7536-55-2Relevant articles and documents
Syntheses of Enantiopure 1,2-Ethylenediamines with Tethered Secondary Amines of the Formula H 2NCH 2CH[(CH 2) nNHMe]NH 2(n = 1-4) from α-Amino Acids: New Agents for Asymmetric Catalysis
Kabes, Connor Q.,Gunn, Jack H.,Selbst, Maximilian A.,Lucas, Reagan F.,Gladysz, John A.
, p. 3277 - 3285 (2020/11/02)
Tris(hydrochloride) adducts of the title compounds-are prepared from the inexpensive α-amino acids H 2 N(C=O)CH 2 CH(NH 2)CO 2 H, HO(C=O)(CH 2) n ′ CH(NH 2)CO 2 H (n ′ = 1, 2), and H2 N(CH 2) 4 CH(NH 2)CO 2 H, respectively (steps/overall yield = 5/32, 7/30, 7/33, 5/38). The NH 2 group that is remote from the secondary amine is installed via BH 3 reduction of an amide [-(C=O)NR 2[ derived?-from an α-amino carboxylic acid. The MeNHCH 2 units are introduced by BH 3 reductions of alkyl carbamate [RO(C=O)NHCH 2-; R = Et, t-Bu] or amide [MeHN(C=O)-] moieties.
Studies on the constituents of Helleborus purpurascens: use of derivatives from calix[6]arene, homooxacalix[3]arene and homoazacalix[3]arene as extractant agents for amino acids from the aqueous extract
Franz, M. Heiko,Iorga, Mirela,Maftei, Catalin V.,Maftei, Elena,Neda, Ion
, p. 55 - 72 (2019/12/30)
The task of this work was to investigate the extraction capacity of various calixarenes for free and esterified amino acids from aqueous acid phases. Furthermore, this method was applied to aqueous extracts of Helleborus purpurascens. Generally, it is known that calixarenes can be used as extractants for ammonium compounds due to π-cation and lone pair cation interactions. As first, tert-Butyl-calix[6]arene and derivatives thereof were used. They had already proven their worth in previous investigations. In addition, tert-Butyl-hexahomooxa-calix[3]arene was used also, which can also enter into lone pair cation interactions. In addition to these well-known calixarenes, new calixarenes were produced and tested. Based on the tert-Butyl-hexahomooxa-calix[3]arene, a phosphor(III)bridged derivative was prepared, combining the three aromatic hydroxyl groups to a phosphite. As a seldom-described class of calixarenes, tert-Butyl-hexahomoaza-calix[3]arene derivatives were used. The nitrogen analogues of tert-Butyl-hexahomooxa-calix[3]arene could be produced as N-benzyl derivatives. The structure of the esterified carboxymethylated derivative of N,N′,N″-Tribenzyl-tert-Butyl-hexahomoaza-calix[3]arene could be verified by X-ray structure analysis. It crystallized as a partial cone. The extraction capacity of the described calixarenes was investigated for amino acids from aqueous acidic solutions into an organic phase. For the testing were chosen asparagine, aspartic acid, tyrosine, tryptophane, phenylalanine and pipecolinic acid and their methyl esters. The amino acids and their methyl esters were dissolved in water at different pH values. The calixarenes were dissolved in dichloromethane (DCM) or chloroform. After this preparation, the aqueous acidic amino acid solutions were mixed with the solutions and shaken intensively. In addition, blank values were determined by extracting the aqueous stock solutions of the amino acids and their methyl esters with pure solvents. To determine the extraction rate, the phases were separated and each analysed using GC-FID, partially GC–MS(EI). The evaluation is performed in two ways. On the one hand the depletion in the aqueous phase and on the other hand the content in the organic phase was determined.
Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans
Jovanovic, Milos,Radivojevic, Jelena,O'Connor, Kevin,Blagojevic, Stevan,Begovic, Biljana,Lukic, Vera,Nikodinovic-Runic, Jasmina,Savic, Vladimir
supporting information, p. 209 - 217 (2019/03/23)
Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 μg/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.
Improvement of methods for synthesizing dencichine
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Paragraph 0010; 0011; 0018, (2019/05/28)
The invention discloses improvement of methods for synthesizing dencichine, and belongs to the technical field of medicines and chemical engineering. The improvement has the advantages that the dencichine is white solid, hemostasis effects can be realized by the dencichine by means of shortening the blood coagulation time, the prothrombin time and the like, and accordingly the dencichine is an important medicine, but natural dencichine is low in extraction rate and has small profit spaces; the methods are effective ways for acquiring the dencichine by the aid of chemical synthesis processes and are low in cost, the dencichine can be industrially produced, the reaction cost can be reduced, and important bases can be provided to industrialization.
Substrate specificity of an actively assembling amyloid catalyst
Heier, Jason L.,Mikolajczak, Dorian J.,B?ttcher, Christoph,Koksch, Beate
, (2017/02/05)
In the presence of Zn2+, the catalytic, amyloid-forming peptide Ac-IHIHIQI-NH2, was found to exhibit enhanced selectivity for hydrophobic p-nitrophenyl ester substrates while in the process of self-assembly. As opposed to the substrate p-nitrophenyl acetate, which was more effectively hydrolyzed with Ac-IHIHIQI-NH2 in its fully fibrillar state, the hydrophobic substrate Z-L-Phe-ONp was converted with a second-order rate constant more than 11-times greater when the catalyst was actively assembling. Under such conditions, Z-L-Phe-ONp hydrolysis proceeded at a greater velocity than the more hydrophilic and otherwise more labile ester Boc-L-Asn-ONp. When assembling, the catalyst also showed increased selectivity for the L-enantiomer of Z-Phe-ONp. These findings suggest the occurrence of increased interactions of hydrophobic moieties of the substrate with exposed hydrophobic surfaces of the assembling peptides and present valuable features for future de novo design consideration.
Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides
Pícha, Jan,Budě?ínsky, Milo?,Machá?ková, Kate?ina,Collinsová, Michaela,Jirá?ek, Ji?í
, p. 202 - 214 (2017/04/06)
The rise of CuI-catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives of amino acid as precursors for the synthesis of clicked peptides. However, the use of azido and alkyne amino acids in peptide chemistry is complicated by their high cost. For this reason, we investigated the possibility of the in-house preparation of a set of five Fmoc azido amino acids: β-azido l-alanine and d-alanine, γ-azido l-homoalanine, δ-azido l-ornithine and ω-azido l-lysine. We investigated several reaction pathways described in the literature, suggested several improvements and proposed several alternative routes for the synthesis of these compounds in high purity. Here, we demonstrate that multigram quantities of these Fmoc azido amino acids can be prepared within a week or two and at user-friendly costs. We also incorporated these azido amino acids into several model tripeptides, and we observed the formation of a new elimination product of the azido moiety upon conditions of prolonged couplings with 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/DIPEA. We hope that our detailed synthetic protocols will inspire some peptide chemists to prepare these Fmoc azido acids in their laboratories and will assist them in avoiding the too extensive costs of azidopeptide syntheses. Experimental procedures and/or analytical data for compounds 3–5, 20, 25, 26, 30 and 43–47 are provided in the supporting information.
A BOC - L - the preparation method of the asparagine (by machine translation)
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Paragraph 024; 0025; 0026; 0027, (2017/02/17)
The invention discloses a BOC - L - asparagine of the preparation method, in order to L - asparagine and di-T-n-butyl as raw materials, water as a reaction solvent, in pH 9 - 10 under alkaline conditions generated by the reaction of BOC - L - asparagine, reaction solution acidified to pH 4.0 - 4.5 precipitated BOC - L - asparagine crude, is filtered, washing, drying to obtain the BOC - L - asparagine works. The invention preparation BOC - L - asparagine method has mild reaction conditions, the reaction fast, raw material cost is low, water as a reaction solvent, the follow-up operation is simple, only need to acidify it can separate out BOC - L - asparagine crystal, is favorable to the industrial production, environmental protection, safety coefficient is also relatively high. (by machine translation)
Heating reactions of N-t-Butyloxycarbonyl-Asparagine and related compounds
Munegumi,Akao,Kawatu,Yamada,Harada
, p. 6541 - 6548 (2015/02/19)
N-t-Butyloxycarbonyl-amino acids (Boc-) are labile on heating to afford free amino acids, but Boc-aspartic acid gives a kind of polypeptide. This chemical feature of Boc-aspartic acid may be caused by dehydration between two carboxyl groups as well as the formation of a free amino group. Boc-Asparagine may have a similar reactivity to Boc-aspartic acid. This research describes polypeptide formation by heating Boc-asparagine and its isomer Boc-aspartic acid amide.
Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules
Vizcaino, Maria I.,Engel, Philipp,Trautman, Eric,Crawford, Jason M.
supporting information, p. 9244 - 9247 (2014/07/21)
The gene cluster responsible for synthesis of the unknown molecule colibactin has been identified in mutualistic and pathogenic Escherichia coli. The pathway endows its producer with a long-term persistence phenotype in the human bowel, a probiotic activity used in the treatment of ulcerative colitis, and a carcinogenic activity under host inflammatory conditions. To date, functional small molecules from this pathway have not been reported. Here we implemented a comparative metabolomics and targeted structural network analyses approach to identify a catalog of small molecules dependent on the colibactin pathway from the meningitis isolate E. coli IHE3034 and the probiotic E. coli Nissle 1917. The structures of 10 pathway-dependent small molecules are proposed based on structural characterizations and network relationships. The network will provide a roadmap for the structural and functional elucidation of a variety of other small molecules encoded by the pathway. From the characterized small molecule set, in vitro bacterial growth inhibitory and mammalian CNS receptor antagonist activities are presented.
Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor
Incerti, Matteo,Tognolini, Massimiliano,Russo, Simonetta,Pala, Daniele,Giorgio, Carmine,Hassan-Mohamed, Iftiin,Noberini, Roberta,Pasquale, Elena B.,Vicini, Paola,Piersanti, Silvia,Rivara, Silvia,Barocelli, Elisabetta,Mor, Marco,Lodola, Alessio
supporting information, p. 2936 - 2947 (2013/05/22)
The Eph receptor-ephrin system is an emerging target for the development of novel antiangiogenetic agents. We recently identified lithocholic acid (LCA) as a small molecule able to block EphA2-dependent signals in cancer cells, suggesting that its (5β)-cholan-24-oic acid scaffold can be used as a template to design a new generation of improved EphA2 antagonists. Here, we report the design and synthesis of an extended set of LCA derivatives obtained by conjugation of its carboxyl group with different α-amino acids. Structure-activity relationships indicate that the presence of a lipophilic amino acid side chain is fundamental to achieve good potencies. The l-Trp derivative (20, PCM126) was the most potent antagonist of the series disrupting EphA2-ephrinA1 interaction and blocking EphA2 phosphorylation in prostate cancer cells at low μM concentrations, thus being significantly more potent than LCA. Compound 20 is among the most potent small-molecule antagonists of the EphA2 receptor.
