- Silver-Catalyzed Acyl Nitrene Transfer Reactions Involving Dioxazolones: Direct Assembly of N-Acylureas
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Dioxazolones and isocyanides are useful synthetic building blocks, and have attracted significant attention from researchers. However, the silver-catalyzed nitrene transfer reaction of dioxazolones has not been investigated to date. Herein, a silver-catalyzed acyl nitrene transfer reaction involving dioxazolones, isocyanides, and water was realized in the presence of Ag2O to afford a series of N-acylureas in moderate to good yields.
- Yang, Zheng-Lin,Xu, Xin-Liang,Chen, Xue-Rong,Mao, Zhi-Feng,Zhou, Yi-Feng
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supporting information
p. 648 - 652
(2020/12/21)
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- P(III)-Assisted Electrochemical Access to Ureas via in situ Generation of Isocyanates from Hydroxamic Acids
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An external oxidant-free protocol for the generation of isocyanates from hydroxamic acids assisted by trivalent phosphine under mild electrochemical conditions was reported. The process started with the anodic oxidation of hydroxamic acids, followed by reacting with phosphine to form corresponding alkoxyphosphoniums and subsequent rearrangement with the release of tri-substituted phosphine oxide as the driving force to give isocyanates, which were trapped by N-based nucleophiles to produce various ureas. This method provides a broadly applicable procedure to access isocyanate intermediates under mild electrochemical conditions.
- Meng, Haiwen,Sun, Kunhui,Xu, Zhimin,Tian, Lifang,Wang, Yahui
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supporting information
p. 1768 - 1772
(2021/03/26)
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- Alternating Current Electrolysis as Efficient Tool for the Direct Electrochemical Oxidation of Hydroxamic Acids for Acyl Nitroso Diels–Alder Reactions
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The acyl nitroso Diels–Alder reaction of 1,3-dienes with electrochemically oxidised hydroxamic acids is described. By using alternating current electrolysis, their typical electro-induced decomposition could be suppressed in favour of the 1,2-oxazine cycloaddition products. The reaction was optimised using Design of Experiments (DoE) and a sensitivity test was conducted. A mixture of triethylamine/hexafluoroisopropanol served as supporting electrolyte in dichloromethane, thus giving products of high purity after evaporation of the volatiles without further purification. The optimised reaction conditions were applied to various 1,3-dienes and hydroxamic acids, giving up to 96 % isolated yield.
- F?hrmann, Jan,Hilt, Gerhard
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supporting information
p. 20313 - 20317
(2021/08/12)
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- Synthesis of sulfimides and N-Allyl-N-(thio)amides by Ru(II)catalyzed nitrene transfer reactions of N-acyloxyamides
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The N-acyloxyamides were employed as effective N-acyl nitrene precursors in reactions with thioethers under the catalysis of a commercially available Ru(II) complex, from which a variety of sulfimides were synthesized efficiently and mildly. If an allyl group is contained in the thioether precursor, the [2,3]-sigmatropic rearrangement of the sulfimide occurs simultaneously and the N-allyl-N-(thio)amides were obtained as the final products. Preliminary mechanistic studies indicated that the Ru-nitrenoid species should be a key intermediate in the transformation.
- Zhang, Xinyu,Lin, Bo,Chen, Jianhui,Chen, Jiajia,Luo, Yanshu,Xia, Yuanzhi
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supporting information
p. 819 - 825
(2021/02/01)
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- Palladium-catalyzed cascade decarboxylative amination/6- endo-dig benzannulation of o-alkynylarylketones with n-hydroxyamides to access diverse 1-naphthylamine derivatives
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An efficient and practical one-pot strategy to produce highly substituted 1-naphthylamines via sequential palladium-catalyzed decarboxylative amination/intramolecular 6-endo-dig benzannulation reactions has been described. In this reaction, a broad range of electron-rich, electron-neutral, and electron-deficient o-alkynylarylketones react well with N-hydroxyl aryl/alkylamides to give a diversity of 1-naphthylamines in good to excellent yields under mild reaction conditions. The gram-scale synthesis, with benefits such as undiminished product yield and easy transformation, illustrated the practicality of this method.
- Zuo, Youpeng,He, Xinwei,Tang, Qiang,Hu, Wangcheng,Zhou, Tongtong,Shang, Yongjia
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supporting information
p. 3890 - 3894
(2020/05/18)
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- Photocatalytic Intramolecular C-H Amination Using N-Oxyureas as Nitrene Precursors
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Nitrenes are remarkable high-energy chemical species that enable direct C-N bond formation, typically via controlled reactions of metal-stabilized nitrenes. Here, in contrast, the combined use of photocatalysis with careful engineering of the precursor enabled C-H amination forming imidazolidinones and related nitrogen heterocycles from readily accessible hydroxylamine precursors. Preliminary mechanistic results are consistent with the formation of free carbamoyl triplet nitrenes as reactive intermediates.
- Ivanovich, Ryan A.,Polat, Dilan E.,Beauchemin, André M.
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supporting information
p. 6360 - 6364
(2020/09/02)
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- Efficient Copper-Catalyzed Multicomponent Synthesis of N-Acyl Amidines via Acyl Nitrenes
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Direct synthetic routes to amidines are desired, as they are widely present in many biologically active compounds and organometallic complexes. N-Acyl amidines in particular can be used as a starting material for the synthesis of heterocycles and have several other applications. Here, we describe a fast and practical copper-catalyzed three-component reaction of aryl acetylenes, amines, and easily accessible 1,4,2-dioxazol-5-ones to N-acyl amidines, generating CO2 as the only byproduct. Transformation of the dioxazolones on the Cu catalyst generates acyl nitrenes that rapidly insert into the copper acetylide Cu-C bond rather than undergoing an undesired Curtius rearrangement. For nonaromatic dioxazolones, [Cu(OAc)(Xantphos)] is a superior catalyst for this transformation, leading to full substrate conversion within 10 min. For the direct synthesis of N-benzoyl amidine derivatives from aromatic dioxazolones, [Cu(OAc)(Xantphos)] proved to be inactive, but moderate to good yields were obtained when using simple copper(I) iodide (CuI) as the catalyst. Mechanistic studies revealed the aerobic instability of one of the intermediates at low catalyst loadings, but the reaction could still be performed in air for most substrates when using catalyst loadings of 5 mol %. The herein reported procedure not only provides a new, practical, and direct route to N-acyl amidines but also represents a new type of C-N bond formation.
- Van Vliet, Kaj M.,Polak, Lara H.,Siegler, Maxime A.,Van Der Vlugt, Jarl Ivar,Guerra, Célia Fonseca,De Bruin, Bas
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supporting information
p. 15240 - 15249
(2019/10/19)
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- S-glycosyltransferase UGT74B1 can glycosylate both S- and O-acceptors: mechanistic insights through substrate specificity
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UGT74B1 from Arabidopsis thaliana is one of the few characterized glycosyltransferases able to generate a thioglycosidic linkage in vivo, using the sulfur atom of thiohydroximate as the nucleophile in the glycosylation reaction. This critical biosynthetic
- Lafite,Marroun,Coadou,Montaut,Marquès,Schuler,Rollin,Tatibou?t,Daniellou,Oulyadi
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- Consecutive Lossen rearrangement/transamidation reaction of hydroxamic acids under catalyst- and additive-free conditions
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The Lossen rearrangement is a classic process for transforming activated hydroxamic acids into isocyanate under basic or thermal conditions. In the current report we disclosed a consecutive Lossen rearrangement/transamidation reaction in which unactivated hydroxamic acids were converted into N-substituted formamides in a one-pot manner under catalyst- and additive-free conditions. One feature of this novel transformation is that the formamide plays triple roles in the reaction by acting as a readily available solvent, a promoter for additive-free Lossen rearrangement, and a source of the formyl group in the final products. Acyl groups other than formyl could also be introduced into the product when changing the solvent to other low molecular weight aliphatic amide derivatives. The solvent-promoted Lossen rearrangement was better understood by DFT calculations, and the intermediacy of isocyanate and amine was supported well by experiments, in which the desired products were obtained in excellent yields under similar conditions. Not only monosubstituted formamides were synthesized from hydroxamic acids, but also N,N-disubstituted formamides were obtained when secondary amines were used as precursors.
- Jia, Mengmeng,Zhang, Heng,Lin, Yongjia,Chen, Dimei,Chen, Yanmei,Xia, Yuanzhi
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p. 3615 - 3624
(2018/05/26)
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- Experimental and computational studies on H2O-promoted, Rh-catalyzed transient-ligand-free ortho-C(sp2)-H amidation of benzaldehydes with dioxazolones
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An efficient and convenient ligand-free, rhodium-catalyzed ortho-C(sp2)-H amidation of benzaldehydes with dioxazolones using H2O as the key promoter is described. Using this protocol, a wide range of benzaldehyde substrates were selectively amidated in good to excellent yields with broad functional group compatibility. KIE experiments revealed that the C-H bond activation was likely the rate-limiting step. In addition, computational studies indicated that the catalyst precursor interacted with water and dioxazolones to generate the active catalytic species. Notably, the practicality and efficacy of this method were illustrated by a late-stage amidation of an estrone-derived molecule and further transformations of the amidated product.
- Ding, Jun,Jiang, Wei,Bai, He-Yuan,Ding, Tong-Mei,Gao, Dafang,Bao, Xiaoguang,Zhang, Shu-Yu
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supporting information
p. 8889 - 8892
(2018/08/17)
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- Synthesis, characterization and DNA nuclease activity of oxo-peroxomolybdenum(VI) complexes
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The synthesis and structural characterization of two oxo-peroxo molybdenum(VI) complexes, [Mo(O)(O)2(PAA)]? (1) and [Mo(O)(O)2(PAH)]? (2), with phenylacetic acid (PAA) and 2-phenylacetylhydroxamic acid (PAHH) li
- Paul, Shiv Shankar,Selim, Md.,Mukherjea, Kalyan K.
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p. 1739 - 1760
(2017/05/15)
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- Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
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Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
- Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
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p. 9067 - 9089
(2017/11/14)
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- Synthesis and biological activity of salinomycin-hydroxamic acid conjugates
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Several salinomycin-hydroxamic acid conjugates were designed and synthesized. Most conjugates showed better antiproliferative activities than salinomycin in HT-29 colon cancer, HGC-27 gastric cancer, and especially in MDA-MB-231 triple-negative human breast cancer cells. These conjugates are stable in cell culture media, and they showed much better biological activities than the 1:1 physical mixture with hydroxamic acids and salinomycin. The better membrane permeability and hydrolysis rate of the conjugates may lead to the activity improvements.
- Li, Bo,Wu, Jun,Zhang, Wenxuan,Li, Zhongwen,Chen, Gang,Zhou, Qi,Wu, Song
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p. 1624 - 1626
(2017/03/16)
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- A base-mediated self-propagative Lossen rearrangement of hydroxamic acids for the efficient and facile synthesis of aromatic and aliphatic primary amines
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A variety of aromatic and aliphatic hydroxamic acids were converted to the corresponding primary amines via base-mediated rearrangement. This rearrangement could proceed with less than 1 equiv. of K2CO3 in polar solvents under thermal conditions with no external reagents. This rearrangement has several features including no external activating agents needed for promoting the rearrangement, less than one equivalent of a base is sufficient for the reaction, and a clean reaction in which only carbon dioxide is produced as a by-product. A self-propagating mechanism via an isocyanate intermediate is proposed and elementary reaction steps, namely, chain propagation reactions are supported by experiments.
- Ohtsuka, Naoya,Okuno, Moriaki,Hoshino, Yujiro,Honda, Kiyoshi
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supporting information
p. 9046 - 9054
(2016/10/05)
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- Curtius-like Rearrangement of an Iron-Nitrenoid Complex and Application in Biomimetic Synthesis of Bisindolylmethanes
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A Curtius-like rearrangement of hydroxamates to isocyanates was discovered. This reaction was initiated from an iron(II)-nitrenoid complex, which was generated by the iron(II)-catalyzed cleavage of N-O bonds of functionalized hydroxamates. To demonstrate the efficiency of this new Curtius-like rearrangement in synthetic chemistry, a biomimetic strategy for the one-pot preparation of bisindolylmethanes was developed.
- Li, Dashan,Wu, Ting,Liang, Kangjiang,Xia, Chengfeng
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supporting information
p. 2228 - 2231
(2016/06/01)
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- An Experimental and Computational Approach to Understanding the Reactions of Acyl Nitroso Compounds in [4 + 2] Cycloadditions
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Catalytic aerobic oxidation of phenyl hydroxycarbamate 1 and 1-hydroxy-3-phenylurea 2 using CuCl2 and 2-ethyl-2-oxazoline in methanol gave acyl nitroso species in situ, which were trapped in nitroso-Diels-Alder (NDA) reactions with various dienes to afford the corresponding cycloadducts in high yields (90-98%). Competing ene products were also present for dienes containing both alkene π-bonds and allylic σ-bonds, and the ene yields are higher with 1 than with 2. The use of the chiral hydroxamic acid, (R)-1-hydroxy-3-(1-phenylethylurea) 3 (same conditions) gave NDA cycloadducts in high yields (97-99%) with no ene product from 2,3-dimethyl-1,3-butadiene. NDA cycloadducts were not obtained from other hydroxamic acid analogues [RCONHOH (R = PhCH2 4; Ph(CH2)2 5; Ph(CH2)3 6; Ph(CH2)4 7; Ph 8; 2-pyridyl 9; 3-pyridyl 10] with various dienes using copper-oxidation but rather were obtained using sodium periodate, resulting in variable NDA yields (13-51%) from hydroxamic acids 1-10 with cyclohexa-1,3-diene and 2,3-dimethyl-1,3-butadiene (several cycloadducts characterized by X-ray crystallography). The NDA and nitroso-ene reaction pathways of nitroso intermediates with dienes were mapped by DFT computations (B3LYP/6-31G), which showed that the acyl nitroso species are super-reactive and that activation energies in the NDA processes are lower than the isomerization barriers between some cis- and trans-butadienes.
- Chaiyaveij, Duangduan,Batsanov, Andrei S.,Fox, Mark A.,Marder, Todd B.,Whiting, Andrew
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p. 9518 - 9534
(2015/10/12)
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- One-pot synthesis of hydroxamic acids from aldehydes and hydroxylamine
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A one-pot oxidative transformation of aldehydes into hydroxamic acids by the use of an aqueous solution of hydroxylamine is reported. The methodology gives high yields and makes use of cheap, abundant and easily available reagents.
- Dettori, Giovanna,Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 2709 - 2713
(2014/09/17)
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- Synthesis and structural characterization of dioxomolybdenum and dioxotungsten hydroxamato complexes and their function in the protection of radiation induced DNA damage
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The synthesis and structural characterization of two novel dioxomolybdenum(vi) (1) and dioxotungsten(vi) (2) complexes with 2-phenylacetylhydroxamic acid (PAHH) [M(O)2(PAH)2] [M = Mo, W] have been accomplished. The dioxomolybdenum(vi
- Paul, Shiv Shankar,Selim, Md.,Saha, Abhijit,Mukherjea, Kalyan K.
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p. 2835 - 2848
(2014/02/14)
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- Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate-mediated lossen rearrangement: Single-pot racemization-free synthesis of hydroxamic acids and ureas from carboxylic acids
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Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate (4-NBsOXY) mediated Lossen rearrangement and its application for the synthesis of ureas is demonstrated. Required hydroxamic acids for the Lossen rearrangements were synthesized from carboxylic acids using the same reagent. Finally, reaction of an amine with the produced isocyanate resulted in urea. Good yields without racemization were achieved under milder and simpler reaction conditions. Reactions are compatible with common N-protecting groups, such as Boc, Fmoc, Cbz, and benzyl, as well as various OH protecting groups, such as tBu and Bzl. Conversion from carboxylic acid to urea is achieved in one pot. Most importantly, byproducts Oxyma [ethyl 2-cyano-2-(hydroxyimino)acetate] and 4-nitrobenzenesulfonic acid can be recovered easily and can be recycled to prepare the reagent. Thus, the method is environmentally friendly and cost-effective.
- Thalluri, Kishore,Manne, Srinivasa Rao,Dev, Dharm,Mandal, Bhubaneswar
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p. 3765 - 3775
(2014/05/20)
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- Introducing catalytic lossen rearrangements: Sustainable access to carbamates and amines
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A new, highly efficient and environmentally benign catalytic variant of the Lossen rearrangement is described. Dimethyl carbonate (DMC) as green activation reagent of hydroxamic acids in presence of catalytic amounts of tertiary amine bases {1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 1,8-biazabicyclo 5.4.0 undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), and triethylamine} and small quantities of methanol initiate the rearrangement. Methyl carbamates were obtained in good to moderate yields when aliphatic hydroxamic acids were employed in this catalytic Lossen rearrangement; under the same conditions aromatic hydroxamic acids yielded anilines. Notably, the mixture of DMC/methanol was recycled several times without observing decreased yields, thus minimizing the produced waste. Moreover, several other organic carbonates were successfully employed in the introduced catalytic Lossen rearrangement procedure. Copyright
- Kreye, Oliver,Wald, Sarah,Meier, Michael A. R.
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supporting information
p. 81 - 86
(2013/03/13)
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- Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif
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Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound 14 (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif. The binding of these highly efficient ligands for HDAC6 is rationalized via structure-activity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.
- Wagner, Florence F.,Olson, David E.,Gale, Jennifer P.,Kaya, Taner,We?wer, Michel,Aidoud, Nadia,Thomas, Méryl,Davoine, Emeline L.,Lemercier, Bérénice C.,Zhang, Yan-Ling,Holson, Edward B.
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supporting information
p. 1772 - 1776
(2013/04/10)
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- N-methylimidazole-catalyzed synthesis of carbamates from hydroxamic acids via the lossen rearrangement
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An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.
- Yoganathan, Sabesan,Miller, Scott J.
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supporting information
p. 602 - 605
(2013/04/11)
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- Synthesis, structural characterization and catalytic activity of a multifunctional enzyme mimetic oxoperoxovanadium(v) complex
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The synthesis and structural characterization of a novel oxoperoxovanadium(v) complex [VO(O2)(PAH)(phen)] containing the ligands 2-phenylacetohydroxamic acid (PAHH) and 1,10-phenanthroline (phen) has been accomplished. The oxoperoxovanadium(v) complex was found to mimic both vanadate-dependent haloperoxidase (VHPO) activity as well as nuclease activity through effective interaction with DNA. The complex is the first example of a structurally characterized stable oxoperoxovanadium(v) complex with a coordinated bi-dentate hydroximate moiety (-CONHO-) from 2-phenylacetohydroximate (PAH). The oxoperoxovanadium(v) complex has been used as catalyst for the peroxidative bromination reaction of some unsaturated alcohols (e.g. 4-pentene-1-ol, 1-octene-3-ol and 9-decene-1-ol) in the presence of H2O2 and KBr. The catalytic products have been characterized by GC-MS analysis and spectrophotometric methods. The DNA binding of this complex has been established with CT DNA whereas the DNA cleavage was demonstrated with plasmid DNA. The interactions of the complex with DNA have been monitored by electronic absorption and fluorescence emission spectroscopy. Viscometric measurements suggest that the compound is a DNA intercalator. The nuclease activity of this complex was confirmed by gel electrophoresis studies.
- Si, Tapan K.,Paul, Shiv S.,Drew, Michael G. B.,Mukherjea, Kalyan K.
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experimental part
p. 5805 - 5815
(2012/06/15)
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- Copper-catalyzed cross-coupling of O -alkyl hydroxamates with aryl iodides
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N-Aryl-O-alkylhydroxamic acid derivatives were prepared by copper-catalyzed cross-coupling of hydroxamates with aryl iodides. The reaction conditions are compatible with standard hydroxy-protecting groups on the hydroxylamine moiety and are applicable to
- Kukosha, Tatyana,Trufilkina, Nadezhda,Belyakov, Sergey,Katkevics, Martins
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supporting information; experimental part
p. 2413 - 2423
(2012/09/07)
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- Glucosinolate synthesis: A hydroxamic acid approach
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A new method for accessing the thiohydroximate function allows an alternative synthetic pathway to glucosinolates. O-Silylated hydroxamic acids were prepared and were then activated with triflic anhydride to generate transient nitrile oxides to be condens
- Cerniauskaite, Deimante,Rousseau, Jolanta,Sackus, Algirdas,Rollin, Patrick,Tatibouet, Arnaud
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experimental part
p. 2293 - 2300
(2011/06/16)
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- NOVEL DXR INHIBITORS FOR ANTIMICROBIAL THERAPY
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The present invention generally concerns particular methods and compositions for antimicrobial therapy. In particuarl embodiments, the compositions target DXR. In specific embodiments, the compositions are electron-deficient heterocyclic rings.
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Page/Page column 69; 75
(2011/05/05)
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- 1-propanephosphonic acid cyclic anhydride (T3P) as an efficient promoter for the Lossen rearrangement: Application to the synthesis of urea and carbamate derivatives
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The synthesis of hydroxamic acids starting from carboxylic acids employing 1-propanephosphonic acid cyclic anhydride (T3P) activation is described. Application of ultrasonication accelerates this conversion. Further, the T3P has also been employed to activate the hydroxamates, leading to isocyanates via the Lossen rearrangement. The isocyanates were trapped with suitable nucleophiles to afford the corresponding ureas and carbamates. Georg Thieme Verlag Stuttgart New York.
- Vasantha, Basavalingappa,Hemantha, Hosahalli P.,Sureshbabu, Vommina V.
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experimental part
p. 2990 - 2996
(2010/10/21)
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- Microwave-assisted conversion of 4-nitrophenyl esters into 0-protected hydroxamic acids
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The microwave-assisted synthesis of O-protected hydroxamic acids starting from 4-nitrophenyl esters and O-protected hydroxylamines is described. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009.
- Kurz, Thomas,Pein, Miriam K.,Marek, Linda,Behrendt, Christoph T.,Spanier, Lukas,Kuna, Krystina,Bruecher, Karin
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experimental part
p. 2939 - 2942
(2009/10/11)
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- Syntheses and biological activity studies of novel sterol analogs from nitroso diels-alder reactions of ergosterol
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A serles of novel sterol analogs was prepared using nitroso Dlels-Alder reactions with ergosterol. Most cycloaddltlon reactions proceeded In an excellent reglo- and stereoselective fashion. Further N-O bond cleavage of cycloadducts generated compounds with biological activity In PC-3 and MCF-7 cancer cell lines
- Yang, Baiyuan,Miller, Patricia A.,Moellmann, Ute,Miller, Marvin J.
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body text
p. 2828 - 2831
(2009/12/06)
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- Hydroxamates: Relationships between structure and plasma stability
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Hydroxamates are valuable tools for chemical biology as well as interesting leads for medicinal chemistry. Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure-plasma stability for hydroxamates. We define some structural rules to predict or improve the plasma stability in the preclinical stage.
- Flipo, Marion,Charton, Julie,Hocine, Akila,Dassonneville, Sandrine,Deprez, Benoit,Deprez-Poulain, Rebecca
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experimental part
p. 6790 - 6802
(2010/04/04)
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- Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase
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1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-negative bacteria. A coordination chemistry and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 μM. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL).
- Deng, Lisheng,Sundriyal, Sandeep,Rubio, Valentina,Shi, Zheng-Zheng,Song, Yongcheng
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supporting information; experimental part
p. 6539 - 6542
(2010/04/04)
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- Efficient continuous flow synthesis of hydroxamic acids and suberoylanilide hydroxamic acid preparation
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A continuous flow tubing reactor can be used to readily transform methyl or ethyl carboxylic esters into the corresponding hydroxamic acids. Flow rate, reactor volume, and temperature were optimized for the preparation of a small collection of hydroxamic acids. Synthetic advantages were identified as an increased reaction rate and higher product purity. This method was also successfully applied to the multistep preparation of suberoylanilide hydroxamic acid, a potent HDAC inhibitor used in anticancer therapy.
- Riva, Elena,Gagliardi, Stefania,Mazzoni, Caterina,Passarella, Daniele,Rencurosi, Anna,Vigo, Daniele,Martinelli, Marisa
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supporting information; experimental part
p. 3540 - 3543
(2009/09/30)
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- Convenient synthesis of a library of discrete hydroxamic acids using the hydroxythiophenol (Marshall) resin
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Several resins have reportedly been used to synthesize hydroxamic acids except for the hydroxythiophenol (Marshall) resin. Herein, we report the use of the Marshall resin to synthesize hydroxamic acids from carboxylic acids and its application to convert a library of 14 discrete aliphatic and aromatic carboxylic acids including N-protected amino acids to their corresponding hydroxamic acids in good yields.
- Choi, Jinil,Park, Jewn Giew,Pang, Yuan-Ping
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p. 1103 - 1106
(2008/09/17)
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- Microwave-assisted transformation of esters into hydroxamic acids
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A general, mild and efficient procedure with which to access hydroxamic acids, in good yields and purity, is reported. Esters are used as substrates and reacted with hydroxylamine, in the presence of a base, under microwave activation. The method has been
- Massaro, Assunta,Mordini, Alessandro,Reginato, Gianna,Russo, Francesco,Taddei, Maurizio
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p. 3201 - 3204
(2008/09/16)
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- Preparation of hydroxamic acids from esters in solution and on the solid phase
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The present invention provides a novel method for the formation of hydroxamic acids comprising reacting under suitable conditions an ester with hydroxylamine in the presence of cyanide anion.
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Page/Page column 2-4
(2010/02/15)
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- Angeli-Rimini's reaction on solid support: A new approach to hydroxamic acids
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Angeli-Rimini's reaction has been performed for the first time on solid phase. A convenient one-step procedure for the synthesis of hydroxamic acids starting from aldehydes and solid-supported N-hydroxybenzenesulfonamide is reported. The hydroxamates are isolated in good to high yields and purities by simple evaporation of the volatile solvents, after treatment of the crude reaction mixture with sequestering agents.
- Porcheddu, Andrea,Giacomelli, Giampaolo
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p. 7057 - 7059
(2007/10/03)
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- Improved solution- and solid-phase preparation of hydroxamic acids from esters
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The addition of small amounts of solid KCN to solution and solid-phase esters in THF/MeOH/50% aqueous NH2OH increases the efficiency of their transformation to the corresponding hydroxamic acids.
- Ho, Chih Y.,Strobel, Eric,Ralbovsky, Janet,Galemmo Jr., Robert A.
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p. 4873 - 4875
(2007/10/03)
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- Protective solutions for organs
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Described is a protective solution for avoiding ischemic, storage or ischemia/reperfusion to organs, or to isolated cell systems, or to tissue components after perfusion, surgery, transplantation, or cryopreservation and subsequent reperfusion, which contains alkali ions, and if need be also alkaline earth ions as the electrolyte, a buffer e.g. on a histidine derivation basis, as well as a polyol and/or a saccharide, has an osmolarity of about 290 mosm/l to about 350 mosm/l, as well as a pH value of about 6.8 to about 7.4, and to which hydroxamic acid, and/or one or more hydroxamic acid derivatives are added.
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- Simple one-flask method for the preparation of hydroxamic acids
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(Matrix presented) A one-step conversion of carboxylic acids to hydroxamic acids under very mild conditions is described. This simple and efficient method has been applied for the synthesis of enantiopure hydroxamate of α-amino acids and peptides.
- Giacomelli, Giampaolo,Porcheddu, Andrea,Salaris, Margherita
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p. 2715 - 2717
(2007/10/03)
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- A convenient parallel synthesis of low molecular weight hydroxamic acids using polymer-supported 1-hydroxybenzotriazole
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A convenient two-step procedure for the parallel synthesis of hydroxamic acids from carboxylic acids and hydroxylamine in good to high yields is reported. It involves the formation of a polymer-bound HOBt active ester and subsequent reaction with O-protected or free hydroxylamine. The hydroxamates are isolated with high purities by simple evaporation of volatile solvents. The use of free hydroxylamine leads to increased yields while maintaining high purities. Recycling of the spent resin to produce the same or a different hydroxamic acid has been achieved by a three-step protocol which is easily amenable to automation and cost-economical. The method presented here is well suited to the preparation of the title compounds and can be used effectively to synthesise large molecules containing a hydroxamic acid group.
- Devocelle, Marc,McLoughlin, Brian M.,Sharkey, Caroline T.,Fitzgerald, Desmond J.,Nolan, Kevin B.
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p. 850 - 853
(2007/10/03)
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- Synthesis and Reactions of α-Bromo-N-alkoxyimidates
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The reaction of alkyl hydroxamates 2 with (C2H5)3O*BF4 in CH2Cl2 affords N-alkoxyimidates 3.The direct alkylation of hydroxamic acids 1 with 1,2-dibromoethane gives the 5,6-dihydro-1,4,2-dioxazine derivatives 4.The reactions of the acyclic imidates 3 as well as the cyclic N-alkoxyimidates 4 with N-bromosuccinimide in CCl4 produces the α-bromoimidates 5a-d and 6a-d.The α-bromine atom in the bromides 5b, d and 6a, b, d can be displaced by fluorine and azido substituents to yield the α-fluoro-N-alkoxyimidates 7b, d and 10a, b, d and the α-azido compounds 8b, d and 11a, b, d, respectively.The reduction of the azides 8b, d and 11a, b, d affords the α-aminoimidates 9b, d and 12a, b, d, respectively.The reaction of the bromides 6a-d with benzene derivatives 14a-d in the presence of AgBF4 affords the aromatic substitution products 15a-d.Acid-catalyzed hydrolysis of 15a, c gives the arylsubstituted carboxylic acids 16 and 17. Key Words: Imidates, α-bromo- / 1,4,2-Dioxazines
- Shatzmiller, Shimon,Bercovici, Sorin
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p. 997 - 1004
(2007/10/02)
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- Syntheses of Diamino-dideoxylyxose Derivatives using Acylnitroso Dienophiles
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N-Acylnitroso derivatives 6 which were prepared by in-situ oxidation of the corresponding hydroxamic acids 5 reacted instantaneously and in high yields with dihydropyridine 4.The Diels-Alder adducts 8 were formed regiospecifically with the acylnitroso dienophiles 6a-c, whereas the dienophiles 6d-f gave mixtures of both regioisomers 7 and 8.These and some other results were best explained by the FMO theory.The Diels-Alder adducts 7 and 8 gave the corresponding 'anti'-cis-glycols when reacted with OsO4/N-methylmorpholine N-oxide.Hydrogenolysis of the N-O bond folloved by peracetylation led to the expected aminolyxose derivatives 14 and 16.A similar sequence, using 4 and the hydroxamic-acid derivative 18 of (+)-D-mandelic acid led, with a poor assymmetric induction, to a mixture of the expected optically active aminolyxose compounds 19A/19B.
- Defoin, Albert,Fritz, Hans,Schmidlin, Christian,Streith, Jacques
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p. 554 - 569
(2007/10/02)
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- ON THE RATE MAXIMA OBSERVED IN THE ACID-HYDROLYSIS OF SOME ALKYLHYDROXAMIC ACIDS
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Rate maxima seen in the acid-hydrolysis of 2,2-dimethyl- and phenylacetohydroxamic acids ere discussed in terms of acid-base equilibria, transition state formation and the different acidity functions that control these steps.
- Buglass, A. J.,Dorr, M.,Juffkins, M.
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p. 3283 - 3284
(2007/10/02)
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- Direct Conversion of Hydroxamic Acids into Nitriles
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Aromatic and aliphatic nitriles are prepared in excellent yield from the corresponding hydroxamic acids and phosphorus tribromide in benzene solution.
- Liguori, Angelo,Sindona, Giovanni,Romeo, Giovanni,Uccella, Nicola
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- Spectrophotometric Study of 2-Phenylacetohydroxamic Acid Chelates of Cu(II) and Dioxouranium(VI)
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Stability constants of 2-phenylacetohydroxamic acid (PAHA) chelates of Cu(II) and UO2(2+) have been determined spectrophotometrically at 30 deg C and 0.10 ionic strength adopting the extrapolation methods of Yatsimirskii and Leden.High stability of these
- Damoder Reddy,Sethuram, B.,Navaneeth Rao, T.
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p. 495 - 499
(2007/10/02)
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