36357-32-1Relevant articles and documents
Mechanism of 2,5-dioxopiperazine formation
Capasso, Sante,Vergara, Alessandro,Mazzarella, Lelio
, p. 1990 - 1995 (1998)
The cyclization of H-Ala-Pro-NH2 to the 2,5-dioxopiperazine (DKP) has been Studied as a model for the spontaneous cleavage of the peptide bond with concomitant formation of 2,5-dioxopiperazine that can occur at the N-terminus of a polypeptide chain. The reaction involves pre-equilibrium attack of the N-terminal amino group on the carbonyl carbon of the second residue giving a zwitterionic intermediate, T(±) which is in acid-base equilibrium with various forms characterized by the different grades of protonation, T0, T+ and T-. The Bronsted plot for the base-catalysis and the pH-rate profile give pK(a) ~ 7 and ~ 13 for the equilibria T- + H+ ? T(±) + T(-) + H(+) ? T0 respectively. The reaction is subjects to general base and general acid cataysis on different steps. Departure of the amino group from T0 and T- by two parallel routes gives the product. The bifunctional acid catalyst HCO3- strongly increase the reaction rate and at high concentrations cause a of the rate-limiting step. At high pH, the overall reaction rate is limited by the trans - cis isomerization of the Ala-Pro peptide bond.
Solvent effects on diketopiperazine formation from N-terminal peptide residues
Capasso, Sante,Mazzarella, Lelio
, p. 329 - 332 (1999)
The kinetics of diketopiperazine formation from the peptide H-Ala-Pro-NH2 with the unprotected amino group in the form of its trifluoroacetate salt have been investigated in a large number of solvents, including aprotic and hydroxylic solvents. The first-order rate constant is considerably affected by the solvent properties, its value spanning more than three orders of magnitude. Moreover, alkylammonium carboxylate salts are efficient catalysts of the reaction. The correlation with Kamlet-Taft solvent parameters shows that the reaction rate is retarded by solvents with a high capacity to stabilise solutes that are charged or dipolar, and that are hydrogen donors and/or acceptors. Solvents with high cohesive energy density values significantly increase the reaction rate. These results are discussed in terms of a proton switch in the rate determining step and of solvation stabilisation of the initial state of the peptide and of the transition state of the rate-limiting step.
Cyclo(l-proline-l-serine) Dipeptide Suppresses Seed Borne Fungal Pathogens of Rice: Altered Cellular Membrane Integrity of Fungal Hyphae and Seed Quality Benefits
Poonia, Baninderjit Kaur,Sidhu, Anjali,Sharma, Anju Bala
, p. 2160 - 2168 (2022/02/23)
Five proline-containing diketopiperazines (Pro-DKPs) produced by antagonistic microorganisms as secondary metabolites were selected and synthesized under laboratory conditions. Out of five synthesized Pro-DKPs, cyclo(l-Pro-l-Ser) (DKP-6) revealed the best inhibition of fungal pathogens (Fusarium verticillioides and Fusarium fujikuroi) of rice under in vitro conditions with effective doses lower than standard fungicide carbendazim. DKP-6 induced stress on the fungal cell membrane integrity, which was revealed by calcofluor white and propidium iodide assays, endorsed by ultra-microscopic details and soluble protein leakage assays. In vivo seed treatment of infested rice seeds with DKP-6 at 2000 μg/mL for 10 h of seed treatment inflicted best reduction in seed rot and seedling blight with respect to control and carbendazim. Significant enhancement in seedling quality parameters were also observed. The work presented the strong influence of cyclo(l-Pro-l-Ser) as a mycocidal seed treatment agent better than synthetic toxic fungicides for rice.
Molecular capture and conformational change of diketopiperazines containing proline residues by epigallocatechin-3-O-gallate in water
Ishizu, Takashi,Tokunaga, Miku,Fukuda, Moeka,Matsumoto, Mana,Goromaru, Takeshi,Takemoto, Soushi
, p. 585 - 589 (2021/06/06)
The addition of an aqueous solution of diketopiperazine cyclo(Pro-Xxx) (Xxx: amino acid residue) to an aqueous solution of (?)-epigallocatechin-3-O-gallate (EGCg) led to precipitation of the complex of EGCg and cyclo(Pro-Xxx). The molecular capture abilities of cyclo(Pro-Xxx) using EGCg were evaluated by the ratio of the amount of cyclo(Pro-Xxx) included in the precipitates of the complex with EGCg to that of the total cyclo(Pro-Xxx) used. Stronger hydrophobicity of the side chain of the amino acid residue of cyclo(Pro-Xxx) led to a higher molecular capture ability. Furthermore, the molecular capture ability decreased when the side chain of the amino acid residue had a hydrophilic hydroxyl group. When diketopiperazine cyclo(Pro-Xxx), excluding cyclo(D-Pro-L-Ala), was taken into the hydrophobic space formed by the three aromatic A, B, and B′ rings of EGCg, and formed a complex, their conformation was maintained in the hydrophobic space. Based on nuclear Overhauser effect (NOE) measurement, the 3-position methyl group of cyclo(D-Pro-L-Ala) in D2O was axial, whereas that of cyclo(L-Pro-L-Ala) was equatorial. When cyclo(D-Pro-L-Ala) was taken into the hydrophobic space of EGCg and formed a 2:2 complex, its 3-position methyl group changed from the axial position to the equatorial position due to steric hindrance by EGCg.
Cyclols Revisited: Facile Synthesis of Medium-Sized Cyclic Peptides
Mendoza-Sanchez, Rodrigo,Corless, Victoria B.,Nguyen, Q. Nhu N.,Bergeron-Brlek, Milan,Frost, John,Adachi, Shinya,Tantillo, Dean J.,Yudin, Andrei K.
supporting information, p. 13319 - 13322 (2017/10/05)
Medium-sized rings, particularly the corresponding cyclic peptides, are challenging synthetic targets. In the present study, we report an approach to medium-sized cyclic peptides through targeted formation and collapse of cyclol intermediates. This methodology operates on β-amino imides derived from 2,5-diketopiperazines and offers a straightforward transition from frequently examined scaffolds in drug discovery to a rarely visited class of medium-sized rings.
Asymmetric synthesis of 3,4,6-trisubstituted 2,5-diketopiperazines by using dynamic kinetic resolution of α-bromo tertiary acetamides
Baek, Jinho,Kang, Seock Yong,Im, Chan,Park, Yong Sun
, p. 2780 - 2789 (2014/05/06)
A new and efficient method for the asymmetric synthesis of 3,4,6-trisubstituted 2,5-diketopiperazines has been developed. The dynamic kinetic resolution of L-amino-acid-derived α-bromo tertiary amides in the nucleophilic substitution reaction with p-anisi
AGRICULTURAL CHEMICAL CONTAINING 2,5-DIKETOPIPERAZINE DERIVATIVE AS ACTIVE INGREDIENT
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Paragraph 0033, (2013/06/05)
Disclosed herein is an agricultural agent containing a 2,5-diketopiperazine derivative capable of controlling plant diseases and promoting plant growth or an agriculturally acceptable salt thereof as an active ingredient.
A new benzotriazole-mediated stereoflexible gateway to hetero-2,5- diketopiperazines
Monbaliu, Jean-Christophe M.,Hansen, Finn K.,Beagle, Lucas K.,Panzner, Matthew J.,Steel, Peter J.,Todadze, Ekaterina,Stevens, Christian V.,Katritzky, Alan R.
experimental part, p. 2632 - 2638 (2012/04/17)
Open chain Cbz-L-aa1-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5- diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results. Stereoflexible route to DKPs: A convenient, versatile, and flexible benzotriazole-mediated methodology for the synthesis of proline-containing hetero-2,5-diketopiperazines (DKPs) is reported. Depending on the reaction conditions, either cis- or trans-configured DKPs were obtained starting from the same inexpensive l,l-dipeptidoyl benzotriazole key intermediate (see scheme). Kinetics, chiral HPLC, and computational studies forged a background for mechanistic rationalization. Copyright
Design, synthesis, and structure-activity relationship study of bicyclic piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor agonists
Moir, Elizabeth M.,Yoshiizumi, Kazuya,Cairns, Jim,Cowley, Phillip,Ferguson, Morag,Jeremiah, Fiona,Kiyoi, Takao,Morphy, Richard,Tierney, Jason,Wishart, Grant,York, Mark,Baker, James,Cottney, Jean E.,Houghton, Andrea K.,McPhail, Petula,Osprey, Andrew,Walker, Glenn,Adam, Julia M.
scheme or table, p. 7327 - 7330 (2011/01/12)
Bicyclic piperazine derivatives were synthesized as conformationally constrained analogs of N-alkyl piperazines and were found to be potent CB1 receptor agonists. The CB1 receptor agonist activity was dependent upon the absolute configuration of the chiral center of the bicyclic ring system. Although the conformational constraint did not protect the compounds from metabolism by N-dealkylation, several bicyclic analogs were found to be more potent than the unconstrained lead compound. Compound 8b demonstrated potent antinociceptive activity in vivo.
An efficient green synthesis of proline-based cyclic dipeptides under water-mediated catalyst-free conditions
Thajudeen, Habeebullah,Park, Kyungseok,Moon, Surk-Sik,Hong, In Seok
scheme or table, p. 1303 - 1305 (2010/04/29)
l-Proline-based cyclic dipeptides were synthesized from N-Boc-protected dipeptide methyl esters under catalyst-free condition using water as a solvent. One-pot deprotection and cyclization have been used as the key steps, providing an efficient and environmentally friendly approach. Clean reaction conditions, easy isolation, and good yields of cyclic dipeptides are the salient features of the proposed methodology.
