2886-33-1Relevant articles and documents
Enantiomerically Pure Dibenzyl Esters of l -Aspartic and l -Glutamic Acid
Bolchi, Cristiano,Valoti, Ermanno,Fumagalli, Laura,Straniero, Valentina,Ruggeri, Paola,Pallavicini, Marco
, p. 878 - 883 (2015)
(S)-Dibenzyl aspartate p-toluenesulfonate [(S)-1·TsOH] and (S)-dibenzyl glutamate p-toluenesulfonate [(S)-2·TsOH] were efficiently prepared from the respective l-amino acids and benzyl alcohol with very high yields by using cyclohexane as a water azeotroping solvent instead of benzene, carbon tetrachloride, toluene, or benzyl alcohol itself, as reported in literature methods. Preventively, chiral HPLC methods were developed to determine the enantiomeric excess of the two diesters and DSC analyses were performed on the respective p-toluenesulfonates. With the aid of such investigation tools, we demonstrated that (S)-1·TsOH and (S)-2·TsOH were formed enatiomerically pure in cyclohexane, whereas more or less pronounced racemization occurred both in toluene and in benzyl alcohol. The two one-pot procedures, which did not require crystallization of the product or any other purification step, were accomplished on multigram scale.
p-Toluenesulfonyl Chloride Catalysed Facile Synthesis of O-benzyl-l-amino Acids and Their In Vitro Evaluation
Hegde, Namita,Juvale, Kapil,Prabhakar, Bala
, p. 2129 - 2135 (2020/01/11)
Protection and subsequent deprotection of amino acid functional groups play a key role in regioselective peptide synthesis. For protection, carboxylic acid functional groups are often benzylated using p-toluenesulfonic acid catalysed Fischer-Speier esterification reaction. Such reaction involves in situ water formation, which requires subsequent separation by azeotropic distillation for forward shift of equilibrium. To eliminate the need of this corresponding step requiring additional set-up, current study investigated p-toluenesulfonyl chloride as a reasonable alternative catalyst for facile benzylation of selected mono- and di- carboxylic amino acids. Literature reports that p-toluenesulfonyl chloride not only has a better shelf life but also demonstrates better safety in case of accidental systemic absorption over p-toluenesulfonic acid. As the O-benzyl-l-amino acids are often retained without deprotection to constitute the pharmaceutical peptide systems, synthesized compounds were investigated for their biocompatibility using in vitro cytotoxicity assays.
Stereoselective Synthesis of Tricyclic Diproline Analogues that Mimic a PPII Helix: Structural Consequences of Ring-Size Variation
Soicke, Arne,Reuter, Cédric,Winter, Matthias,Neud?rfl, J?rg-Martin,Schl?rer, Nils,Kühne, Ronald,Schmalz, Hans-Günther
supporting information, p. 6467 - 6480 (2016/02/18)
Polycyclic proline-derived scaffolds (ProMs) have recently demonstrated their value as conformationally defined dipeptide analogs for the modular construction of secondary structure mimetics, specifically interfering with PPII helix-mediated protein-protein interactions. We disclose the stereoselective synthesis of two new tricyclic amino acid scaffolds (ProM-4 and ProM-8) that differ from the first generation scaffold ProM-1 by the size of ring A. Conformational preferences and subtle structural differences of the three homologous scaffolds were analyzed by X-ray crystallography, computational calculations, and NMR spectroscopy. N-tert-butoxycarbonyl(Boc)-3-(1-propenyl)azetidine-2-carboxylic acid was prepared from L-aspartic acid through β-lactam intermediates. The corresponding piperidine-based building block rac-N-Boc-3-vinylpipecolic acid was synthesized by Cu-catalyzed 1,4-addition of vinyl-MgBr to methyl N-Boc-2,3-dehydropipecolate. Target molecules were prepared through peptide coupling of the respective ring A building blocks with cis-5-vinylproline tert-butyl ester and subsequent ring-closing metathesis. Selective deprotection of a tert-butyl carbamate (N-Boc protecting group) in the presence of a tert-butyl ester was achieved with trifluoroacetic acid at 0 C. Two new tricyclic amino acid scaffolds, which differ from the first generation scaffold by the size of ring A, were stereoselectively synthesized. The conformational analysis of the three homologous scaffolds was revealed by NMR spectroscopy.
Polymorphism of amino acid-based dendrons: From organogels to microcrystals
Kuang, Gui-Chao,Teng, Ming-Jun,Jia, Xin-Ru,Chen, Er-Qiang,Wei, Yen
supporting information; experimental part, p. 1163 - 1170 (2011/12/15)
There is a delicate balance for a low-weight molecule to behave as a gelator or crystal. The synthesis of two novel amino acid-based naphthalene-dendrons, Nap-G1 and Nap-G2 is described. Both dendrons display polymorphic properties in organic solvents. Nap-G1 developed a fibrous network with β-sheet architecture in cyclohexane but exhibited a spherulitic network in mixed solvents (chloroform/petroleum ether 1:5, v/v). On the other hand, Nap-G2 acted as an efficient organogelator in chloroform but formed crystalline fibers in relatively high polarity solvents (such as acetone and methanol). Combinations of characterizations have been employed to study the polymorphism. In the balance: Two amino acid-based naphthalene-dendrons display different polymorphic properties in organic solvents. Nap-G1 developed a fibrous network with β-sheet architecture in cyclohexane but exhibited a spherulitic network in mixed solvents while Nap-G2 acts as an efficient organogelator in chloroform but formed crystalline fibers in relatively high polarity solvents (see picture).
Tryptophan-containing dipeptide derivatives as potent PPARγ antagonists: Design, synthesis, biological evaluation, and molecular modeling
Deng, Guanghui,Liu, Zhiguo,Ye, Fei,Luo, Xiaomin,Zhu, Weiliang,Shen, Xu,Liu, Hong,Jiang, Hualiang
experimental part, p. 2699 - 2716 (2009/04/11)
The discovery of peroxisome proliferator-activated receptor γ (PPARγ) antagonists (also termed "selective PPARγ modulators, SPPARγM") is now of a great interest in the treatment of diabetes and obesity. The structure of compound 1a (G3335, Fig. 1), a novel class of PPARγ antagonist, is entirely different from that of other reported PPARγ antagonists. A series of 35 novel analogues (1b-l, 9a-d, 13a-t) were designed, synthesized and evaluated against the agonistic effects exerted by rosiglitazone. These results indicated that most functional groups of 1a were conserved, and six new compounds (1b, 1c, and 9a-d) exhibited strong PPARγ antagonistic activities (IC50 values of 5.2-25.8 μM) against 10 μM rosiglitazone in the promotion of the PPARγ-LBD-CBP (ligand-binding domain and cAMP-response-element binding protein) interaction as investigated by yeast two-hybrid technology based assay. Molecular modeling studies for compounds 1a-d, 1h, 9c-d, and 13a were also presented.
The synthesis of pyrimidin-4-yI substituted a-amino acids. a versatile approach from alkynyl ketones
Adlington, Robert M.,Baldwin, Jack E.,Catterick, David,Pritchard, Garcth J.
, p. 855 - 866 (2007/10/03)
The reaction of amidines with a-amino acid alkynyl ketones is shown to be a versatile route to pyrimidin-4-yl substituted a-amino acids. This route is also applicable to a parallel synthesis approach and has allowed the formation of a range of pyrimidin-4-yl substituted a-amino acids, including the naturally occurring a-amino acid L-lathyrine 4.
Novel ester linked glycosyl amino acids: Convenient building blocks for the synthesis of glycopeptide libraries
Tennant-Eyles, Richard J.,Fairbanks, Antony J.
, p. 391 - 401 (2007/10/03)
The completely orthogonally protected aspartic acid derivative FmocAsp(OBn)O'Bu is readily synthesized on a large scale. Deprotection of the β-carboxylic acid allows coupling to various sugar derivatives via free hydroxyl groups to produce novel glycosyl amino acids. Subsequent deprotection of either the α-acid or nitrogen is achieved cleanly to allow elaboration into an oligopeptide, whilst selective deprotection of PMB protected sugar hydroxyls is also readily achievable. Such novel glycosyl amino acid building blocks may be useful for the combinatorial synthesis of novel glycopeptide libraries.
Chirospecific Synthesis of (1S,3R)-1-Amino-3-(hydroxymethyl)cyclopentane, Precursor for Carbocyclic Nucleoside Synthesis. Dieckmann Cyclization with an α-Amino Acid
Bergmeier, Stephen C.,Cobas, Agustin A.,Rapoport, Henry
, p. 2369 - 2376 (2007/10/02)
Carbocyclic nucleosides are important isosters of nucleosides possessing a variety of antiviral and antineoplastic activities.We report here a new method for the chirospecific synthesis of (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.This compound is a key precursor for the synthesis of some carbocyclic nucleosides.The method involves (1) an improved synthesis of (S)-2-aminoadipic acid; (2) Dieckmann cyclization of this α-amino acid to an aminocyclopentanone; and (3) elaboration of the latter to the target (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.The starting (S)-2-aminoadipic acid δ-methyl ester was prepared enantiomerically pure from (S)-aspartic acid in 51percent overall yield.Dieckmann condensation converted this amino acid to a (methoxycarbonyl)-cyclopentanone, and reduction of the ketone followed by elimination yielded (S)-3--1-(methoxycarbonyl)cyclopentene.Reduction of the double bond gave a mixture of the cis and trans diastereomers.This mixture was converted to a single diastereomer by epimerization and trapping of the cis isomer as (1S,4R)-2-(9-phenylfluoren-9-yl)-2-azabicycloheptan-3-one.Hydrolytic cleavage of the lactam followed by reduction gave (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.
A CONVENIENT NEW SYNTHESIS OF HOMOSERINE LACTONE
Baldwin, J. E.,North, M.,Flinn, A.
, p. 3167 - 3168 (2007/10/02)
N-trityl L-homoserine lactone is synthesised in three steps from L-aspartic acid.
