 1873
(2019/10/22)
-
- Discovery of Vilaprisan (BAY 1002670): A Highly Potent and Selective Progesterone Receptor Modulator Optimized for Gynecologic Therapies
-
Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the treatment of such diseases. Steroidal SPRMs, including mifepristone and ulipristal acetate, have proven effective in clinical trials. However, several steroidal SPRMs containing a dimethylamino substituent have been associated with elevated liver enzymes in patients. An earlier drug discovery program identified lonaprisan as a highly selective SPRM that did not show drug-related change in liver enzyme activity. Building on data obtained from that work, here we describe the research program that culminated in the discovery of a novel steroidal SPRM, vilaprisan, which combines an extremely high potency with very favorable drug metabolism and pharmacokinetic properties. Vilaprisan has entered clinical development and is currently undergoing phase 3 clinical trials.
- M?ller, Carsten,Bone, Wilhelm,Cleve, Arwed,Klar, Ulrich,Rotgeri, Andrea,Rottmann, Antje,Schultze-Mosgau, Marcus-Hillert,Wagenfeld, Andrea,Schwede, Wolfgang
-
supporting information
p. 2271 - 2280
(2018/11/21)
-
- Method for preparing cycloheptanone from cyclohexanone through one step
-
A method for preparing cycloheptanone from cyclohexanone through one step comprises the following steps: using diazomethane as a reagent to prepare a saturated low alcohol solution, adding cyclohexanone and a diluted acid catalyst to a diazomethane alcohol solution, carrying out a slow addition ring expansion reaction at 10-50 DEG C, and carrying out water vapor distillation to prepare crude cycloheptanone; and rectifying the crude cycloheptanone to obtain cycloheptanone. A saturated C4 or less low alcohol solution of diazomethane is prepared through the following steps: reacting hydrochloric acid with a methylamine solution, adding urea, adding a saturated sodium carbonate solution, carrying out a refluxing reaction, adding diluted sulfuric acid, reacting sulfuric acid with a sodium nitrite solution, adding a strong alkali solution to generate a diazomethane gas, introducing the diazomethane gas to a cooled receiving bottle provided with the C4 or less low alcohol. The method has the advantages of short synthetic route, simplicity in operation, environmental protection, high product yield, substantial reduction of the cost, and high facilitation of industrial production.
- -
-
Paragraph 0014; 0017; 0020
(2017/03/08)
-
- Synthesis and antimalarial activity of quinones and structurally-related oxirane derivatives
-
A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) 10 μM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule.
- Carneiro, Paula F.,Pinto, Maria C.R.F.,Marra, Roberta K.F.,Da Silva, Fernando De C.,Resende, Jackson A.L.C.,Rocha E Silva, Luiz F.,Alves, Hilkem G.,Barbosa, Gleyce S.,De Vasconcellos, Marne C.,Lima, Emerson S.,Pohlit, Adrian M.,Ferreira, Vitor F.
-
p. 134 - 140
(2015/12/04)
-
- Highly Stereoselective Synthesis of Fluoroalkene Dipeptides via the Novel Chromium(II)-Mediated Carbon-Fluorine Bond Cleavage/New Carbon-Carbon Bond Formation
-
An efficient chromium(II)-mediated reductive coupling reaction of various CBrF2-containing molecules and aldehydes has been developed. This reaction proceeds presumably via the monofluorinated dichromium(III) intermediate generated by the carbon-fluorine bond activation, and provides a general and straightforward access to synthesize a variety of (E)- or (Z)-β-fluoroallylic alcohols in a highly stereoselective manner. Based on the novel reductive coupling, four types of fluoroalkene dipeptide analogues could be stereoselectively prepared.
- Nihei, Takashi,Nishi, Yuji,Ikeda, Natsumi,Yokotani, Saya,Ishihara, Takashi,Arimitsu, Satoru,Konno, Tsutomu
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p. 865 - 881
(2016/03/12)
-
- Synthesis of acacetin and resveratrol 3,5-di-O-β-glucopyranoside using lipase-catalyzed regioselective deacetylation of polyphenol glycoside peracetates as the key step
-
Acacetin and resveratrol 3,5-di-O-β-glucopyranoside were synthesized from naturally abundant naringin and piceid in 65% and 62% overall yield, respectively. The key steps were the regioselective deacetylation of the peracetates of the glycosylated forms with Candida antarctica lipase B (Novozym 435) and Burkholderia cepacia lipase (Amano PS-IM). Deacetylation occurred exclusively at the least hindered position of the aromatic moieties and all acetyl groups in the sugar side chain remained intact. This excellent selectivity enabled regiospecific transformation of the liberated phenolic hydroxy groups, resulting in efficient synthesis of the target molecules.
- Hanamura, Shun,Hanaya, Kengo,Shoji, Mitsuru,Sugai, Takeshi
-
-
- Inhibition of bacterial biofilms and microbial growth with imidazole derivatives
-
Disclosure is provided for imidazole derivative compounds useful to inhibit the formation of biofilms and/or inhibit microbial growth, compositions including these compounds, devices including these compounds, and methods of using the same.
- -
-
Page/Page column 40; 41
(2016/04/26)
-
- Second generation modifiers of colistin resistance show enhanced activity and lower inherent toxicity
-
We recently reported a 2-aminoimidazole-based antibiotic adjuvant that reverses colistin resistance in two species of Gram-negative bacteria. Mechanistic studies in Acinetobacter baumannii demonstrated that this compound downregulated the PmrAB two-compon
- Brackett, Christopher M.,Furlani, Robert E.,Anderson, Ryan G.,Krishnamurthy, Aparna,Melander, Roberta J.,Moskowitz, Samuel M.,Ernst, Robert K.,Melander, Christian
-
supporting information
p. 3549 - 3553
(2016/07/06)
-
- Automated library synthesis of cyclopropyl boronic esters employing diazomethane in a tube-in-tube flow reactor
-
The efficient synthesis of cyclopropyl boronic esters in library format using a diazomethane flow reactor has been achieved. A pivotal component of the system is a fully automated tube-in-tube reactor allowing for safe handling of hazardous diazomethane on repeated small scale and for the generation of larger quantities of product. The setup enables the repeated execution of Pd-catalyzed cyclopropanation reactions without compromising its operation over time.
- Koolman, Hannes F.,Kantor, Stanislaw,Bogdan, Andrew R.,Wang, Ying,Pan, Jeffrey Y.,Djuric, Stevan W.
-
supporting information
p. 6591 - 6595
(2016/07/16)
-
- METHOD FOR THE PREPARATION OF DIAZOALKANES
-
The present invention relates to a method of forming diazoalkanes. One aspect of the present invention provides a method for the production of a N-alkyl-N-nitroso compound from a starting material, comprising the use of a tribasic acid to acidify an amine. A second aspect of the present invention provides a method for the production of a diazoalkane, comprising reacting a N-alkyl-N-nitroso compound with a base and a phase transfer catalyst, wherein no organic solvent is used.
- -
-
Paragraph 0075-0085
(2015/02/19)
-
- Stereoselective synthesis of cis-2,6-disubstituted morpholines and 1,4-oxathianes by intramolecular reductive etherification of 1,5-diketones
-
A simple and efficient, Lewis acid catalysed reductive etherification strategy for the stereoselective synthesis of cis-2,6- disubstituted morpholines and 1,4-oxathianes starting from readily available 1,5-diketones has been developed. The strategy is used in the total synthesis of morpholine-based natural products (±)-chelonin A and formal total synthesis of (±)-chelonin C.
- Gharpure, Santosh J.,Anuradha, Dandela,Prasad, Jonnalagadda V. K.,Rao, Pidugu Srinivasa
-
supporting information
p. 86 - 90
(2015/01/16)
-
- Cationic mixed micelles as reaction medium for hydrolysis reactions
-
The influence of cationic mixed micelles composed of quartenary ammonium surfactants on hydrolysis reactions has been studied in detail. The basic hydrolysis of N-methyl-N-nitroso-p-toluene sulphonamide has been chosen as the reaction probe, while mixed micelles composed of lauryl trimethyl ammonium chloride and octadecyl trimethyl ammonium chloride with different molar ratios were studied as the reaction medium. The ion-exchange pseudophase model was used to fit the experimental results to obtain the kinetic and thermodynamic parameters of the reaction. The result show that the hydrophobic character of the mixed micelles drives the association of the substrate to them, leading to a local increase of reactant concentrations at the micellar interface and, therefore, to a catalytic effect. By tuning the molar ratio of the mixed micelles it is possible to control substrate binding affinity and thus the catalytic efficiency of the reaction medium.
- Fernández, Isabel,Pérez-Juste, Jorge,Hervés, Pablo
-
p. 1866 - 1874
(2015/10/12)
-
- First enantiospecific syntheses of marine merosesquiterpenes neopetrosiquinones A and B: Evaluation of biological activity
-
The first enantiospecific syntheses of neopetrosiquinones A (6) and B (7), two merosesquiterpenes isolated from the deep-water sponge Neopetrosia cf. proxima, from the labdane diterpene trans-communic acid (10) have been achieved. A key step of the synthetic sequence is the simultaneous aromatization of the C ring and the benzylic oxidation on C-7 of an advanced intermediate, mediated by the oxygen-DDQ system. The in vitro antiproliferative activities of neopetrosiquinone B (7) and of the synthetic intermediates 8 and 9 against human breast (MCF-7), lung (A-549), and colon (T-84) tumor cell lines have been assayed. The most potent was compound 9 (IC50 = 4.1 μM), which was twice as active as natural compound 7 (IC50 = 8.3 μM) against A-549 cells. In addition, the treatment with these compounds resulted in an induction of apoptosis. These findings indicate that the terpene benzoquinones reported here might be potentially useful as anticancer agents.
- Chayboun, Ikram,Boulifa, Ettahir,Mansour, Ahmed Ibn,Rodriguez-Serrano, Fernando,Carrasco, Esther,Alvarez, Pablo Juan,Chahboun, Rachid,Alvarez-Manzaneda, Enrique
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p. 1026 - 1036
(2015/06/02)
-
- P2X4 RECEPTOR MODULATING COMPOUNDS AND METHODS OF USE THEREOF
-
Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.
- -
-
Paragraph 00211
(2015/06/25)
-
- BETA-SUBSTITUTED BETA-AMINO ACIDS AND ANALOGS AS CHEMOTHERAPEUTIC AGENTS
-
β-Substituted β-amino acids, β-substituted β-amino acid derivatives, and β-substituted β-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.
- -
-
Paragraph 0545; 0546; 0594
(2015/09/22)
-
- Stereoselective synthesis of quaternary carbons via the dianionic Ireland-Claisen rearrangement
-
A dianionic Ireland-Claisen rearrangement of chiral, nonracemic α-methyl-β-hydroxy allylic esters has been developed that proceeds with high diastereoselectivity and provides products containing three contiguous stereogenic carbons, including a quaternary center. The potential utility of the rearrangement for complex molecule synthesis is also demonstrated.
- Crimmins, Michael T.,Knight, John D.,Williams, Philip S.,Zhang, Yan
-
supporting information
p. 2458 - 2461
(2014/05/20)
-
- A formal synthesis of herboxidiene/GEX1A
-
A formal synthesis of herboxidiene/GEX 1A is described. This approach demonstrates successful application of the Prins cyclization for the construction of the tetrahydropyran core of the target molecule. The chirality of the side chain has been established through the Sharpless asymmetric dihydroxylation and Evan's alkylation. The olefin cross-metathesis was applied to couple both key fragments. Copyright
- Yadav, Jhillu S.,Reddy, G. Madhusudhan,Anjum, S. Rehana,Reddy, B. V. Subba
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p. 4389 - 4397
(2014/07/21)
-
- ω-alkynyl lipid surrogates for polyunsaturated fatty acids: Free radical and enzymatic oxidations
-
Lipid and lipid metabolite profiling are important parameters in understanding the pathogenesis of many diseases. Alkynylated polyunsaturated fatty acids are potentially useful probes for tracking the fate of fatty acid metabolites. The nonenzymatic and enzymatic oxidations of ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were compared to that of linoleic and arachidonic acid. There was no detectable difference in the primary products of nonenzymatic oxidation, which comprised cis,trans-hydroxy fatty acids. Similar hydroxy fatty acid products were formed when ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were reacted with lipoxygenase enzymes that introduce oxygen at different positions in the carbon chains. The rates of oxidation of ω-alkynylated fatty acids were reduced compared to those of the natural fatty acids. Cyclooxygenase-1 and -2 did not oxidize alkynyl linoleic but efficiently oxidized alkynyl arachidonic acid. The products were identified as alkynyl 11-hydroxy-eicosatetraenoic acid, alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid, and alkynyl prostaglandins. This deviation from the metabolic profile of arachidonic acid may limit the utility of alkynyl arachidonic acid in the tracking of cyclooxygenase-based lipid oxidation. The formation of alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid compared to alkynyl prostaglandins suggests that the ω-alkyne group causes a conformational change in the fatty acid bound to the enzyme, which reduces the efficiency of cyclization of dioxalanyl intermediates to endoperoxide intermediates. Overall, ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid appear to be metabolically competent surrogates for tracking the fate of polyunsaturated fatty acids when looking at models involving autoxidation and oxidation by lipoxygenases.
- Beavers, William N.,Serwa, Remigiusz,Shimozu, Yuki,Tallman, Keri A.,Vaught, Melissa,Dalvie, Esha D.,Marnett, Lawrence J.,Porter, Ned A.
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p. 11529 - 11539
(2014/10/15)
-
- SPIRO AZETIDINE ISOXAZOLE DERIVATIVES AND THEIR USE AS SSTR5 ANTAGONISTS
-
Provided is a compound represented by the following formula (1) or a salt thereof, which has an SSTR5 antagonistic action: wherein each symbol has the same definition as in the specification.
- -
-
Paragraph 1184
(2014/09/29)
-
- PDE 10a Inhibitors for the Treatment of Type II Diabetes
-
Disclosed are compounds, compositions and methods for treating Type II diabetes. Such compounds are represented by Formula (I) as follows: wherein R1, R2, L, and Q are defined herein.
- -
-
Paragraph 0927; 0928
(2015/01/06)
-
- 2 SUBSTITUTED CEPHEM COMPOUNDS
-
The compounds of formula (I) of the subject invention are related to 2-substituted cephem compounds, which have a wide antimicrobial spectrum, in particular exhibit potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and pharmaceutical compositions comprising the same.
- -
-
Paragraph 0292
(2014/05/24)
-
- Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists
-
We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.
- Chen, Jianyong,Levant, Beth,Jiang, Cheng,Keck, Thomas M.,Newman, Amy Hauck,Wang, Shaomeng
-
supporting information
p. 4962 - 4968
(2014/07/07)
-
- Synthesis of Cyclopropanated 7-Oxabenzonorbornadienes
-
Symmetrical and unsymmetrical 7-oxabenzonorbornadienes have been cyclopropanated using diazomethane gas under palladium catalysis. Good to excellent isolated yields (64-96%) of cyclopropanated oxabenzonorbornadienes were obtained, and excellent stereoselectivities were observed with exo-cyclopropanes as the only stereoisomeric products. Georg Thieme Verlag Stuttgart New York.
- McKee, Mary,Haner, Jamie,Carlson, Emily,Tam, William
-
p. 1518 - 1524
(2014/06/10)
-
- Continuous flow synthesis of β-amino acids from α-amino acids via Arndt-Eistert homologation
-
A fully continuous four step process for the preparation of β-amino acids from their corresponding α-amino acids utilizing the Arndt-Eistert homologation approach is described. the Partner Organisations 2014.
- Pinho, Vagner D.,Gutmann, Bernhard,Kappe, C. Oliver
-
p. 37419 - 37422
(2014/12/09)
-
- Complexation of chiral di (N-Protected α-Amino)-β-diketones with some transition metals
-
Chiral Di (N-protected a-amino)-b-diketones and its transition metal complexes have been synthesized. Di(N-protected a-amino)-b- diketones were prepared by reaction of activation of N-protected- a-amino acids (imidazolide) with a-diazoketones derived from natural amino acids in presence of lithium diisopropyl amid in tetrahydrofuran as a solvent at -78 °C and treatment the product with rhodium acetate to remove diazo group. The synthesized compounds were characterized by analytical techniques viz: IR, NMR and elemental analysis. The thermal stability of the newly synthesized metal complexes have been studied.
- Saraireh, Ibrahim A.M.
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p. 4747 - 4752
(2013/07/28)
-
- Synthesis and anti-cancer activity of some novel C-17 analogs of ursolic and oleanolic acids
-
A series of seventeen novel analogs of ursolic and oleanolic acid were synthesized (60-98 %), and evaluated for their anti-cancer potential against a panel of eight human cancer cell lines. Compounds (3-10) showed comparable or better activities than their respective parent compounds against SiHa and HeLa (Cervix), A-549 (Lung), and IMR-32 (Neuroblastoma) cancer cell lines. Significantly, among the bromoalkyl esters (11-19), compound 13 showed promising anti-cancer activity against Leukemia THP-1 cell line at 10 μM concentration. In this series, it is interesting to note that the increase in chain length has an adverse effect on the activity.
- Mallavadhani, Uppuluri V.,Mahapatra, Anita,Pattnaik, Banita,Vanga, Nagireddy,Suri, Nitasha,Saxena, Ajit K.
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p. 1263 - 1269
(2013/04/10)
-
- Stereoselective total synthesis of (-)-batzellasides a, b, and c
-
Total synthesis of (-)-L-batzellasides A, B, and C has been achieved in 13 steps from known lactone 2 in 12.6, 13.2, and 13.8 % overall yields, respectively. The key steps in this synthesis were the stereoselective introduction of an allyl group at the C1
- Okaki, Toru,Fujimura, Ryohei,Sekiguchi, Masataka,Zhou, Dejun,Sugimoto, Kenji,Minato, Daishiro,Matsuya, Yuji,Kato, Atsushi,Adachi, Isao,Tezuka, Yasuhiro,Saporito, Ralph A.,Toyooka, Naoki
-
p. 2841 - 2848
(2013/07/11)
-
- Functionally substituted Schiff bases in reduction reactions
-
Functionally substituted Schiff bases obtained by the condensation of nitroaniline, pyrimidinylaminoaniline, 5-aminoquinoline, 5-aminoquinaldine derivatives with 4-methylformylbenzoate were studied in the reactions of sodium borohydride with acidic activators, hydrazine hydrate in the presence of Raney nickel, Raney alloy in the presence of potassium hydroxide. By the reduction of azomethines new benzyl derivatives of aniline, quinolylamine, arylaminopyrimidine, and phenylenediamine were obtained.
- Koroleva,Gusak,Ignatovich,Ermolinskaya
-
p. 212 - 220
(2013/07/25)
-
- Chemoenzymatic preparation of (6R)-5,6-dihydro-2H-pyran-2-one: A ubiquitous structural motif of biologically active lactones
-
A chemoenzymatic synthesis of an enantiopure 6-substituted 5,6-dihydro-2H-pyran-2-one using bromobenzene as a starting material is presented. This important structural motif is found in a large number of chiral lactones that present a wide range of biological activities. The key features of the preparation include enzymatic dioxygenation of bromobenzene using Escherichia coli JM109 (pDTG601), microwave-assisted acyloin cleavage, and tin mediated lactonization. The stereochemical assignment for the alcohol was confirmed by NMR analysis of Moshers derivatives.
- Carrera, Ignacio,Brovetto, Margarita,Seoane, Gustavo A.
-
p. 1467 - 1472
(2013/12/04)
-
- COMPLEMENT PATHWAY MODULATORS AND USES THEREOF
-
The present invention provides a compound of formula I a method for manufacturing the compounds of the invention, and its therapeutic uses as inhibitor of the complement alternative pathway and particularly as inhibitor of Factor B for the treatment of e.g. age-related macular degeneration and diabetic retinopathy. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
- -
-
Page/Page column 87
(2014/01/09)
-
- A METHOD FOR THE PREPARATION OF DIAZOALKANES
-
The present invention relates to a method of forming diazoalkanes. One aspect of the present invention provides a method for the production of a N-alkyl-N-nitroso compound from a starting material, comprising the use of a tribasic acid to acidify an amine. A second aspect of the present invention provides a method for the production of a diazoalkane, comprising reacting a N-alkyl-N-nitroso compound with a base and a phase transfer catalyst, wherein no organic solvent is used,
- -
-
Page/Page column 16
(2013/08/15)
-
- Synthesis of new N-(arylcyclopropyl)acetamides and N-(arylvinyl)acetamides as conformationally-restricted ligands for melatonin receptors
-
N-(Arylcyclopropyl)acetamides and N-(arylvinyl)acetamides or methyl ureas have been prepared as constrained analogues of melatonin. The affinity of these new compounds for chicken brain melatonin receptors and recombinant human MT1 and MT2 receptors was evaluated using 2-[ 125I]-iodomelatonin as radioligand. Strict ethylenic or cyclopropyl analogues of the commercialized agonist agomelatine (Valdoxan) were equipotent to agomelatine in binding bioassays. However, the ethylenic analogue was more effective than the cyclopropyl one in the melanophore aggregation bioassay, but was still less potent than the disubstituted 2,7-dimethoxy- naphtalenic compounds.
- Morellato, Laurence,Lefas-Le Gall, Marie,Langlois, Michel,Caignard, Daniel-Henri,Renard, Pierre,Delagrange, Philippe,Mathe-Allainmat, Monique
-
supporting information
p. 430 - 434
(2013/02/23)
-
- 3-Trimethylsilylcyclobutylidene. the γ-effect of silicon on carbenes
-
3-Trimethylsilylcyclobutylidene was generated by pyrolysis of the sodium salt of the tosylhydrazone derivative of 3-trimethylsilylcyclobutanone. This carbene converts to 1-trimethylsilylbicyclobutane as the major product. A labeling study shows that this intramolecular rearrangement product comes from 1,3-hydrogen migration to the carbenic center and not 1,3-silyl migration. Computational studies show two carbene minimum energy conformations, with the lower energy conformation displaying a large stabilizing interaction of the carbene center with the rear lobe of the C3-Si bond. In this conformation, the trimethylsilyl group cannot migrate to the carbene center, and the most favorable process is 1,3-hydrogen migration. When the carbene is generated photochemically in methanol, it reacts by a protonation mechanism giving the highly stabilized 3-trimethylsilylcyclobutyl carbocation as an intermediate. When generated in dimethylamine as solvent, the carbene undergoes preferred attack of this nucleophilic solvent from the back of this C-Si rear lobe stabilized carbene.
- Creary, Xavier
-
p. 6570 - 6578
(2013/06/26)
-
- Cycloalkane carboxylic acid derivatives as CXCR3 receptor antagonists
-
The present invention relates to compounds of formula 1 that are useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of diseases caused by abnormal activation of CXCR3 chemokines. The invention relates furthermore to a process for the preparation of said compounds, to pharmaceutical compositions containing said compounds and to the novel intermediates used in the preparation of said compounds.
- -
-
Paragraph 0090; 0091
(2013/06/27)
-
- Amination of phenylketene revisit. Substituent effect on reactivity
-
The asymmetric stretching frequencies of the ketene group of the m,p-substituted phenylketenes were found to be correlated with σ The substituent effects for the second-order rate constants of phenylketenes with various amines were not correlated linearly
- Badal, Md. Mizanur Rahman,Zhang, Min,Kobayashi, Shinjiro,Mishima, Masaaki
-
p. 856 - 863
(2013/08/15)
-