10125-07-2Relevant articles and documents
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.
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.
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.
