- Synthetic studies toward longeracemine: a SmI2-mediated spirocyclization and rearrangement cascade to construct the 2-azabicyclo[2.2.1]heptane framework
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Longeracemine, a member of theDaphniphyllumfamily of alkaloids contains a novel carbon framework featuring a highly functionalized 2-azabicyclo[2.2.1]heptane core as part of an overall 5/6/5/5/6/5 skeleton. A synthetic intermediate containing the core of longeracemine has been efficiently prepared by employing a stereoselective SmI2-mediated cascade reaction to advance a 7-azabicyclo[2.2.1]heptadiene to a 2-azabicyclo[2.2.1]heptene that is functionally poised for conversion to the natural product.
- Cox, Joshua B.,Komine, Keita,Lambert, Kyle M.,Savage, Quentin R.,Wood, John L.
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Read Online
- METHOD OF PRODUCING CYANOALDEHYDE COMPOUND
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PROBLEM TO BE SOLVED: To provide a method of producing a cyanoaldehyde compound by reaction in the presence of a heterogeneous catalyst. SOLUTION: In the method of producing a cyanoaldehyde compound, a gas mixture containing hydrogen gas and carbon monoxide gas is reacted with an unsaturated nitrile compound represented by the formula (1) in the figure in the presence of a heterogeneous catalyst in which a Group 8-11 metal or metal oxide of the fifth or sixth period of the periodic table is supported by a support comprising an oxide of a Group 4-14 element of the fourth period of the periodic table. (In the formula (1), R1 and R2 are each selected from among a hydrogen atom, a C1-8 alkyl group, a cyclohexyl group and a phenyl group.) SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
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Paragraph 0039-0046
(2020/12/15)
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- Photocatalytic Reductive Radical-Polar Crossover for a Base-Free Corey–Seebach Reaction
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A metal-free generation of carbanion nucleophiles is of prime importance in organic synthesis. Herein we report a photocatalytic approach to the Corey–Seebach reaction. The presented method operates under mild redox-neutral and base-free conditions giving the desired product with high functional group tolerance. The reaction is enabled by the combination of photo- and hydrogen atom transfer (HAT) catalysis. This catalytic merger allows a C?H to carbanion activation by the abstraction of a hydrogen atom followed by radical reduction. The generated nucleophilic intermediate is then capable of adding to carbonyl electrophiles. The obtained dithiane can be easily converted to the valuable α-hydroxy carbonyl in a subsequent step. The proposed reaction mechanism is supported by emission quenching, radical–radical homocoupling and deuterium labeling studies as well as by calculated redox-potentials and bond strengths.
- Crespi, Stefano,Donabauer, Karsten,K?nig, Burkhard,Murugesan, Kathiravan,Rozman, Ur?a
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supporting information
p. 12945 - 12950
(2020/09/23)
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- Multicomponent Catalytic Asymmetric Synthesis of trans-Aziridines
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A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound. A variety of 11 different electron-poor and electron-rich aryl aldehydes were screened to give trans-aziridines in 73-90% yield with 82-99% ee and trans/cis selectivities of 19:1 to >99:1. The optimal protocol for the trans-aziridination of aliphatic aldehydes did not require prereaction of the catalyst, aldehyde, and amine, and instead, the diazo compound could be added directly. The scope of the reaction is limited to unbranched aliphatic aldehydes and was tolerant of a number of functional groups including ethers, esters, epoxides, carbamates, and phthalimides. A total of 10 aliphatic aldehydes were examined and found to give trans-aziridines in 60-88% yield with 60-98% ee and trans/cis selectivities of 6:1 to >99:1. Alkenyl aldehydes did not react, but an alkynyl aldehyde gave a 71% yield and 95% ee of an aziridine that was found to be the cis- and not the trans-diastereomer. The aryl and aliphatic aldehydes both gave the trans-aziridines with the same absolute configuration with the same catalyst; however, in those cases where cis-aziridines were formed, the configuration was opposite for those formed from aryl versus aliphatic aldehydes.
- Zhou, Yubai,Gupta, Anil K.,Mukherjee, Munmun,Zheng, Li,Wulff, William D.
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p. 13121 - 13140
(2017/12/26)
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- Evolution of an oxidative dearomatization enabled total synthesis of vinigrol
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The evolution of the synthetic strategy resulting in a total synthesis of vinigrol is presented. Oxidative dearomatization/intramolecular Diels-Alder cycloaddition has served as the successful cornerstone for all of the approaches. Extensive radical cyclization efforts to form the tetracyclic core resulted in interesting and surprising reaction outcomes, none of which could be advanced to vinigrol. These cyclization obstacles were successfully overcome by using Heck instead of radical cyclizations. The total synthesis features a trifluoroethyl ether protecting group being used for the first time in organic synthesis. The logic of its selection and the group's importance beyond protecting the C8a hydroxyl group is presented along with a discussion of strategies for its removal. Because of the compact tetracyclic cage the route is built around many unusual reaction observations and solutions have emerged. For example, a first of its kind Grob fragmentation reaction featuring a trifluoroethyl leaving group has been uncovered, interesting interrupted selenium dioxide allylic oxidations have been observed as well as intriguing catalyst and counterion dependent directed hydrogenations.
- Yang, Qingliang,Draghici, Cristian,Njardarson, Jon T.,Li, Fang,Smith, Brandon R.,Das, Pradipta
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supporting information
p. 330 - 344
(2014/01/06)
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- A modular synthesis of teraryl-based α-helix mimetics, part 2: Synthesis of 5-pyridine boronic acid pinacol ester building blocks with amino acid side chains in 3-position
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One of the most common protein-protein interactions (PPI) is the interaction of the α-helix of one protein with the surface of the second one. Terphenylic scaffolds are bioinspired motifs in the inhibition of PPIs and have been identified as suitable α-helix mimetics. One of the challenging aspects of this strategy is the poor solubility of terphenyls under physiological conditions. In the literature pyrrolopyrimidine-, pyrimidine- or pyridazine-based mimetics have been reported to show improved solubility. We present a new convergent strategy for the synthesis of linear pyridine-type teraryls based on a phenylic core unit. A general approach for the synthesis of 3,5-disubstituted pyridine-based boronic acid pinacol esters with amino acid side chains in the 3-position (representing Phe, Leu, Ile, Lys, Asp, Asn) is presented and exploits the functional group tolerance of the Knochel-Grignard reagents. The building blocks have been used in a convergent in situ two-step synthesis of teraryl α-helix mimetics. Tune in: The chemical orthogonality of Knochel's Grignard chemistry enables the synthesis of 3-substituted 5-pyridine-boronic esters with amino acid side chains, which can be used for convenient assembly of teraryl-based α-helix peptide mimetics by Suzuki coupling (see scheme; dppf=1,1′-bis(diphenylphosphino)ferrocene, DME= dimethoxyethane, Tf=trifluoromethanesulfonyl). Copyright
- Peters, Martin,Trobe, Melanie,Breinbauer, Rolf
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supporting information
p. 2450 - 2456
(2013/03/28)
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- Biobased synthesis of acrylonitrile from glutamic acid
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Glutamic acid was transformed into acrylonitrile in a two step procedure involving an oxidative decarboxylation in water to 3-cyanopropanoic acid followed by a decarbonylation-elimination reaction using a palladium catalyst. The Royal Society of Chemistry.
- Le Notre, Jerome,Scott, Elinor L.,Franssen, Maurice C. R.,Sanders, Johan P. M.
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supporting information; experimental part
p. 807 - 809
(2011/06/22)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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The present application relates to isothiazolylidene containing compounds of Formula (I) wherein R1, R2, R3, R4, and L are as defined in the specification, compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions.
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Page/Page column 72
(2010/06/11)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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The present application relates to isothiazolylidene containing compounds of Formula (I) wherein R1, R2, R3, R4, and L are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 56
(2008/12/08)
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- Modular chiral bidentate phosphonites: Design, synthesis, and application in catalytic asymmetric hydroformylation reactions
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A new class of C2-symmetric chiral bidentate phosphonite ligands has been synthesized in moderate to good yields from readily available starting materials. Application of these air-stable chiral phosphonites in the Rh I-catalyzed asymmetric hydroformylation of styrene derivatives, vinyl acetate, and allyl cyanide afforded the corresponding chiral aldehydes with high regio- and enantioselectivities under mild reaction conditions. The modular nature of the ligands allows fine-tuning of the selectivities through judicious modifications of the substituents on the ligand backbone. X-ray structural analysis of the catalyst precursor suggested that the steric hindrance caused by the protruding remote substituents of the ligands into the vicinity of the metal center might be an important factor for the enantio-control of the reaction, whereas the sense of asymmetric induction can be rationalized on the basis of a trigonal-bipyramidal transition state diagram.
- Zhao, Baoguo,Peng, Xingao,Wang, Zheng,Xia, Chungu,Ding, Kuiling
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experimental part
p. 7847 - 7857
(2009/11/30)
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- VIGABATRIN BIOISOTERES AND RELATED METHODS OF USE
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Compounds bioisoteric to vigabatrin and related methods of use.
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Page/Page column 9; 15-16
(2010/11/26)
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- New substrates and inhibitors of γ-aminobutyric acid aminotransferase containing bioisosteres of the carboxylic acid group: Design, synthesis, and biological activity
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A series of potential substrates of γ-aminobutyric acid aminotransferase (GABA-AT) with lipophilic bioisosteres of the carboxylic acid group (2-7) were synthesized and tested. Most of the synthesized compounds showed substrate activities with GABA-AT; 1H-tetrazole-5-propanamine (6) was the best of those tested. The potential time-dependent inhibitor of GABA-AT, 1H-tetrazole-5-(α-vinyl-propanamine) (8), was designed based on the structures of 6 and the antiepilepsy drug vigabatrin (4-aminohex-5-enoic acid, 1). The synthesized compound 8 showed time-dependent inhibition of GABA-AT, but its potency is lower than that of vigabatrin. Methylation of the tetrazole group in 8 resulted in loss of time-dependent activity, suggesting that the tetrazole ring, the carboxylate bioisostere, exists in its deprotonated form in the enzyme active site.
- Yuan, Hai,Silverman, Richard B.
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p. 1331 - 1338
(2007/10/03)
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- Copper-Catalyzed Tandem Conjugate Addition-Electrophilic Trapping: Ketones, Esters, and Nitriles as Terminal Electrophiles
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Exposure of enone substrates 1a?18a, which possess appendant ketone, ester, and nitrile moieties, to Et2Zn in the presence of catalytic Cu(OTf)2/P(OEt)3 provides the cyclized products in good to excellent yields and diastereoselectivities. These results represent the first use of ketones, esters, and nitriles as terminal electrophiles in Cu-catalyzed conjugate addition?electrophilic trapping. Copyright
- Agapiou, Kyriacos,Cauble, David F.,Krische, Michael J.
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p. 4528 - 4529
(2007/10/03)
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- New synthesis of a pyrroloquinoline skeleton, the martinelline core, using a tandem Michael-aldol strategy
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The pyrroloquinoline moiety of Martinelline, a naturally occurring bradykinin receptor antagonist, has been synthesized from 1,2-dihydroquinoline which was prepared by using a tandem Michael-aldol reaction as a key step.
- Hara, Osamu,Sugimoto, Kazuhiko,Makino, Kazuishi,Hamada, Yasumasa
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p. 1625 - 1627
(2007/10/03)
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- Preparation of [1,2,3,4,5-13C 5]-5-Amino-4-oxopentanoic Acid (ALA) - Design of a Synthetic Scheme to Prepare Any 13C- and 15N-Isotopomer with High Isotopic Enrichment
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5-Amino-4-oxopentanoic acid (5-aminolevulinic acid) is a precursor in the biosynthesis of the biologically active porphyrins such as chlorophyll, bacteriochlorophyll, heme, etc. These systems are central in photosynthesis, oxygen transport, electron transport, etc. In this paper we describe a simple scheme to prepare any isotopomer of 5-aminolevulinic acid in a few steps in high yield. Using a similar scheme, levulinic acid can now also be prepared in any isotopomeric form. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Shrestha-Dawadi, Prativa Bade,Lugtenburg, Johan
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p. 4654 - 4663
(2007/10/03)
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- Deoxyhypusine reagent and peptides
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The invention relates to a method and reagent for the synthesis of peptides containing deoxyhypusine, the reagent having the formula: wherein: Q1and Q2may be the same or different and are amino protective groups, and Q3is an amino protective group which is orthogonal to Q1and Q2. The invention also relates to peptides of formula S-deoxyHpu-T??(2) that may be synthesized using the reagent of the invention, wherein deoxyHpu is the deoxyhypusine residue, S and T are each independently peptide residues from zero to 12 amino acids in length.
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- Synthesis of reagents for the construction of hypusine and deoxyhypusine peptides and their application as peptidic antigens
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Two new synthetic methods which allow access to (2S)-deoxyhypusine, natural (2S,9R)-hypusine, (2S,9S)-hypusine, and deoxyhypusine- and hypusine- containing peptides are described. The methods involve both the construction of a deoxyhypusine reagent in which the α-nitrogen protecting group is orthogonal to the N-7 and N-12 protecting groups and an alternate synthesis of our previous hypusine reagent, a synthesis which provides for better stereochemical control at C-9. Synthetic hypusine and deoxyhypusine can be generated from these reagents. The hypusine-containing hexapeptide (Cys-Thr- Gly-Hpu-His-Gly) is conjugated to ovalbumin (OVA), keyhole limpet hemocyanin (KLH), and a bis-maleimide; KLH conjugates are also made with the deoxyhypusine- and lysine-containing hexapeptides. Monoclonal antibodies are generated to the hypusine-containing hexapeptide-OVA conjugate in mice. These are isolated and screened against the hypusine-containing hexapeptide-KLH and hypusine-containing hexapeptide-bis-maleimide conjugates, as well as against the deoxyhypusine-containing and lysine-containing hexapeptide-KLH conjugates. These antibodies may be useful in localizing intracellular hypusine-containing peptides as well as peptides containing hypusine analogues.
- Bergeron, Raymond J.,Weimar, William R.,Müller, Ralf,Zimmerman, Curt O.,McCosar, Bruce H.,Yao, Hua,Smith, Richard E.
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p. 3888 - 3900
(2007/10/03)
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- Method and compounds for diagnosing coronary artery disease
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The present invention relates generally to methods of diagnosis, evaluation and treatment of coronary artery disease in mammals using substituted catecholamines and compounds therefore. It also relates to the preparation, use and administration of these compounds which are useful in the diagnosis, evaluation and treatment of coronary artery disease by means of a feedback controlled drug delivery system that delivers exercise simulating agents which are capable of eliciting acute responses similar to those elicited by aerobic exercise.
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- RESISTANCE OF ACRYLONITRILE AND OF ITS HYDROFORMYLATION PRODUCTS TO THERMAL AND CATALYTIC ACTION.
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The study of the resistance of acrylonitrile and its hydroformylation products to thermal and catalytic action showed that at 120 degree and 30 MPa pressure in presence of cobalt carbonyls acrylonitrile does not undergo polymerization in presence of an inhibitor (hydroquinone); beta -cyanopropionaldehyde and its dimethyl acetal are stable when the process is conducted in methanol, but in nonpolar solvents (benzene) beta -cyanopropionaldehyde polymerizes. The use of methanol during storage and oxidative treatment of the products of acrylonitrile hydroformylation stabilizes beta -cyanopropionaldehyde.
- Del'nik,Kagna,Katsnel'son,Leenson
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p. 1248 - 1251
(2007/10/02)
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- FORMATION OF THE ACETAL OF beta -CYANOPROPIONALDEHYDE IN THE PRESENCE OF COBALT CARBONYLS.
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As a result of a study of the acetalization of beta -cyanopropionaldehyde with methyl alcohol at various molar ratios in the presence of cobalt carbonyls and under typical conditions for the hydroformylation of acrylonitrile, the equilibrium constants of the acetalization reaction have been determined. It has been shown that to obtain predominant conversion of beta -cyanopropionaldehyde into the diacetal during the hydroformylation, the initial acrylonitrile concentration should be 10-20 wt. %. A retarding effect by acrylonitrile on the acetalization of beta -cyanoproprionaldehyde, under the conditions of the hydroformylation reaction, has been detected.
- Katsnel'son,Del'nik,Kagna,Leenson
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p. 2514 - 2517
(2007/10/02)
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- C-5-Substituted Pyrimidine Nucleosides. 3. Reaction of Allylic Chlorides, Alcohols, and Acetates with Pyrimidine Nucleoside Derived Organopalladium Intermediates
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The reaction of allylic chlorides with pyrimidine nucleoside derived organopalladium intermediates was investigated.The organopalladium intermediates were generated in situ by the reaction of 5-(chloromercuri)-2'-deoxyuridine (1), 5-(chloromercuri)cytidine, and 5-(chloromercuri)-2'-deoxycytidine with a catalytic amount of Li2PdCl4 in methanol.With allyl chloride, 1 gives principally 5-allyl-2'-deoxyuridine, some of which reacts further with 1 to give the cross-linked nucleosides (E)-5--2'-deoxyuridine (5) and5--2'-deoxyuridine (6). 3-Chloro-1-butene couples with 1 to give mainly (E)-5-(2-buten-1-yl)-2'-deoxyuridine (9) and lesser amounts of the Z isomer 10 and 5-(1-methyl-2-propen-1-yl)-2'-deoxyuridine (11).Nucleoside 11 appears to be the product of a coupling reaction between 1-methoxy-2-butene and the organopalladium intermediate derived from 1.Allylic chlorides are transformed to allyl methyl ethers in 0.1 M Li2PdCl4 at a slightly slower rate than the coupling reaction.Higher allylic chloride homologues show greater regioselectivity and stereoselectivity. 3-Chloro-1-pentene leads to (E)-5-(2-penten-1-yl)-2'-deoxyuridine (14) as the sole major product in 50percent yield.When a cyano group was attached to C-5 of 3-chloro-1-pentene, the resultant allylic chloride coupled regioselectivity but gave both cis and trans isomers.The mechanism of the coupling reaction is discussed and a basis for stereoselectivity proposed.Allylic alcohols and acetates couple more slowly and less cleanly, leading to lower yields of the same allylic-substituted pyrimidine nucleosides obtained with allylic chlorides.In some instances other products could be isolated.Nucleoside 1 and 3-hydroxy-4-methyl-1-pentene gave 5-(4-methyl-2-penten-1-yl)-2'-deoxyuridine (16) as well as 5-(4-methyl-3-oxopentyl)-2'-deoxyuridine (20). 3-Acetoxy-4-methyl-1-pentene led to (E)-5-(4-methyl-1,3-pentadien-1-yl)-2'-deoxyuridine (23).Mechanisms leading to these products are discussed.
- Bergstrom, Donald E.,Ruth, Jerry L.,Warwick, Paul
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p. 1432 - 1441
(2007/10/02)
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