10125-07-2Relevant academic research and scientific papers
Peptide Decomposition in the Neutral pH Region via the Formation of Diketopiperazines
Steinberg, Spencer M.,Bada, Jeffrey L.
, p. 2295 - 2298 (1983)
In the neutral pH region, the decomposition of the tripeptides Leu-Gly-Gly and Gly-Leu-Gly at 130 deg C and the hexapeptide Phe-Gly-Leu-Gly-Val-Gly at 100 deg C has been found to involve the formation of diketopiperazines from the N-terminal position of the peptides.
En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal-Organic Framework Catalysts
Conic, Dragan,De Azambuja, Francisco,Harvey, Jeremy N.,Loosen, Alexandra,Parac-Vogt, Tatjana N.,Van Den Besselaar, Maxime
, p. 7647 - 7658 (2021)
Peptide bond formation is a challenging, environmentally and economically demanding transformation. Catalysis is key to circumvent current bottlenecks. To date, many homogeneous catalysts able to provide synthetically useful methods have been developed, while heterogeneous catalysts remain largely restricted to the studies addressing the prebiotic formation of peptides. Here, the catalytic activity of Zr6-based metal-organic frameworks (Zr-MOFs) toward peptide bond formation is investigated using dipeptide cyclization as a model reaction. Unlike previous catalysts, Zr-MOFs largely tolerate water, and reactions are carried out under ambient conditions. Notably, the catalyst is recyclable and no additives to activate the COOH group are necessary, which are common limitations of previous methods. In addition, a broad reaction scope tolerates substrates with bulky and Lewis basic groups. The reaction mechanism was assessed by detailed mechanistic and computational studies and features a Lewis acid activation of carboxylate groups by Zr centers toward amine addition in which an alkoxy ligand on adjacent Zr sites assists in lowering the barrier of key proton transfers. The proposed concepts were also used to study the formation of intermolecular peptide bond formation. While intrinsic challenges associated with the catalyst structure and water removal limit a more general intermolecular reaction scope under current conditions, the results suggest that further design of Zr-MOF catalysts could render these materials broadly useful as heterogeneous catalysts for this challenging transformation.
Cyclization-activated prodrugs. Synthesis, reactivity and toxicity of dipeptide esters of paracetamol
Santos, Cledir,Mateus, Maria Luisa,Dos Santos, Ana Paula,Moreira, Rui,De Oliveira, Eliandre,Gomes, Paula
, p. 1595 - 1598 (2005)
Dipeptide esters of paracetamol were prepared in high yields. These compounds are quantitatively hydrolyzed to paracetamol and corresponding 2,5-diketopiperazines at pH 7.4 and 37°C. The reactivity is increased in sarcosine and proline peptides and decreased by bulky side chains at both the N- and C-terminal residues of the dipeptide carrier. Moreover, dipeptide esters of paracetamol did not affect the levels of hepatic glutathione. Thus, dipeptides seem promising candidates as carriers for cyclization-activated prodrugs.
An Optically Active Nucleophile That Catches Its Substrate By Two Points
Janus, Stephan,Sonveaux, Etienne
, p. 3757 - 3760 (1992)
Two diastereomeric cyclic dipeptides are obtained by coupling L or D-His with L-(crowned DOPA).The kinetic data on the reaction of p-nitrophenyl esters of protonated amino-acids and peptides with these His derivatives are reported.
Immobilized Carbodiimide Assisted Flow Combinatorial Protocol to Facilitate Amide Coupling and Lactamization
Aldrich-Wright, Janice R.,Dankers, Christian,Gordon, Christopher P.,Harman, David G.,Nguyen, Thanh V.,Tadros, Joseph
, p. 255 - 267 (2020)
Through a screen of over one hundred and 30 permutations of reaction temperatures, solvents, carbodiimide resins, and carbodiimide molar equivalences, in the presence, absence, or combination of diisopropylamine and benzotriazole additives, a convenient and first reported carbodiimide polymer-assisted flow approach to effect amide coupling and lactamization was developed. The protocol entails injecting a single solution (1:9 dimethylformamide: dichloromethane) containing a carboxylic acid and an amine or linear peptide sequence into a continuous stream of dichloromethane. The protocol remained viable in the absence of base, did not require carboxylate preactivation which, and in concert with minimal workup requirements, enabled the isolation of products in high yields. Compared to the utilization of untethered carbodiimide reagents, the flow procedure was also observed to provide a degree of racemization safety.
Enantioselective Synthesis of Chiral Substituted 2,4-Diketoimidazolidines and 2,5-Diketopiperazines via Asymmetric Hydrogenation
Xiao, Guiying,Xu, Shuang,Xie, Chaochao,Zi, Guofu,Ye, Weiping,Zhou, Zhangtao,Hou, Guohua,Zhang, Zhanbin
, p. 5734 - 5738 (2021/08/01)
An enantioselective hydrogenation of 5-alkylidene-2,4-diketoimidazolidines (hydantoins) and 3-alkylidene-2,5-ketopiperazines catalyzed by the Rh/f-spiroPhos complex under mild conditions has been developed, which provides an efficient approach to the highly enantioselective synthesis of chiral hydantoins and 2,5-ketopiperazine derivatives with high enantioselectivities up to 99.9% ee.
Anti-biofilm and anti-adherence properties of novel cyclic dipeptides against oral pathogens
Simon, Ga?lle,Bérubé, Christopher,Voyer, Normand,Grenier, Daniel
, p. 2323 - 2331 (2018/12/11)
Microorganisms embedded in a biofilm are significantly more resistant to antimicrobial agents and the defences of the human immune system, than their planktonic counterpart. Consequently, compounds that can inhibit biofilm formation are of great interest for novel therapeutics. In this study, a screening approach was used to identify novel cyclic dipeptides that have anti-biofilm activity against oral pathogens. Five new active compounds were identified that prevent biofilm formation by the cariogenic bacterium Streptococcus mutans and the pathogenic fungus Candida albicans. These compounds also inhibit the adherence of microorganisms to a hydroxylapatite surface. Further investigations were conducted on these compounds to establish the structure–activity relationship, and it was deduced that the common cleft pattern is required for these molecules to act effectively against biofilms.
Water-Tolerant and Atom Economical Amide Bond Formation by Metal-Substituted Polyoxometalate Catalysts
De Azambuja, Francisco,Parac-Vogt, Tatjana N.
, p. 10245 - 10252 (2019/11/03)
A simple, safe, and inexpensive amide bond formation directly from nonactivated carboxylic acids and free amines is presented in this work. Readily available Zr(IV)- and Hf(IV)-substituted polyoxometalates (POM) are shown to be catalysts for the amide bond formation reaction under mild conditions, low catalyst loading, and without the use of water scavengers, dry solvents, additives for facilitating the amine attack, or specialized experimental setups commonly employed to remove water. Detailed mechanistic investigations revealed the key role of POM scaffolds which act as inorganic ligands to protect Zr(IV) and Hf(IV) Lewis acidic metals against hydrolysis and preserve their catalytic activity in amide bond formation reactions. The catalysts are compatible with a range of functional groups and heterocycles useful for medicinal, agrochemical, and material chemists. The robustness of the Lewis acid-POM complexes is further supported by the catalyst reuse without loss of activity. This prolific combination of Zr(IV)/Hf(IV) and POMs inaugurates a powerful class of catalysts for the amide bond formation, which overcomes key limitations of previously established Zr(IV)/Hf(IV) salts and boron-based catalysts.
Interfacial supramolecular biomimetic epoxidation catalysed by cyclic dipeptides
Bérubé, Christopher,Barbeau, Xavier,Cardinal, Sébastien,Boudreault, Pierre-Luc,Bouchard, Corinne,Delcey, Nicolas,Lagüe, Patrick,Voyer, Normand
, p. 330 - 349 (2017/03/15)
We synthesised a library of cis- and trans-cyclic dipeptides and evaluated their efficacy as catalysts in the asymmetric Weitz-Scheffer epoxidation of trans-chalcone. A thorough investigation relying on structure-activity studies and computational studies provided insights into the mechanism of the process. Our results revealed some structural features required for efficient conversion and for introduction of chirality into the product. The cyclic dipeptide acts as a catalyst by templating a supramolecular arrangement at the aqueous-organic interface required for efficient transformations to occur. Among all cyclic dipeptides investigated, cyclo(Leu-Leu) was the most efficient supramolecular catalyst.
A general method for the facile synthesis of optically active 2-substituted piperazines via functionalized 2,5-diketopiperazines
Ashton, Kate S.,Denti, Mitchell,Norman, Mark H.,St. Jean Jr., David J.
supporting information, p. 4501 - 4504 (2014/08/05)
Upon utilization of some common methods described in the literature for the synthesis of chiral, 2-substituted 2,5-diketopiperazines, extensive racemization was observed. Further investigation showed that heating in the presence of a mild base racemized the chiral center in the product diketopiperazines. A generalized, readily scalable route was sought and, after investigating the effect of base and temperature, conditions were identified that promoted cyclization without erosion of enantiomeric excess. An array of functionalization was tolerated and this procedure serves as a useful and reliable method for the facile synthesis of this important class of compounds.
