1346773-61-2Relevant academic research and scientific papers
Synthesis of ortho-carboranyl derivatives of (S)-asparagine and (S)-glutamine
Gruzdev,Levit,Olshevskaya,Krasnov
, p. 769 - 776 (2017)
(S)-Asparagine and (S)-glutamine ortho-carboranyl derivatives with free amino and carboxy groups in the α-position were synthesized. By an example of Nγ-(1,2-dicarba-closo-dodecarboran-3-yl)-(S)-glutamine it was demonstrated that the developed synthetic approach carboranyl derivatives of amino acids allowed the preparation of optically pure isomers.
Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease
Thangavelu, Bharani,Mutthamsetty, Vinay,Wang, Qinzhe,Viola, Ronald E.
, p. 870 - 885 (2017/02/05)
Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-L-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms of aspartoacylase to adequately catalyze its breakdown. The membrane-associated enzyme responsible for the synthesis of NAA, aspartate N-acetyltransferase (ANAT), has recently been purified and examined (Wang et al., Prot Expr Purif. 2016;119:11). With the availability, for the first time, of a stable and soluble form of ANAT we can now report the identification of initial inhibitors against this biosynthetic enzyme, obtained from the screening of several focused compound libraries. Two core structures of these moderate binding compounds have subsequently been optimized, with the most potent inhibitors in these series possessing sub-micromolar inhibition constants (Kivalues) against ANAT. Slowing the production of NAA via the inhibition of ANAT will lower the elevated levels of this metabolite and can potentially serve as a treatment option to moderate the symptoms of Canavan disease.
A practical method for selective cleavage of a tert-butoxycarbamoyl N-protective group from N,N-diprotected α-amino acid derivatives using montmorillonite K-10
Hernandez, J. Nicolas,Crisostomo, Fernando R. Pinacho,Martin, Tomas,Martin, Victor S.
, p. 5050 - 5058 (2008/03/18)
A new, practical, and mild procedure for the selective cleavage of a tert-butoxycarbonyl group (Boc) in N-Boc-N-acyl-diprotected amines is described. When applied to α-amino acids, complete integrity of the stereochemistry was observed. The use of N,N-di-Boc-α-amino-δ- and γ-hydroxy esters provided both δ- and γ-lactones in very good yields. The method is based on the use of Montmorillonite K-10 either in CH 2Cl2 at room temperature or in toluene at 65°C and is compatible with the presence of a large range of functional and other protecting groups in the substrates. In most cases virtually pure samples are obtained after filtration and removal of solvents. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
Synthesis of protected γ-carboxyglutamates and γ-acylglutamates by rearrangement of N,N-diacylglutamates
Avent, Anthony G.,Duggan, Heather M. E.,Young, Douglas W.
, p. 2327 - 2332 (2007/10/03)
A new method for γ-acylation of protected glutamic acids, involving intramolecular rearrangement of an acyl urethane, has been devised to prepare the protected γ-carboxyglutamates 7, 9 and 11 and the protected 4-acylglutamates 15 and 22 from N,N-bisurethanes or N-acyl-N-urethanes of general structure 1. When the formylurethane 17 was used in the reaction, then the intermediate 18 in the intramolecular rearrangement was obtained. The Royal Society of Chemistry 2005.
An Approach to Trapping γ-Glutamyl Radical Intermediates Proposed for Vitamin K Dependent Carboxylase: α,β-Methyleneglutamic Acid
Slama, James T.,Satsangi, Rajiv K.,Simmons, Anne,Lynch, Vincent,Bolger, Randall E.,Suttie, John
, p. 824 - 832 (2007/10/02)
The vitamin K dependent carboxylase activates the glutamyl γ-CH of substrate peptides for carboxylation by producing a γ-glutamyl free radical, a γ-glutamyl carbanion, or through a concerted carboxylation.We propose to intercept the putative γ-glutamyl free radical by the intramolecular rearrangement of a substrate containing the α,β-cyclopropane analogue of glutamic acid.The rearrangement of cyclopropylcarbinyl radicals into 2-butenyl radicals is rapid, exothermic, and considered diagnostis of free-radical formation.1-Amino-2-(carboxymethyl)cyclopropane-1-carboxylate, the β-cyclopropane analogue of glutamic acid, was synthesized starting from diethyl α-ketoglutarate.The α-keto ester was first treated with benzonitrile in sulfuric acid, to yield diethyl α,α-dibenzamidoglutarate.The α,α-dibenzamido acid was cleaved to produce the α,β-dehydroamino acid and benzamide on treatment with p-toluenesulfonic acid in hot benzene.Diazomethane addition to the dehydroamino acid resulted in cycloaddition of diazomethane and production of the pyrazoline, which upon irradiation lost N2 to give the protected cyclopropane-containing amino acid analogue.Acid hydrolysis of the N-benzoyl-α,β-methyleneglutamate diethyl ester resulted in the production of the unprotected amino acid, α,β-methyleneglutamic acid, in high yield.A single dehydroamino acid and a single methyleneglutamic acid isomer were produced in this synthesis; both are identified as the Z isomer, the former by NMR using the nuclear Overhauser effect and the latter through X-ray crystallographic analysis of N-benzoyl-α,β-methyleneglutamate diethyl ester.Saponification of a N-protectedmethyleneglutamic acid dialkyl ester using limiting alkali was shown to selectively yield the α-alkyl ester γ-acid.The reaction was used to produce α,β-cyclopropane-containing analogues of the carboxylase substrates N-t-Boc-L-glutamic acid α-benzyl ester and N-benzoyl-L-glutamic acid α-ethyl ester.The cyclpropane-containing analogues were tested and found to be neither substrates for nor inhibitors of the rat liver microsomal vitamin K dependent carboxylase.The inability of the enzyme to recognize these substrate analogues is attributed to the α-alkyl substitution, which apparently abolishes substrate binding.
