3025-95-4Relevant articles and documents
Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
supporting information, p. 6949 - 6957 (2020/10/02)
Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.
Preparing method for N-acetyl-L-carnosine
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Paragraph 0031, (2017/03/14)
The invention discloses a preparing method for N-acetyl-L-carnosine and belongs to the technical field of medical intermediates. The method comprises the steps that beta-alanine is subjected to ammonia acetylization to obtain N-acetyl-beta-alanine; N-acetyl-beta-alanine and L-histidine are condensed to obtain N-acetyl-beta-carnosine. N-acetyl-beta-alanine and an acylation reagent react in a non-polar solvent to obtain N-acetyl-beta-alanyl chloride, and L-histidine and organosilane react under the catalyzing of acid to obtain organosilane-protected L-histidine; then organosilane-protected L-histidine and N-acetyl-beta-alanyl chloride are condensed to obtain organosilane-protected N-acetyl-L carnosine, a polar solvent is added to remove protecting groups, and N-acetyl-L-carnosine is obtained through separation and purification. Or, N-acetyl-beta-alanine and L-histidine are condensed under the action of a condensing agent to obatin N-acetyl-L-carnosine.
Direct C-H alkylation of naphthoquinones with amino acids through a revisited Kochi-Anderson radical decarboxylation: Trends in reactivity and applications
Naturale, Guillaume,Lamblin, Marc,Commandeur, Claude,Dessolin, Jean,Felpin, Francois-Xavier
supporting information, p. 5774 - 5788,15 (2020/09/15)
In our ongoing research program into the discovery of new anticancer drugs, we were interested in the preparation of naphthoquinone scaffolds bearing aminoalkyl side-chains. Following this aim, we revisited the Kochi-Anderson radical decarboxylation of amino acids in order to set up a versatile route to the direct functionalization of naphthoquinones. The best reaction conditions were applied to a selected series of compounds in a systematic methodological study which allowed us to establish important trends in reactivity. We found that α-substituted β-amino acids were the most suitable substrates for the radical addition. In contrast, α-amino acids gave modest results. The influence of the amine protecting groups on the reaction outcome has also been studied. This practical procedure allows the introduction of various unsymmetrical moieties, including orthogonally protected linear aminoalkyl chains or chiral dipeptidic chains, and opens the door to a wide scope of easily accessible chemical diversity.
