- Kinetics and mechanism of the dehydration reaction of sarcosine to a bislactame through diacyclperoxide intermediate in strong acidic medium
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The influence of substitution on the amine functional group of glycine in the permanganic oxidation of such an α-amino acid in moderately concentrated sulfuric acid medium has been investigated. Reaction products analysis has revealed that contrary to the usual α-amino acid oxidation product, which is an aldehyde species, a valuable compound, namely 1,4-dimethylpiperazine-2,5-dione, has been obtained as the main product via a cheap, simple, efficient, and novel method. Sarcosine has been chosen as a substituted derivative of glycine, and the kinetics and mechanism of its permanganic oxidation have been investigated using a spectrophotometric technique. Conclusive evidence has proven delayed autocatalytic activity for Mn(II) in this reaction, analogous to some α-amino acids. It has been revealed that such activity can show up when a certain concentration ratio of Mn(II) to sarcosine is built up in the medium, which we call the "critical ratio." The magnitude of the latter ratio depends on the sulfuric acid concentration. Considering the "delayed autocatalytic behavior" of Mn(II) ions, rate equations satisfying observations for both catalytic and noncatalytic routes have been presented. The reaction shows first-order dependence on permanganate ions and sarcosine concentrations in both catalytic and noncatalytic pathways, and apparent first-order dependence on Mn 2+ ions in catalytic pathways. The correspondence of pseudo-order rate constants of the catalytic and noncatalytic pathways to Arrhenius and Eyring laws has verified "critical ratio" as well as "delayed autocatalytic behavior" concepts. The activation parameters associated with both pathways have been computed and discussed. Mechanisms for both catalytic and noncatalytic routes involving radical intermediates as well as a product having a diketopiperazine skeleton have been reported for the first time.
- Bahrami, Homayoon,Davari, Mehdi D.,Keshavari, Maryam,Zahedi, Mansour,Bazgir, Ayoob,Moosavi-Movahedi, Ali A.
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- Are α-centered peptide radicals stabilized by a capto-dative effect?
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The kinetics of the thermal C-C-cleavage reaction of the dimer of sarcosine anhydride 5 has been investigated between 295 and 333 °C in mesitylene. From the temperature dependence and from the release of strain on dissociation the cyclic α-peptide radical 6 was calculated to have a radical stabilization enthalpy (RSE) of -6.3 ± 1.3 kcal / mol thus indicating the absence of a synergistic capto-dative effect.
- Brocks, Jochen J.,Welle, Frank M.,Beckhaus, Hans-Dieter,Ruechardt, Christoph
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- RUTHENIUM COMPLEXES AND THEIR USES AS CATALYSTS IN PROCESSES FOR FORMATION AND/OR HYDROGENATION OF ESTERS, AMIDES AND RELATED REACTIONS
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The present invention relates to novel Ruthenium complexes of formulae A1-A4 and their use, inter alia, for (1) dehydrogenative coupling of alcohols to esters; (2) hydrogenation of esters to alcohols (including hydrogenation of cyclic esters (lactones) or cyclic di-esters (di-lactones), or polyesters); (3) preparing amides from alcohols and amines—(including the preparation of polyamides (e.g., polypeptides) by reacting dialcohols and diamines and/or polymerization of amino alcohols and/or forming cyclic dipeptides from p-aminoalcohols; (4) hydrogenation of amides (including cyclic dipeptides, polypeptides and polyamides) to alcohols and amines; (5) hydrogenation of organic carbonates (including polycarbonates) to alcohols or hydrogenation of carbamates (including polycarbamates) or urea derivatives to alcohols and amines; (6) dehydrogenation of secondary alcohols to ketones; (7) amidation of esters (i.e., synthesis of amides from esters and amines); (8) acylation of alcohols using esters; (9) coupling of alcohols with water and a base to form carboxylic acids; and (10) preparation of amino acids or their salts by coupling of amino alcohols with water and a base. The present, invention further relates to the use of certain known Ruthenium complexes for the preparation of amino acids or their salts from amino alcohols.
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Paragraph 0285; 0286
(2017/10/18)
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- EPIDITHIODIKETOPIPERAZINE COMPOUNDS, COMPOSITIONS, AND METHODS
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Epidithiodiketopiperazine compounds, pharmaceutical compositions based thereon and methods of their synthesis, as part of treating, inhibiting and reducing transcription and translation of hypoxia inducible genes are described. In another aspect, the present disclosure describes a method for interfering with hypoxia-induced transcriptional pathway in a cell comprising: contacting the cell with at least one compound disclosed herein. In another aspect, the present disclosure describes a method for treating breast cancer, a solid cancer, a blood cancer, a subject suffering from carcinoma in need of said treatment, and renal cell carcinoma (RCC), comprising: administering to the subject an effective amount of at least one compound disclosed herein. In some embodiments of the methods described herein, the method further comprises administering an additional anti-cancer and/or cytotoxic agent.
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Paragraph 0200
(2015/07/07)
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- Study of intramolecular aminolysis in peptides containing N-alkylamino acids at position 2
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Many peptides and proteins, containing Nα-alkylamino acids (including proline) at the second position, are prone to intramolecular aminolysis (IA) with elimination of N-terminal dipeptide sequence as 2,5-diketopiperazines (DKP). We synthesized a series of short peptides, containing N-alkylamino acids at position 2, and studied their stability in the presence of acetic acid and amines. The presence of side chains in the second and the third amino acid residues and alkylation at Nα of the third amino acid residue slowed down IA. Nα-Alkyl residue in the first amino acid residue impeded IA only in peptides, containing three or more residues. Side chains of the first amino acids did not affect significantly the cleavage rates. Acetic acid promoted IA more strongly than aqueous ammonia, while tertiary amines were less effective. Peptides with methionine-S-oxide residues were more labile than the unoxidized analogs, suggesting intramolecular assistance of the S-oxide group in aminolysis. Surprisingly, intermediate compounds of the formula Boc-Met-MeXaa-Sar-NHR underwent rapid cleavage (endopeptolysis) upon attempted acidolytic deprotection.
- Ryakhovsky, Vladimir V.,Ivanov, Andrey S.
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p. 7070 - 7076
(2012/08/29)
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- Microwave-assisted stereoselective one-pot synthesis of symmetrical and unsymmetrical 2,5-diketopiperazines from unprotected amino acids
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The facile condensation of unprotected amino acids by a phosphite-promoted one-step coupling reaction is a highly efficient synthesis to generate stereoselective and optically pure symmetrical and unsymmetrical functionalized diketopiperazines. The use of microwaves enhanced by small amounts of ionic liquid is accompanied by significant improvement in reaction times and yields. Simple filtration through a pad of silica provides the pure compounds in very good to excellent yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Jainta, Manuel,Nieger, Martin,Braese, Stefan
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experimental part
p. 5418 - 5424
(2009/05/07)
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- The synthetic versatility of alkoxycarbonyl- and hydroxymethyl-piperazine- 2,5-diones
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Alkoxycarbonylpiperazine-2,5-diones are versatile precursors for the α-functionalisation of piperazine-2,5-diones. The alkoxycarbonyl group activates the α-carbon position to alkylation reactions and this provides a mild and selective method for the extension of the carbon framework of piperazine-2,5-diones. In addition, the alkoxycarbonyl group can be converted to the carboxy group, which in turn can be 'deleted' or manipulated for the installation of carbon and/or heteroatom substituents where desired, the latter via N-acyliminium chemistry. We also demonstrate that hydroxymethylpiperazine-2, 5-diones complement carboxypiperazinediones as precursors for the generation of N-acyliminium ions.
- Chai, Christina L.L.,Elix, John A.,Huleatt, Paul B.
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p. 8722 - 8739
(2007/10/03)
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- Multi-purpose functionality for the structural elaboration of the piperazine-2,5-dione motif
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Mild methods for controlled C- and N-alkylation of 3-benzyloxycarbonylpiperazine-2,5-diones are reported. The benzyloxylcarbonyl substituent can also serve as latent functionality for N-acyliminium ion formation and subsequent trapping enables installation of new carbon and/or heteroatom substituents.
- Chai, Christina L. L.,Elix, John A.,Huleatt, Paul B.
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p. 263 - 265
(2007/10/03)
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- Hexafluoroacetone as Protecting Group and Activating Reagent in Amino Acid and Peptide Chemistry, XI. A New Simple Preparative Access to 2,5-Dioxopiperazines and 2,5-Dioxomorpholines
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2,5-Dioxopiperazines with symmetrical as well as unsymmetrical substituent pattern can be obtained via 2,2-bis(trifluoromethyl)-1,3-oxazolidin-5-ones, and 2,5-dioxomorpholines via 2,2-bis(trifluoromethyl)-1,3-dioxolan-4-ones, respectively. Keywords: Hexafluoroacetone; α-Amino acids; α-Hydroxy acids; 2,2-Bis(trifluoromethyl)-1,3-oxazolidin-5-ones; 2,2-Bis(trifluoromethyl)-1,3-dioxolan-4-ones; 2,5-Dioxopiperazines; 2,5-Dioxomorpholines.
- Burger, K.,Rudolph, M.,Windeisen, E.,Worku, A.,Fehn, S.
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p. 453 - 464
(2007/10/02)
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- Divergent, Generalized Synthesis of Unsymmetrically Substituted 2,5-Piperasinediones
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N,N'-Disubstituted 2,5-piperazinediones (12) can be 3,6-dibrominated followed by displacement with sodium 2-mercaptopyridine to furnish syn-1,4-disubstituted 3,6-bis(2'-thiopyridyl)-2,5-piperazinediones (8) in high yield.Precomplexation of these sulfides with silver(I) triflate followed by addition of trimethylsilyl enol ethers leads to chemoselective C-C bond formation, furnishing the homologated piperazinediones 10.The remaining sulfide functionality of 10 is relatively inert to a second substitution.These electrophylic 2,5-piperazinediones provide access to relatively inaccessible, unsymmetrical 2,5-piperazinediones and provide advantages over the corresponding well-known enolate anion approach.Substrates that contain N-p-methoxybenzyl residues can be deprotected to the lipophobic N,N'-unsubstituted 2,5-piperazinediones with aqueous ceric ammonium nitrate.The diastereoselectivity observed in the coupling reactions is discussed in the context of a single crystal X-ray structure determination of 20.
- Williams, Robert M.,Armstrong, Robert W.,Maruyama, Lynn K.,Dung, Jen-Sen,Anderson, Oren P.
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p. 3246 - 3253
(2007/10/02)
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- Synthese d'analogues biheterocycliques du phenanthrene: les methyl-1-benzothieno, benzoselenopyrroles, et methyl-1-benzofuro, benzothieno et benzoselenopyrroles
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The condensation of ethyl sarcosinate on 2- or 3-halogeno 3- or 2-formylbenzofuran, benzothiophene or benzoselenophene, and on the related 2H--3-benzoheterocyclanones is described.In the last instances the resulting compounds were formylated in the 2-position with subsequent cyclodehydration.After hydrolysis and decarboxylation, the 1-methylbenzothieno-, benzoselenopyrroles and the 1-methylbenzofuro, benzothieno- and benzoselenopyrroles were thus obtained.
- Webert, Jean-Marie,Cagniant, Denise,Cagniant, Paul,Kirsch, Gilbert,Weber, Jean-Victor
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