- Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots
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The thread-link-cut (TLC) approach has previously shown promise as a novel method to synthesize molecular knots. The modular second-generation approach to small trefoil knots described herein involves electrostatic interactions between an electron-rich bismacrocyclic host compound and electron-deficient guests in the threading step. The bis-macrocyclic host was synthesized in eight steps and 6.6% overall yield. Ammonium and pyridinium guests were synthesized in 4-5 steps. The TLC knot-forming sequence was carried out and produced a product with the expected molecular weight, but, unfortunately, further characterization did not produce conclusive results regarding the topology of the product.
- Fenlon, Edward E.,Keyes, Rebecca J.,Lockey, Stephen D.,Margolis, Elizabeth A.
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- ENVIRONMENTALLY-FRIENDLY HYDROAZIDATION OF OLEFINS
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The present invention provides processes for the synthesis of organic azides, intermediates for the production thereof, and compositions related thereto.
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Page/Page column 63; 74-75; 79-80
(2020/01/24)
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- Direct Intermolecular Anti-Markovnikov Hydroazidation of Unactivated Olefins
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We herein report a direct intermolecular anti-Markovnikov hydroazidation method for unactivated olefins, which is promoted by a catalytic amount of bench-stable benziodoxole at ambient temperature. This method facilitates previously difficult, direct addition of hydrazoic acid across a wide variety of unactivated olefins in both complex molecules and unfunctionalized commodity chemicals. It conveniently fills a synthetic chemistry gap of existing olefin hydroazidation procedures, and thereby provides a valuable tool for azido-group labeling in organic synthesis and chemical biology studies.
- Li, Hongze,Shen, Shou-Jie,Zhu, Cheng-Liang,Xu, Hao
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supporting information
p. 9415 - 9421
(2019/06/21)
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- Copper-catalyzed cascade click/nucleophilic substitution reaction to access fully substituted triazolyl-organosulfurs
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A novel cascade click/nucleophilic substitution reaction is developed to access 4-heterofunctionalized fully substituted triazolyl-organosulfurs using thiocyanates as both leaving groups and organosulfur precursors. This method features high regioselectivities and board substrate scope. 33 examples are shown to demonstrate the structural diversity through the synthesis of fully substituted triazolyl-organosulfurs including triazolyl-thiocyanates, triazolyl-sulfinylcyanides, triazolyl-thioethers, triazolyl-thiols and triazolyl-disulfides from internal thiocyanatoalkynes.
- Li, Ming,Dong, Kun,Zheng, Yubin,Song, Wangze
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supporting information
p. 9933 - 9941
(2019/12/06)
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- Traceless Templated Amide-Forming Ligations
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Template assistance allows organic reactions to occur under highly dilute conditions - where intermolecular reactions often fail to proceed - by bringing reactants into close spatial proximity. This strategy has been elegantly applied to numerous systems, but always with the retention of at least one of the templating groups in the product. In this report, we describe a traceless, templated amide-forming ligation that proceeds at low micromolar concentration under aqueous conditions in the presence of biomolecules. We utilized the unique features of an acylboronate-hydroxylamine ligation, in which covalent bonds are broken in each of the reactants as the new amide bond is formed. By using streptavidin as a template and acylboronates and O-acylhydroxylamines bearing desthiobiotins that are cleaved upon amide formation, we demonstrate that traceless, templated ligation occurs rapidly even at submicromolar concentrations. The requirement for a close spatial orientation of the functional groups - achieved upon binding to streptavidin - is critical for the observed enhancement in the rate and quantity of product formed.
- Osuna Gálvez, Alberto,Bode, Jeffrey W.
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supporting information
p. 8721 - 8726
(2019/06/13)
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- Rhodium(I)-Catalyzed Regioselective Azide-internal Alkynyl Trifluoromethyl Sulfide Cycloaddition and Azide-internal Thioalkyne Cycloaddition under Mild Conditions
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A regioselective method to access fully substituted 5-trifluoromethylthio-1,2,3-triazoles and 5-thio-1,2,3-triazoles from the internal alkynyl trifluoromethyl sulfides and internal thioalkynes by a rhodium(I)-catalyzed azide-alkyne cycloaddition (RhAAC) reaction under mild conditions has been developed. This approach features good compatibility with water and air, a broad substrate scope, good functional group tolerance, high yields and excellent regioselectivities. The high 1,5-regioselectivities were controlled by the strong coordination between the sulfur atom and the π-acidic rhodium. The advantages of this method further include its applicability to gram-scale preparation, the use of solid-phase synthesis technique, and the mutually orthogonal CuAAC-RhAAC reaction. (Figure presented.).
- Song, Wangze,Zheng, Nan,Li, Ming,He, Junnan,Li, Junhao,Dong, Kun,Ullah, Karim,Zheng, Yubin
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supporting information
p. 469 - 475
(2019/01/04)
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- Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity
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Phthalimido-alkyl-1H-1,2,3-triazole derivatives 3a–d and 4a–d were efficiently synthesized using 1,3-di-polar cycloaddition reaction. Anti-inflammatory activity and toxicity studies were performed. The results demonstrated that all the tested compounds reduced carrageenan-induced paw edema and indicated no lethality for toxicity against Artemia salina and acute toxicity in vivo (LD50 up to 1gkg ?1). Furthermore, the structure of phthalimide linked to phenyl group proved to be more active than the compounds containing benzothiazole moiety. Structural modifications such as removal of the phthalimide group and subsequent acetylation, to exemplify a non-cyclic amide, demonstrate that the phthalimide and triazole moieties are important for design of potent candidates with anti-inflammatory drug proprieties. Docking into the cyclooxy-genase-2 (COX-2) confirms the importance of the phthalimide and triazole groups in the anti-inflammatory activity. The histopathological studies showed that the compounds 3a–d and 4a–d did not cause serious pathological lesions liver or kidneys.
- Assis, Shalom P. De O.,Da Silva, Moara T.,Da Silva, Filipe Torres,Sant’Anna, Mirella P.,De Albuquerque Tenório, Carolina M.B.,Brito Dos Santos, Caroline F.,Da Fonseca, Caíque S.M.,Seabra, Gustavo,Lima, Vera L.M.,De Oliveira, Ronaldo N.
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- Palladium-Catalyzed Annulation of Aryltriazoles and Arylisoxazoles with Alkynes
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We developed herein a palladium-catalyzed annulation of aryltriazoles and arylisoxazoles with internal alkynes via C?H bond activation process. 4,5-disubstituted-3H-naphtho[1,2-d][1,2,3]triazoles and 4,5-disubstituted-naphtho[2,1-d]isoxazoles could be afforded in good yields, respectively. The starting materials are readily available and the scope and applications of this transformation were explored. The reaction offers a practical approach to naphthalene fused heterocycles. (Figure presented.).
- Yuan, Hairui,Wang, Min,Xu, Zhenghu,Gao, Hongyin
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supporting information
p. 4386 - 4392
(2019/08/12)
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- Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals)
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Here we report the development of a proteolysis targeting chimera (PROTAC) based on the combination of the unique features of the sirtuin rearranging ligands (SirReals) as highly potent and isotype-selective Sirt2 inhibitors with thalidomide, a bona fide
- Schiedel, Matthias,Herp, Daniel,Hammelmann, S?ren,Swyter, S?ren,Lehotzky, Attila,Robaa, Dina,Oláh, Judit,Ovádi, Judit,Sippl, Wolfgang,Jung, Manfred
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p. 482 - 491
(2018/02/07)
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- Rhodium(I)-Catalyzed Azide-Alkyne Cycloaddition (RhAAC) of Internal Alkynylphosphonates with High Regioselectivities under Mild Conditions
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A regioselective method to access fully substituted 1,2,3-triazolyl-4-phosphonates from the internal alkynylphosphonates by rhodium(I)-catalyzed azide-alkyne cycloaddition (RhAAC) under mild conditions is reported. This approach is water and air compatible and has a broad substrate scope, good functional group tolerance, high yields and excellent regioselectivities. Fully substituted 1,2,3-triazolyl-4-phosphonates are directly prepared from the internal alkynylphosphonates by RhAAC with high 1,4-regioselectivities. The gram-scale preparation, application to carbohydrate synthesis and the solid-phase synthesis of triazolyl-4-phosphonates are highlights of this method. (Figure presented.).
- Song, Wangze,Zheng, Nan,Li, Ming,Ullah, Karim,Zheng, Yubin
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supporting information
p. 2429 - 2434
(2018/05/30)
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- A NOVEL SYNTHETIC PATHWAY TOWARDS SOLITHROMYCIN AND PURIFICATION THEREOF
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The present invention relates to an efficient route of synthesis of solithromycin and to a method of its purification which obviates the necessity of chromatographic purifications and improves the quality of the product by efficiently removing impurities.
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- Iridium-Catalyzed Highly Regioselective Azide-Ynamide Cycloaddition to Access 5-Amido Fully Substituted 1,2,3-Triazoles under Mild, Air, Aqueous, and Bioorthogonal Conditions
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A highly regioselective method to access 5-amido fully substituted 1,2,3-triazoles by iridium-catalyzed azide-ynamide cycloaddition under mild, air, aqueous, and bioorthogonal conditions is reported. The excellent regioselectivities may derive from the strong coordination between the carbonyl oxygen of ynamide and the -acidic iridium. Since the iridium ion is insensitive to oxygen/water and exhibits low cytotoxicity, it could catalyze this reaction in both organic and biological environments efficiently. Preparation in gram-scale and application in carbohydrates highlight this method.
- Song, Wangze,Zheng, Nan
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supporting information
p. 6200 - 6203
(2017/11/24)
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- New strategies for molecular diversification of 2-[Aminoalkyl-(1H-1,2,3-Triazol-1- yl)]-1,4-naphthoquinones using click chemistry
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Click chemistry-based strategies for the synthesis of 2-Amino-Alkyl-1,2,3-Triazole-1,4- naphthoquinone derivatives make it possible to obtain desired products from 1,4-naphthoquinone (1,4-NQ), and bio-based lawsone, nor-lapachol and lapachol. The first route (Strategy A) starting from 1,4-NQ and amino alcohols, then 2-Amino-Alkyl-1,4-NQ alcohols, were tosylated. The azide ion displaced the tosylate group to afford 2-Azide-Alkyl-1,4-NQ, which was submitted to a copper-catalyzed azide alkyne cycloaddition (CuAAC) condition. The triazole-naphthoquinones were obtained in an overall yield of roughly 47percent. Another pathway (Strategy B) substituted bromo-Alkyl-phthalimides using NaN3 as the nucleophile, sequential CuAAC and deprotection of phthalimide group with hydrazine producing amino-Triazoles. The subsequent reaction with 1,4-NQ produced 2-Amino-Alkyl-1,2,3-Triazole-1,4-NQ derivatives in an overall yield of 45-76percent in four steps. After we developed these two strategies, linear synthesis (Strategy A) was chosen to prepare 2-[(2-(1H-1,2,3-Triazol-1-yl)ethylamino)]-3-(3-methylpropenyl)-1,4-naphthoquinones from lawsone with an overall yield of approximately 27percent in six steps. On the other hand, convergent synthesis (Strategy B) was employed for the synthesis of 2-[(4-phenyl-1H-1,2,3-Triazol-1-yl)alkyl-Amino)]-3-(3-methylbut-2-en-1-yl)-1,4-naphthoquinones from the reaction between 2-methoxy-lapachol with amino-Triazoles with a global yield of about 21percent. These synthetic strategies might lead us to new opportunities to build small-molecule libraries for future biological exploration.
- De Oliveira, Ronaldo N.,Da Silva, Mauro G.,Da Silva, Moara Targino,Melo, Valentina N.,Valen?a, Wagner O.,Da Paz, Josinete Angela,Camara, Celso A.
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p. 681 - 688
(2017/03/11)
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- Synthesis of new hybrid heterocyclic compounds having 1,2,3-triazole and isoxazole via click chemistry
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A simple and highly efficient method for the regioselective synthesis of isoxazolyl-1,4-disubstituted-1,2,3-triazoles 6a-l in good to excellent yields from terminal alkynes having isoxazole scaffold 4a-c and various azides through Cu(I)-catalyzed 1,3-dipolar cycloaddition is described. The reaction proceeds smoothly in 1:1 mixture of t-BuOH and water at RT. The structures of all newly synthesized hybrid heterocycles are established on the basis of spectral data ir, 1H nmr, mass, and elemental analysis.
- Jayaprakash Rao,Srinivas
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p. 1675 - 1678
(2015/01/09)
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- Design and synthesis of novel 2H-chromen-2-one derivatives bearing 1,2,3-triazole moiety as lead antimicrobials
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A series of novel 2H-chromen-2-one derivatives decorated with 1,2,3-triazole moiety were designed and synthesized using the click reaction of azidoalkyloxy-2H-chromen-2-ones with different propargylamines. Propargylamines were obtained by alkylation of various heterocyclic amines with propargyl bromide. Newly synthesized compounds and intermediates were evaluated for their antifungal activity against four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus and Candida albicans). Antibacterial studies were also carried out against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis and Staphylococcus epidermis) and four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Klebsiella pneumoniae). In vitro, bioassay results showed that all the synthesized compounds exhibited excellent activity against fungal strains Aspergillus fumigatus, Aspergillus flavus and Candida albicans. Interestingly, all the compounds have shown even superior activity than the reference drug miconazole against Aspergillus fumigatus. Morpholine and N-acetyl piperazine containing compounds 10c and 10e have shown promising activity against various bacterial strains. Compound 10e was found to be most active against Pseudomonas aeruginosa. Based on, in silico pharmacokinetic studies, compounds 10a-e were identified as lead compounds for future investigation due to their lower toxicity, high drug score values and good oral bioavailability as per OECD guidelines.
- Kushwaha, Khushbu,Kaushik, Nagendra,Lata,Jain, Subhash C.
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supporting information
p. 1795 - 1801
(2014/04/17)
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- Modular synthesis, spectroscopic characterization and in situ functionalization using "click" chemistry of azide terminated amide containing self-assembled monolayers
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A general and modular synthetic route is developed for the synthesis of azidoalkylthiol molecules, which contain an amide functional group, from common and easily available precursors. SAMs (self-assembled monolayers) formed by these amide containing azidoalkylthiols are characterised by attenuated total reflectance FTIR spectroscopy, X-ray photoelectron spectroscopy, contact angle goniometry and surface enhanced Raman spectroscopy. Signature peaks are identified in the data which allows direct observation of all the functional groups on Au electrodes bearing these monolayers. The terminal azide group is functionalised with electroactive ferrocene group in situ, using "click" chemistry. An alkyne bearing heme derivative is covalently attached using the same technique resulting in O2 reducing electrodes.
- Bandyopadhyay, Sabyasachi,Mukherjee, Sohini,Dey, Abhishek
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p. 17174 - 17187
(2013/09/24)
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- Synthesis of a new class of triazole-linked benzoheterocycles via 1,3-dipolar cycloaddition
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A new series of 1,2,3-triazole derivatives have been synthesized from phthalimides and terminal alkynes in the presence of a catalytic amount of CuI. The present protocol affords 1,2,3-triazoles in moderate to good yields (44-89percent).
- Barbosa, Fernanda C. G.,De Oliveira, Ronaldo N.
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p. 592 - 597
(2011/10/30)
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- Synthesis of novel 1,4-disubstituted-1,2,3-triazole semi synthetic analogues of forskolin by click reaction
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New 1,4-disubstituted-1,2,3-triazole analogues of forskolin (5a-g, 6a-g) have been prepared by regioselective propargylation at 1-position followed by Cu(I) catalysed cycloaddition of different alkyl azides under the click reaction conditions. An interesting acyl shift in the base catalysed propargylation afforded a new series of 1,4-disubstituted-1,2,3-triazole analogues of forskolin (6a-g). These analogues have potential selective therapeutic applications as antihypertensive, antiglaucoma, antiasthma and antiobesity agents.
- Koteswara Reddy,Santosh Kumar,Sreenivas,David Krupadanam,Janardhan Reddy
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body text
p. 6537 - 6540
(2012/01/06)
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- 3,6-Bicyclolides
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The present invention discloses compounds of formula (I) or pharmaceutically acceptable salts, esters, or prodrugs thereof: which exhibit antibacterial properties. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject in need of antibiotic treatment. The invention also relates to methods of treating a bacterial infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The invention further includes process by which to make the compounds of the present invention.
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Page/Page column 44
(2008/06/13)
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- HISTONE DEACETYLASE INHIBITORS
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The present invention provides novel HDAC inhibitors and methods of treating diseases using the same.
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Page/Page column 46
(2008/06/13)
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- Alkyl-substituted polyaminohydroxamic acids: A novel class of targeted histone deacetylase inhibitors
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The reversible acetylation of histones is critical for regulation of eukaryotic gene expression. The histone deacetylase inhibitors trichostatin (TSA, 1), MS-275 (2) and suberoylanilide hydroxamic acid (SAHA, 3) arrest growth in transformed cells and in h
- Varghese, Sheeba,Gupta, Deepak,Baran, Tiffany,Jiemjit, Anchalee,Gore, Steven D.,Casero Jr., Robert A.,Woster, Patrick M.
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p. 6350 - 6365
(2007/10/03)
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- α-Methyl polyamines: Metabolically stable spermidine and spermine mimics capable of supporting growth in cells depleted of polyamines
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In order to assess the tolerance of the target enzyme spermine synthase for α-substituents on the aminopropyl moiety of the substrate spermidine, 1- methylspermidine (MeSpd, 2) was synthesized. It was determined that MeSpd is a poor substrate for spermine synthase and is not a substrate for spermidine N1-acetyltransferase, suggesting that α-methylated polyamines might be metabolically stable and therefore useful tools for studying polyamine effects in intact cells. On the basis of initial cellular results with 2, 1- methylspermine (MeSpm, 3) and 1,12-dimethylspermine (Me2Spm, 4) were also synthesized. When added to cells (L1210, SV-3T3, or HT29) depleted of both putrescine and spermidine by prior treatment with α- (difluoromethyl)ornithine (DFMO), these α-methylated polyamines were able to restore cell growth to that observed in the absence of DFMO. In accord with the enzyme data noted above, metabolic studies indicated a slow conversion of 2 to 3, but no metabolism of 4 in these cells. It was concluded from these results that the α-methylated polyamines are able to substitute for the natural polyamines spermidine and spermine in critical biochemical processes which involve polyamines for continued cell growth. In accord with the hypothesis, preliminary data indicate that MeSpd and Me2Spm are as effective as spermidine and spermine, respectively, in promoting the conversion of B- DNA to Z-DNA.
- Lakanen,Coward,Pegg
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p. 724 - 734
(2007/10/02)
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- The Reactivity of Imide Carbnyl Groups in the Intramolecular Aza-Wittig Reaction. An Efficient Route to Iminolactam Derivatives
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Treatment of N-(ω-azidoalkyl)imides with triphenylphosphine in toluene or xylene under reflux gave the corresponding iminolactam derivatives in good yields via Staudinger reaction followed by the intramolecular aza-Wittig reaction.
- Eguchi, Shoji,Takeuchi, Hisato
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p. 602 - 603
(2007/10/02)
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