- SylC catalyzes ureido-bond formation during biosynthesis of the proteasome inhibitor syringolin A
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(Chemical Equation Presented) Syringolins are a class of cyclic tripeptide natural products that are potent and irreversible inhibitors of the eukaryotic proteasome. In addition to being hybrid NRPS/PKS molecules, they also feature an unusual ureido-linka
- Imker, Heidi J.,Walsh, Christopher T.,Wuest, William M.
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Read Online
- Heterogeneous H-Bonding in a Foldamer Helix
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Structural characterization of new α/γ-peptide foldamers containing the cyclically constrained γ-amino acid I is described. Crystallographic and 2D NMR analysis shows that γ residue I promotes the formation of a 12/10-helical secondary structure in α/γ-pe
- Fisher, Brian F.,Guo, Li,Dolinar, Brian S.,Guzei, Ilia A.,Gellman, Samuel H.
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- Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts
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A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
- Kervefors, Gabriella,Kersting, Leonard,Olofsson, Berit
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supporting information
p. 5790 - 5795
(2021/03/08)
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- TRANSGLUTAMINASE 2 (TG2) INHIBITORS
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Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit transglutaminase 2 (TG2). Also described herein are methods for using such TG2 inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from TG2 inhibition.
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- Fluorine-containing sulfonyl compound as well as intermediate, preparation method and application thereof
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The invention discloses a fluorine-containing sulfonyl compound as well as an intermediate, a preparation method and application thereof. The fluorine-containing sulfonyl compound disclosed by the invention comprises positive ions and negative ions, wherein the positive ions are shown as the formula I. The fluorine-containing sulfonyl compound can react with substrates to effectively synthetize the fluorine-containing sulfonyl compound; the toxicity is low; the preparation is simple; the use is convenient; the fluorine-containing sulfonyl compound is in a solid stable state at normal temperature. In addition, the substrate applicability of the compound is extremely wide, and a phenol compound and an amine compound can be included; the fluorine-containing sulfonyl compound is a unique solidformation reagent capable of realizing the chemical conversion at present, so that important academic and application values are realized. The formula I is shown in the description.
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Paragraph 0528; 0529; 0530; 0531; 0532
(2018/05/24)
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- Amidation reactions from the direct coupling of metal carboxylate salts with amines
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A general method for the synthesis of amides involving the direct coupling of alkali metal carboxylate salts with amines is described. Amidation of a wide variety of carboxylate salts with either free amines or their ammonium hydrochloride salts can be achieved using HBTU as a coupling agent in combination with Huenig's base. The reaction is highly efficient and is generally complete in as little as 1-2 h, giving the products in good to excellent yields. The protocol is valuable for the coupling of carboxylates for which the corresponding carboxylic acids or acyl chlorides are unstable, less conveniently manipulated/isolated, or are not commercially available. For example, the coupling of amines and α-amino acids with lithium 5-bromo-1H-pyrrole-2-carboxylate, whose corresponding acid that is prone to decarboxylation, allowed for the synthesis of 5-bromo-1H-pyrrole-2-carboxamides, which are analogues of the pyrrole-2-aminoimidazole marine alkaloids. The protocol can be combined with other reactions in a sequenced fashion, as exemplified by the synthesis of acetylenic amides, in a one-pot procedure, via the coupling of a lithium carboxylate salt formed initially by the addition of carbon dioxide to a lithiated terminal alkyne.
- Goodreid, Jordan D.,Duspara, Petar A.,Bosch, Caroline,Batey, Robert A.
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p. 943 - 954
(2014/03/21)
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- In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
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The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
- Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
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supporting information
p. 6824 - 6830
(2013/06/26)
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- A class of novel conjugates of substituted purine and Gly-AA-OBzl: Synthesis and evaluation of orally analgesic activity
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Aimed at the chemotherapy of chronic pain two kinds of analgesic pharmacophores, substituted purine and Gly-AA-OBzl, were coupled via a five-step-reaction procedure and 19 novel conjugates N-[2-chloro-9- (tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters were provided. On mouse-tail flick model their in vivo analgesic activities were assayed. The results indicate that introducing Gly-OC2H 5 into the 6-position of the substituted purine leads to ambiguous increase of the analgesic activity, while introducing Gly-AA-OBzl into this position leads to significant increase of the analgesic activity.
- Kang, Guifeng,Zhao, Ming,Zhang, Xiaoyi,Peng, Li,Li, Chunbo,Mao, Wei,Ye, Weidong,Peng, Shiqi
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supporting information; experimental part
p. 6157 - 6160
(2010/12/19)
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- Esterification of unprotected a-Amino acids in ionic liquids as the reaction media
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Ionic liquid 1,3-dimethylimidazolium methanesulfonate was used to prepare a-amino acids benzylic esters from unprotected amino acids and benzyl chloride. Esterification of several amino acids was achieved with satisfactory yields: by-products can be removed by a simple work-up procedure to afford the pure product. The described method is simple, mild, rapid and save.
- Biondini, Daniele,Brinchi, Lucia,Germani, Raimondo,Goracci, Laura,Savelli, Gianfranco
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experimental part
p. 39 - 44
(2010/08/22)
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- Synthesis and RNase A inhibition study of C2-symmetric bis-isochromenyl sulfones
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A new class of C2-symmetric bis-isochromene derivatives with 3,3′-linkage has been synthesized from bis-propargyl sulfones. The method involves treatment of the sulfones with triethylamine to form the isochromene derivatives presumably via the intramolecular Michael addition to the intermediate bis-allenic sulfones. Interestingly, the product expected from the Garratt-Braverman pathway was not obtained. The bis-isochromene 7d displayed RNase A inhibition activity, much stronger than the isochromene 8 and bis-isocoumarin 9.
- Mitra, Tapobrata,Dutta, Sansa,Basak, Amit
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supporting information; experimental part
p. 2828 - 2831
(2010/07/06)
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- Study on synthesis, characteristics and catalysis properties of novel chiral metal complexes catalysts for 1,3-dipolar cycloaddition reactions of nitrone with electron-rich alkene
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As a new class of potential catalysts for 1,3-dipolar cycloaddition reactions, fourteen L-amino acid Schiff base Cu(II) and Ti(IV) complexes were synthesized, characterized, and evaluated for their catalytic activities in the reaction between C, N-diphenylnitrone and electron-rich ethyl vinyl ether under both homogeneous and in situ conditions. The methods for preparation and utilization of the catalysts were elucidated in detail, and the results of the catalytic reactions were described and discussed as well. Excellent reaction results were found in the presence of some catalysts (20 mol%) with > 90% endo-isoazolidines produced, compared with predominantly exo-isoazolidine produced without a catalyst. In addition, the reaction rate is found to be enhanced remarkably by a Cu(II) complex Schiff base catalyst at room temperature.
- You, Jun,Liu, Bo,Wang, Yi
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experimental part
p. 1010 - 1017
(2010/08/13)
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- Crystal structure analysis and reactivity of N-alkyl- and N-acyldioxathiazinanes
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Cyclic sulfamidates have served as reactive electrophiles for the synthesis of various products, including alkaloids, substituted amines, amino acids and lactams. N-Acyl dioxathiazinanes exhibit enhanced reactivity relative their unsubstituted and N-alkyl
- Galaud, Fabrice,Blankenship, John W.,Lubell, William D.
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experimental part
p. 1121 - 1131
(2009/06/28)
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- Methods and compositions for treating amyloid-related diseases
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Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
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Page/Page column 135
(2010/11/24)
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- Dual-acting agents that possess free radical scavenging and antithrombotic activities: Design, synthesis, and evaluation of phenolic tetrahydro-β-carboline RGD peptide conjugates
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A new approach to construct a single dual-acting agent is described. Compounds 6a-c are potent free radical scavengers as demonstrated by the EC50 values in PC12 cell survival assay in term of NO, H2O2, and {radical dot}OH scavenging activity. The Ach-induced vaso-relaxation assay further confirms the potent NO scavenging activity of compounds 6a-c. In addition, 6a-c are efficacious in a rat arterial thrombosis, and are active in ADP- or PAF-induced in vitro platelet aggregation assay, suggesting that compounds 6a-c also possess anti-thrombotic activities. Since both free radical and thrombogenesis are important risk factors in myocardial ischemic/reperfusion injuries, these dual-acting agents having both free radical scavenging and antithrombolic activities may potentially be beneficial toward their treatment.
- Bi, Wei,Bi, Lanrong,Cai, Jianhui,Liu, Sanguang,Peng, Shiqi,Fischer, Nicholas O.,Tok, Jeffrey B.-H.,Wang, Guohua
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p. 4523 - 4527
(2007/10/03)
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- Fluorous (trimethylsilyl)ethanol: A new reagent for carboxylic acid tagging and protection in peptide synthesis
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Starting with a fluorous analogue of 2-(trimethylsilyl)ethanol, we have designed an easy method for preparing a new fluorous tag (FTMSE) for the protection of carboxylic acids. Because mild conditions are employed in the tag cleavage (TBAF in the presence of 4 A molecular sieves, which prevent racemization), this tag can be advantageously used in the synthesis of peptides and modified peptides, as we have demonstrated with several examples, including the fluorous synthesis of short α- and β-peptides as well as of modified fluorinated retropeptides.
- Fustero, Santos,Sancho, Amador Garcia,Chiva, Gema,Sanz-Cervera, Juan F.,Del Pozo, Carlos,Acena, Jose Luis
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p. 3299 - 3302
(2007/10/03)
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- Synthesis and cytotoxic activities of β-carboline amino acid ester conjugates
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β-Carboline represents a class of compounds with potent anti-tumor activity by intercalating with DNA. To further enhance the cytotoxic potency and bioavailability of β-carboline, a series of novel β-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were tested using a panel of human tumor cell lines. In addition, the membrane permeability of these compounds was evaluated in vitro using a Caco-2 cell monolayer model. The β-carboline amino acid ester conjugates demonstrated improved cytotoxic activity compared to the parental β-carbolines. In particular, the Lys/Arg conjugates were the most potent analogs with an IC50 value of 4 and 1 μM against human cervical carcinoma cells. The low interaction energy of Arg conjugate based on molecular modeling may contribute to its enhanced cytotoxicity. Taken together, this study provided new insights into structure-activity relationships in the β-carboline amino acid ester conjugates and identified the β-carboline Lys/Arg conjugates as promising lead compounds for further in vivo biological and molecular evaluation.
- Zhao, Ming,Bi, Lanrong,Wang, Wei,Wang, Chao,Baudy-Floc'h, Michele,Ju, Jingfang,Peng, Shiqi
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p. 6998 - 7010
(2007/10/03)
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- Capillary electrophoretic separation of enantiomers of amino acids and amino acid derivatives using crown ether and cyclodextrin
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The capillary zone electrophoresis using (+)-18-crown-6-tetracarbonic acid as a chiral selector was a suitable method for the enantiomeric separation of racemates of amino acids and of some amino acid derivatives (esters, dipeptides). The influence of the chemical structure of the compounds on the separation was investigated. After optimization of the separation conditions, baseline separations were obtained for most racemates. The addition of acetonitrile and TBAB yielded an improvement of the separation. Improved selectivity was further observed by the application of a cyclodextrin, HP-β-CD, in combination with the crown ether.
- Salami,Jira,Otto, Hans-Hartwig
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p. 181 - 185
(2007/10/03)
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- PROCESS FOR THE MANUFACTURE OF VALSARTAN
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The present invention relates to a process for the manufacture of Valsartan, an angiotensin receptor blocker (ARB; also called angiotension II receptor antagonist or AT1 receptor antagonist) and salts thereof, to novel intermediates and process steps.
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Page 25-26; 32
(2008/06/13)
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- The (2-phenyl-2-trimethylsilyl)ethoxycarbonyl (Psoc) group - A novel amino protecting group
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A novel silicon containing protecting group has been developed based on the known 2-(trimethylsilyl)ethyl system. The new protecting group is cleaved under very mild conditions by treatment with tetra-n-butylammonium fluoride in CH2Cl2 much more rapidly than the 2-(trimethylsilyl)ethoxycarbonyl group, leading to less side reactions.
- Wagner,Heiner,Kunz
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p. 1753 - 1756
(2007/10/03)
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- Misacylated Transfer RNAs Having a Chemically Removable Protecting Group
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The 4-pentenoyl group and a number of derivatives have been studied as protecting groups for Nα of the aminoacyl moiety in misacylated tRNAs. The unsubstituted 4-pentenoyl group itself was found to function as efficiently as any of the derivatives studied. Four different N-(4-pentenoyl)aminoacyl-tRNACUAS were prepared and shown to undergo deprotection readily upon admixture of aqueous iodine; the derived misacylated tRNAs all functioned well as suppressors of a nonsense codon in an in vitro protein biosynthesizing system. Also prepared were four Nα-(4-pentenoyl)-aspartyl-tRNACUAS that were protected on the side chain carboxylate as the nitroveratryl ester. Following treatment with aqueous iodine, the misacylated suppressor tRNAs incorporated the aspartate derivatives into position 27 of dihydrofolate reductase by suppression of a UAG codon in the mRNA. The suppression yields were significantly better than those obtained when side chain protection was absent. The resulting "caged proteins" were inactive, but full catalytic potential was restored by irradiation under conditions sufficient to effect deprotection of the side chain carboxylate moiety.
- Lodder, Michiel,Golovine, Serguei,Laikhter, Andrei L.,Karginov, Vladimir A.,Hecht, Sidney M.
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p. 794 - 803
(2007/10/03)
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- The synthesis of pure Amadori rearrangement products
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The term "Maillard reaction" is used to describe a complex set of reactions in foods leading to flavour generation and non-enzymatic browning.The first step in this process is the so-called Amadori rearrangement: a reducing saccharide and a peptide fragment react to form an Amadori Rearrangement Product (ARP).To be able to do model studies on flavour generation, gram amounts of pure ARP are required.In the present study, glucose-derived ARPs were synthesised from specifically protected and activated starting compounds.After deprotection and purification, pure ARPs were obtained.This is the first time that ARPs of dipeptides have been isolated.
- Noomen, S. N.,Breel, G. J.,Winkel, C.
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p. 321 - 324
(2007/10/02)
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- Asymmetric Synthesis via Heterocyclic Intermediates, L Trichloroacetimidates, II Asymmetric Synthesis of α-Amino Acid Benzyl Esters via the Bisbenzyl Bislactam Ether of cyclo(-L-Val-Gly-)
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The diketopiperazine cyclo(-L-Val-Gly-) (1) can be O-alkylated under mild acidic reaction conditions with the alkyl trichloroacetimidates 2 to the corresponding bisalkyl bislactim ethers.Alkylation of the bisbenzyl bislactim ether anion of cyclo(-L-Val-Gl
- Groth, Ulrich,Schmeck, Carsten,Schoellkopf, Ulrich
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p. 321 - 324
(2007/10/02)
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