- Efficient synthesis of (S,S)-ethambutol from L-methionine
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Starting from readily available amino acid L-methionine, an efficient synthesis of the tuberculostatic agent (S,S)-ethambutol has been developed. The key steps in the synthetic sequence involve: dimerization of methionine methyl ester through oxalyl diamide formation, Raney nickel desulfurization of the terminal thiomethyl groups, and a one-pot exhaustive reduction of the oxalamide and the diester functionalities to afford the desired enantiopure (S,S)-ethambutol in good overall yield.
- Stauffer, Christina S,Datta, Apurba
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- Photooxidation of Methionine Derivatives by the 4-Carboxybenzophenone Triplet State in Aqueous Solution. Intracomplex Proton Transfer Involving the Amino Group
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Oxidation of the triplet state of 4-carboxybenzophenone (CB) by a series of five substituted methionines and three methionine-containing dipeptides was monitored under laser flash photolysis conditions in aqueous solution. Spectral resolution techniques were employed to follow the concentration profiles of the intermediates formed from the quenching events. From these concentration profiles, quantum yields for the intermediates were determined. Branching ratios were evaluated for the decay of the charge-transfer complex by the competing processes of back electron transfer, proton transfer and escape of radical ions. The relative prominence of these processes was discussed in terms of the proton-transfer tendencies of the nominal sulfur-radical-cationic species. A systematic decrease was observed in the quantum yields for the escape of radical ions along with a correlated increase in the proton-transfer yields. The enhanced propensity of the sulfur radical cations to deprotonate is due to deprotonation at the carbons adjacent to the sulfur-cationic site and at the unsubstituted amino groups when present. This scheme was supported by an observed decrease in the yields of dimeric sulfur radical cations with an increase in the electron-withdrawing abilities of the substituents, making the radical-cationic species stronger acids. The involvement of protons on the amino groups was implicated by the correlation of the quantum yields of ketyl radical formation in the photo-chemistry experiments with the rate constants for the reaction of the CB radical anion with the sulfur-containing substrates in pulse radiolysis experiments.
- Hug, Gordon L.,Bobrowski, Krzysztof,Kozubek, Halina,Marciniak, Bronislaw
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- One-pot selective cleavage of prenyl carbamates using iodine in methanol followed by zinc
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The prenyloxycarbonyl (Preoc) moiety was efficiently removed from carbamates to provde the corresponding amines in good to excellent yields (63-88 percent) by using iodine in methanol followed by treatment of the resulting β-methoxyiodides by zinc powder. The reaction conditions are compatible with the presence of a number of functional groups such as Boc and Cbz carbamates, sulfides, double bonds, indoles and aromatic methyl ethers.
- Vatele, Jean-Michel
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- Alternative and chemoselective deprotection of the α-amino and carboxy functions of N-Fmoc-amino acid and N-Fmoc-dipeptide methyl esters by modulation of the molar ratio in the AlCl3/N,N-dimethylaniline reagent system
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The amino and carboxy functions in N-Fmoc-α-amino acid and N-Fmoc-peptide methyl esters can be alternatively and chemoselectively deprotected by treatment with the reagent system AlCl3/N,N- dimethylaniline (DMA). The chemoselectivity of the process is controlled by modulating the relative molar ratio of the Lewis acid and DMA. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Di Gioia, Maria Luisa,Leggio, Antonella,Le Pera, Adolfo,Liguori, Angelo,Perri, Francesca,Siciliano, Carlo
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- NMR determinations of the absolute configuration of α-chiral primary amines
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(Figure presented) We have established a methodology to determine the absolute configuration of α-chiral primary amines by derivatization to the corresponding imines with each enantiomer of 2′-methoxy-1,1′- binaphthalene-8-carbaldehyde (1). This methodology proceeds on the basis of modified Moshers method, and sufficiently large ΔδR S values can be obtained to elucidate the stereochemistry of the amines.
- Fukui, Hiroki,Fukushi, Yukiharu
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- Using ionic liquid [EMIM][CH3COO] as an enzyme-'friendly' co-solvent for resolution of amino acids
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An ionic liquid (IL), 1-ethyl-3-methylimidazolium acetate [EMIM][CH3COO], was used in 0-4.0 M (~60% IL, v/v), as a nonvolatile organic medium for the enzymatic resolution of amino acids. When dl-phenylalanine methyl ester was studied as a model substrate, high enantiomeric excesses (ee) of l-amino acid were obtained in all ionic concentrations; however, lower yields were observed at high IL concentrations. This IL is more enzyme-'friendly' than the hydrophilic organic solvent acetonitrile and those ILs containing chaotropic anions (such as [EMIM][OTs]). Among three proteases and two lipases investigated, lyophilized Bacillus licheniformis protease exhibited the best enantioselectivity and activity. Highly enantioselective resolutions were also produced for several other amino acids in 2.0 M IL. Interestingly, high ee were also found in deuterium oxide (D2O) rather than in ordinary water, and a further enhancement was achieved with the co-existence of [EMIM][CH3COO]. The heavy water effect was explained in terms of protein stabilization by D2O. The secondary structural changes of enzyme in various media were interpreted by the second derivatives of FT-IR spectra.
- Zhao, Hua,Jackson, Lee,Song, Zhiyan,Olubajo, Olarongbe
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- Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors
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Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line.
- Yang, Dezhi,Wang, Peng,Liu, Jianzhen,Xing, Hualu,Liu, Yang,Xie, Wencheng,Zhao, Guisen
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- Continuous flow heterogeneous catalytic reductive aminations under aqueous micellar conditions enabled by an oscillatory plug flow reactor
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Despite the fact that continuous flow processing exhibits well-established technical advances, aqueous micellar chemistry, a field that has proven extremely useful in shifting organic synthesis to sustainable water-based media, has mostly been explored under conventional batch-based conditions. This is particularly because of the fact that the reliable handling of slurries and suspensions in flow has been considered as a significant technical challenge. Herein, we demonstrate that the strategic application of an oscillatory plug flow reactor enables heterogeneous catalytic reductive aminations in aqueous micellar media enhancing mass transport and facilitating process simplicity, stability and scalability. The micellar flow process enabled a broad range of substrates, including amino acid derivatives, to be successfully transformed under reasonably mild conditions utilizing only very low amounts of Pd/C as a readily available heterogeneous catalyst. The preparative capabilities of the process along with the recyclability of the heterogenous catalyst and the aqueous reaction media were also demonstrated. This journal is
- ?tv?s, Sándor B.,Buchholcz, Balázs,Darvas, Ferenc,Kappe, C. Oliver,Novák, Zoltán,Sipos, Gellért,Wernik, Michaela
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supporting information
p. 5625 - 5632
(2021/08/16)
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- Discovery of γ-Lactam alkaloid derivatives as potential fungicidal agents targeting steroid biosynthesis
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Biological control of plant pathogens is considered as one of the green and effective technologies using beneficial microorganisms or microbial secondary metabolites against plant diseases, and so microbial natural products have played important roles in the research and development of new and green agrochemicals. To explore the potential applications for natural γ-lactam alkaloids and their derivatives, 26 γ-lactams that have flexible substituent patterns were synthesized and characterized, and their in vitro antifungal activities against eight kinds of plant pathogens belonging to oomycetes, basidiomycetes, and deuteromycetes were fully evaluated. In addition, the high potential compounds were further tested using an in vivo assay against Phytophthora blight of pepper to verify a practical application for controlling oomycete diseases. The potential modes of action for compound D1 against Phytophthora capsici were also investigated using microscopic technology (optical microscopy, scanning electron microscopy, and transmission electron microscopy) and label-free quantitative proteomics analysis. The results demonstrated that compound D1 may be a potential novel fungicidal agent against oomycete diseases (EC50 = 4.9748 μg·mL-1 for P. capsici and EC50 = 5.1602 μg·mL-1 for Pythium aphanidermatum) that can act on steroid biosynthesis, which can provide a certain theoretical basis for the development of natural lactam derivatives as potential antifungal agents.
- Cao, Xiufang,Huang, Daye,Huang, Wenbo,Ke, Shaoyong,Song, Di,Wang, Shuangshuang
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p. 14438 - 14451
(2020/12/23)
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- Synthesis and evaluation of antitumor activities of 4-selenopyrimidine derivatives
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Pyrimidine antimetabolic agents are the essential drugs in treatment of various tumors. Novel synthesis and biological evaluation of the pyrimidine derivatives incorporating selenium element and amino acid carrier as potential antitumor agents have not been tried and studied. Based on the biological significance of pyrimidine structure, these two additional elemental fragments maybe enhance the antitumor effect and reduce toxic side effects of pyrimidine agents. The aim of this paper is to synthesis a series of 4-selenopyrimidine derivatives in order to find more potent lead compounds against cancer. In this study, 12 new 4-selenopyrimidine derivatives that are unstable in acidic solutions but very stable in alkaline and neutral solutions avoiding light were synthesized, and the antitumor activities on HepG2 cell lines of these compounds were evaluated by MTT assay. The results have shown that these compounds could reduce the proliferation of HepG2 cells in a dose-dependent fashion, and the inhibitory activity of compounds a6 was greater than that of positive control 5-fluorouracil (5-FU), the IC50 for a6 was 3.63 μM. In the comprehensive analysis of the structure–activity relationship, we could draw the antitumor effect of selenouracil derivatives is stronger than those of selenothymine derivatives. These results suggest that the substituent groups of selenium element and amino acid on the pyrimidine derivatives are vital for their antitumor activities on HepG2 cells.
- Shi, Mingxing,Wang, Libo,Zhang, Long,Wang, Kexin,Zhang, Hualin,Wang, Yajing,Li, Chang,Han, Weina
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- N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
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Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
- Bárta, Pavel,Dole?al, Martin,Horá?ek, Ond?ej,Jand'Ourek, Ond?ej,Janou?ek, Ji?í,Juhás, Martin,Kone?ná, Klára,Ku?era, Radim,Ku?erová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Paterová, Pavla,Zitko, Jan
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- NOVEL PYRROLO-LACTONE AND PYRROLE COMPOUNDS INDUCING CELLULAR GLUTATHIONE RECOVERY EFFECT AGAINST REACTIVE OXYGEN SPECIES, AND METHOD FOR PREPARING THE SAME
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The present invention provides: a novel pyrrolo-lactone compound, which can be used as an improved pain therapeutic agent containing various substituents by using glucose and ribose as reducing sugars and conducting a reaction with various kinds of natural and unnatural amino acids; and novel pyrrolo compounds produced during a process of manufacturing the same. The novel pyrrolo-lactone and pyrrole compounds are substances which can be used as improved pain therapeutic agent by having increased restoration ability of glutathione in living cells against reactive oxygen species.COPYRIGHT KIPO 2019
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Paragraph 0102-0106; 0117; 0121; 0146; 0150
(2019/05/10)
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- Genetic Incorporation of Olefin Cross-Metathesis Reaction Tags for Protein Modification
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Olefin cross-metathesis (CM) is a viable reaction for the modification of alkene-containing proteins. Although allyl sulfide or selenide side-chain motifs in proteins can critically enhance the rate of CM reactions, no efficient method for their site-selective genetic incorporation into proteins has been reported to date. Here, through the systematic evaluation of olefin-bearing unnatural amino acids for their metabolic incorporation, we have discovered S-allylhomocysteine (Ahc) as a genetically encodable Met analogue that is not only processed by translational cellular machinery but also a privileged CM substrate residue in proteins. In this way, Ahc was used for efficient Met codon reassignment in a Met-auxotrophic strain of E. coli (B834 (DE3)) as well as metabolic labeling of protein in human cells and was reactive toward CM in several representative proteins. This expands the use of CM in the toolkit for "tag-and-modify" functionalization of proteins.
- Bhushan, Bhaskar,Lin, Yuya A.,Bak, Martin,Phanumartwiwath, Anuchit,Yang, Nan,Bilyard, Matthew K.,Tanaka, Tomonari,Hudson, Kieran L.,Lercher, Lukas,Stegmann, Monika,Mohammed, Shabaz,Davis, Benjamin G.
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supporting information
p. 14599 - 14603
(2018/11/21)
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- Unlocking the potential of phenacyl protecting groups: CO2-based formation and photocatalytic release of caged amines
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Orthogonal protection and deprotection of amines remain important tools in synthetic design as well as in chemical biology and material research applications. A robust, highly efficient, and sustainable method for the formation of phenacyl-based carbamate esters was developed using CO2 for the in situ preparation of the intermediate carbamates. Our mild and broadly applicable protocol allows for the formation of phenacyl urethanes of anilines, primary amines, including amino acids, and secondary amines in high to excellent yields. Moreover, we demonstrate the utility by a mild and convenient photocatalytic deprotection protocol using visible light. A key feature of the [Ru(bpy)3](PF6)2-catalyzed method is the use of ascorbic acid as reductive quencher in a neutral, buffered, two-phase acetonitrile/water mixture, granting fast and highly selective deprotection for all presented examples.
- Speckmeier, Elisabeth,Klimkait, Michael,Zeitler, Kirsten
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p. 3738 - 3745
(2018/04/14)
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- MOLECULAR GELATORS FOR CONTAINING OIL SPILLAGE
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The application relates to peptide-based compounds of Formula I such as the compound of Formula II, methods of making such compounds, gels comprising such compounds, methods of making gels, methods of using such compounds for containing the spill of a hydrocarbon, and methods for reclaiming solvent from gels comprising such compounds.
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Paragraph 0054; 0055
(2016/12/22)
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- Overcoming mutagenicity and ion channel activity: Optimization of selective spleen tyrosine kinase inhibitors
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Development of a series of highly kinome-selective spleen tyrosine kinase (Syk) inhibitors with favorable druglike properties is described. Early leads were discovered through X-ray crystallographic analysis, and a systematic survey of cores within a selected chemical space focused on ligand binding efficiency. Attenuation of hERG ion channel activity inherent within the initial chemotype was guided through modulation of physicochemical properties including log D, PSA, and pKa. PSA proved most effective for prospective compound design. Further profiling of an advanced compound revealed bacterial mutagenicity in the Ames test using TA97a Salmonella strain, and subsequent study demonstrated that this mutagenicity was pervasive throughout the series. Identification of intercalation as a likely mechanism for the mutagenicity-enabled modification of the core scaffold. Implementation of a DNA binding assay as a prescreen and models in DNA allowed resolution of the mutagenicity risk, affording molecules with favorable potency, selectivity, pharmacokinetic, and off-target profiles.
- Ellis, J. Michael,Altman, Michael D.,Bass, Alan,Butcher, John W.,Byford, Alan J.,Donofrio, Anthony,Galloway, Sheila,Haidle, Andrew M.,Jewell, James,Kelly, Nancy,Leccese, Erica K.,Lee, Sandra,Maddess, Matthew,Miller, J. Richard,Moy, Lily Y.,Osimboni, Ekundayo,Otte, Ryan D.,Reddy, M. Vijay,Spencer, Kerrie,Sun, Binyuan,Vincent, Stella H.,Ward, Gwendolyn J.,Woo, Grace H. C.,Yang, Chiming,Houshyar, Hani,Northrup, Alan B.
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supporting information
p. 1929 - 1939
(2015/04/27)
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- INHIBITORS OF THE FIBROBLAST GROWTH FACTOR RECEPTOR
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Described herein are inhibitors of FGFR-4, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions.
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Paragraph 0270; 0271; 0272
(2015/05/05)
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- A convergent synthesis of carbocyclic sinefungin and its C-5 epimer
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A convergent synthesis of carbocyclic sinefungin (2), its C-5 epimer 3a, and adenine-modified derivative 3b is described. The key features of our approach include the use of commercially available L-methionine and readily available (1R,4S)-4-hydroxy-2-cyclopentenyl acetate as starting materials, a cross-metathesis reaction, an enzymatic kinetic resolution, and a Staudinger reduction. The current synthesis is flexible and, therefore, provides convenient access to the synthesis of various carbocyclic sinefungin analogues for biological evaluation. A convergent synthesis of carbocyclic sinefungin (2), its C-5 epimer 3a, and adenine-modified derivative 3b is described. The key features of this approach include the use of commercially available L-methionine and readily available (1R,4S)-4-hydroxy-2-cyclopentenyl acetate, a cross-metathesis reaction, an enzymatic kinetic resolution, and a Staudinger reduction.
- Ghosh, Arun K.,Lv, Kai
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p. 6761 - 6768
(2016/02/18)
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- A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
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An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.
- Bera, Saurav,Panda, Gautam
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p. 3976 - 3985
(2014/06/09)
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- Enantioselective friedel-crafts alkylation of pyrrole with chalcones catalyzed by a dinuclear zinc catalyst
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A highly enantioselective Friedel-Crafts (F-C) alkylation of pyrrole with a wide range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of diethylzinc. A series of β-pyrrole-substituted dihydrochalcones were usually formed mostly in excellent yields (up to 99%) and excellent enantioselectivity [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under mild conditions. The absolute stereochemistry of the products was determined to be the S-configuration by X-ray crystallographic analysis of 13g. Meanwhile, a weak negative nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible mechanism was proposed to explain the origin of the asymmetric induction.
- Hua, Yuan-Zhao,Han, Xing-Wang,Yang, Xiao-Chao,Song, Xixi,Wang, Min-Can,Chang, Jun-Biao
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p. 11690 - 11699
(2015/01/16)
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- In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
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The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
- Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
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supporting information
p. 6824 - 6830
(2013/06/26)
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- 2-PYRIDYL CARBOXAMIDE-CONTAINING SPLEEN TYROSINE KINASE (SYK) INHIBITORS
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The invention provides certain 2-pyridyl carboxamide-containing compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein A and B are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk) kinase.
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Paragraph 00311
(2013/04/24)
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- Alternative substrates selective for S-adenosylmethionine synthetases from pathogenic bacteria
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S-adenosyl-L-methionine (AdoMet) synthetase catalyzes the production of AdoMet, the major biological methyl donor and source of methylene, amino, ribosyl, and aminopropyl groups in the metabolism of all known organism. In addition to these essential functions, AdoMet can also serve as the precursor for two different families of quorum sensing molecules that trigger virulence in Gram-negative human pathogenic bacteria. The enzyme responsible for AdoMet biosynthesis has been cloned, expressed and purified from several of these infectious bacteria. AdoMet synthetase (MAT) from Neisseria meningitidis shows similar kinetic parameters to the previously characterized Escherichia coli enzyme, while the Pseudomonas aeruginosa enzyme has a decreased catalytic efficiency for its MgATP substrate. In contrast, the more distantly related MAT from Campylobacter jejuni has an altered quaternary structure and possesses a higher catalytic turnover than the more closely related family members. Methionine analogs have been examined to delineate the substrate specificity of these enzyme forms, and several alternative substrates have been identified with the potential to block quorum sensing while still serving as precursors for essential methyl donation and radical generation reactions.
- Zano, Stephen P.,Bhansali, Pravin,Luniwal, Amarjit,Viola, Ronald E.
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- PROCESS FOR PRODUCING SULFUR-CONTAINING AMINO ACIDS
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The present invention relates to a process for producing a sulfur-containing amino acid, comprising a step of oxidizing a 2-aminoethanol compound having, at position 2, a sulfur-containing hydrocarbon group having 1 to 24 carbon atoms in the presence of copper and water.
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Page/Page column 16
(2011/10/31)
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- Comparison of liquid chromatography-isotope ratio mass spectrometry (LC/IRMS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) for the determination of collagen amino acid δ13C values for palaeodietary and palaeoecological reconstruction
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Results are presented of a comparison of the amino acid (AA) δ13C values obtained by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) and liquid chromatography-isotope ratio mass spectrometry (LC/IRMS). Although the primary focus was the compound-specific stable carbon isotope analysis of bone collagen AAs, because of its growing application for palaeodietary and palaeoecological reconstruction, the results are relevant to any field where AA δ13C values are required. We compare LC/IRMS with the most up-to-date GC/C/IRMS method using N-acetyl methyl ester (NACME) AA derivatives. This comparison involves the analysis of standard AAs and hydrolysates of archaeological human bone collagen, which have been previously investigated as N-trifluoroacetyl isopropyl esters (TFA/IP). It was observed that, although GC/C/IRMS analyses required less sample, LC/IRMS permitted the analysis of a wider range of AAs, particularly those not amenable to GC analysis (e.g. arginine). Accordingly, reconstructed bulk δ13C values based on LC/IRMS-derived δ13C values were closer to the EA/IRMS-derived δ13C values than those based on GC/C/IRMS values. The analytical errors for LC/IRMS AA δ13C values were lower than GC/C/IRMS determinations. Inconsistencies in the δ13C values of the TFA/IP derivatives compared with the NACME- and LC/IRMS-derived δ13C values suggest inherent problems with the use of TFA/IP derivatives, resulting from: (i) inefficient sample combustion, and/or (ii) differences in the intra-molecular distribution of δ13C values between AAs, which are manifested by incomplete combustion. Close similarities between the NACME AA δ13C values and the LC/IRMS-derived δ13C values suggest that the TFA/IP derivatives should be abandoned for the natural abundance determinations of AA δ13C values.
- Dunn, Philip J. H.,Honch, Noah V.,Evershed, Richard P.
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experimental part
p. 2995 - 3011
(2012/05/20)
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- Simple methodology for the preparation of amino alcohols from amino acid esters using nabh4-methanol in THF
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Amino alcohols constitute a very useful and versatile class of organic compounds, with important applications in synthetic and medicinal chemistry. However, in most of the procedures described in the literature for the obtainment of these compounds, considerable limitations can be found, such as drastic conditions, long time reactions, poor yields, and purification problems. The present article describes a methodology that gives amino alcohols and N-protected amino alcohols based on the reduction of amino acid esters under mild conditions, employing NaBH4 in the presence of methanol. The reactions occurred in a short time (15-20min) and provide yields of 50-95%.
- Goncalves,Pinheiro,Da Silva,Da Costa,Kaiser,De Souza
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body text
p. 1276 - 1281
(2011/05/04)
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- PROCESS FOR PRODUCING METHIONINE
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The present invention relates to a process for producing methionine, comprising a first step of reacting 2-amino-3-buten-1-ol with methanethiol, and a second step of oxidizing 2-amino-4-methylthio-1-butanol obtained in the first step. The present invention also relates to a process for producing 2-amino-4-methylthio-1-butanol, comprising a step of reacting 2-amino-3-buten-1-ol with methanethiol.
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Page/Page column 59; 61-65
(2011/12/14)
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- Enantiomeric resolution of α-amino acid derivatives on two diastereomeric chiral stationary phases based on chiral crown ethers incorporating two different chiral units
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Two diastereomeric chiral stationary phases (CSPs) were applied to the liquid chromatographic resolution of various racemic a-amino methyl esters, α-amino N,N-diethylamides and α-amino N-propylamides. The CSP incorporating (R)-3,3' -diphenyl-1,1' -binaphtyl and (R,R)-tartaric acid unit as chiral barriers did not show any chiral recognition. In contrast, the CSP incorporating (R)-3,3'-diphenyl-1,1'-binaphtyl and (S,S)-tartaric acid unit as chiral barriers was found to show excellent chiral recognition especially for the two enantiomers of a-amino N-propylamides. Some of a-amino methyl esters and α-amino N,N-diethylamides were also resolved on the CSP incorporating (R)-3,3'-diphenyl-1,1'-binaphtyl and (S,S)-tartaric acid unit. From these results it was concluded that the two chiral units composing the diastereomeric CSPs can show "matched" or "mismatched" effect on the chiral recognition according to their absolute stereochemistry.
- Kim, Hee Jin,Choi, Hee Jung,Cho, Yoon Jae,Hyun, Myung Ho
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body text
p. 1551 - 1554
(2010/10/20)
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- A class of novel Schiff's bases: Synthesis, therapeutic action for chronic pain, anti-inflammation and 3D QSAR analysis
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To discover analgesics for treating chronic pain 17 novel Schiff's bases, N,N′-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 μmol/kg of these Schiff's bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 μmol/kg of these Schiff's bases exhibited desirable anti-inflammation. Thus the present Schiff's bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff's bases on the analgesic activity was explained with 3D QSAR.
- Zhou, Yinjian,Zhao, Ming,Wu, Yingting,Li, Chunyu,Wu, Jianhui,Zheng, Meiqing,Peng, Li,Peng, Shiqi
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experimental part
p. 2165 - 2172
(2010/05/18)
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- Synthesis and electrochemical studies of disubstituted ferrocene/dipeptide conjugates with sulfur-containing side chains
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A series of 1 1'-disubstituted ferrocenoyl peptides incorporating dipeptide sidearms has been synthesized and studied electrochemically. The target peptides include ferrocene as an electrochemical reporter, sulfur-containing amino acids (L-methionine, S-methyl-L-cysteine, S-trityl-L-cysteine, S-benzhydryl-L- cysteine) as metal binding agents, and amino acids with non-polar side chains (L-alanine, L-valine, L-phenylalanine) as spacers between reporter and metal binding groups. Ferrocene/dipeptide conjugates were prepared using solution phase peptide synthesis methods employing a BOC-protecting group strategy and HBTU- (O-(benzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate) mediated peptide coupling. The electrochemical properties of these 1, 1'-substituted ferrocenoyl peptides have been characterized using cyclic voltammetry. All exhibit fully reversible one electron oxidation steps; forward sweep half wave peaks (EF), reverse sweep half wave peaks (ER), peak separations (DEP) and half wave potentials (E1/2) are reported. Finally, towards the goal of utilizing ferrocenoyl peptides to detect heavy metals in solution, the response of these ferrocene/dipeptide conjugates to metal cations (zinc(II), mercury(II), cadmium(II), lead(II), silver(I)) has been examined. Monitoring changes in the potential of the Fe(II)/Fe(III) redox couple to follow peptide/metal interactions, we have probed the influence of the spacer unit between the redox reporter and the metal-binding amino acid, and shown that these systems respond to mercury(II) more strongly than to other heavy metal ions.
- Scully, Conor C.G.,Rutledge, Peter J.
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scheme or table
p. 5653 - 5659
(2010/10/02)
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- 2,2-Bis(ethoxycarbonyl)vinyl (BECV) as a versatile amine protecting group for selective functional-group transformations
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A 2,2-Bis(ethoxycarbonyl) vinyl- (BECV) group was used for the selective protection of amines at room temperature in the presence of potentially interfering functional groups such as OH, SH, COOH as well as other NH 2 groups. Several functional group transformations such as esterification, O-alkylation, O-acylation, N-alkylation, N-acylation, S-alkylation can selectively be carried out in the presence of the BECV group. The selective deprotection of the BECV group was achieved in a short time using ethylenediamine at room temperature while several other functional groups such as benzoate, aliphatic esters, amides and ethers remain intact. The BECV group shows orthogonal stability against the common protecting groups such as Fmoc, Cbz and Boc.
- Ilangovan, Andivelu,Kumar, Rajendran Ganesh
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supporting information; experimental part
p. 2938 - 2943
(2010/07/02)
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- N-benzyl-protection of amino acid derivatives by reductive alkylation with α-picoline-borane
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A convenient method for N-protection of amino acid derivatives with a benzyl group by reductive alkylation of amino acid derivatives with α-picoline-borane is described. Amino acid esters or amino alcohols were treated with aryl aldehydes in methanol/acetic acid in the presence of -picoline-borane to give N-benzyl-protected amino acid derivatives in good yields. Georg Thieme Verlag Stuttgart - New York.
- Kawase, Yasushi,Yamagishi, Takehiro,Kutsuma, Teruo,Kataoka, Tadashi,Ueda, Kimio,Iwakuma, Takeo,Nakata, Tadashi,Yokomatsu, Tsutomu
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experimental part
p. 1673 - 1677
(2010/06/22)
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- SUBSTITUTED AMINO ALCOHOLS
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Disclosed herein are substituted amino alcohol anti-mycobacterial agents and/or chelation therapy agents of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 25
(2009/04/24)
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- Potential anti-inflammatory actions of the elmiric (lipoamino) acids
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A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production, and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells were the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ2 with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them.
- Burstein, Sumner H.,Adams, Jeffrey K.,Bradshaw, Heather B.,Fraioli, Cristian,Rossetti, Ronald G.,Salmonsen, Rebecca A.,Shaw, John W.,Walker, J. Michael,Zipkin, Robert E.,Zurier, Robert B.
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p. 3345 - 3355
(2008/02/09)
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- A novel naphthylmethyleneimino-type photocleavable protecting group for primary amines
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A novel naphthylmethyleneimino-type protecting group for aliphatic and aromatic primary amines including α-amino acids was devised and its introduction was accomplished in good to excellent yields. This type of protecting group was found to be cleanly removed photochemically to regenerate the primary amines in good to high yields, regardless of steric and electronic properties. Georg Thieme Verlag Stuttgart.
- Igarashi, Tetsutaro,Shimokawa, Masaru,Iwasaki, Miyuki,Nagata, Kensaku,Fujii, Masato,Sakurai, Tadamitsu
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p. 1436 - 1440
(2008/02/13)
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- Enantioselective Synthesis of Non-Natural Aromatic α-Amino Acids
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We present two complementary methods for the stereoselective synthesis of non-natural α-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C2 or C3 linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the α-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.
- Krebs, Andreas,Ludwig, Verena,Pfizer, Jose,Duerner, Gerd,Goebel, Michael W.
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p. 544 - 553
(2007/10/03)
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- Prenyl carbamates: Preparation and deprotection
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Prenyloxycarbonylimidazole (PreocIm) and prenyl p-nitrophenyl carbonate (PreocOC6H4p-NO2), two substitutes for the unstable prenyl chloroformate, allowed an efficient introduction of the prenyloxycarbonyl group to a variety of primary and secondary amines. Deprotection of prenyl carbamates was readily achieved by, first their conversion to 2-iodo-3-methoxy-3-methylbutyl carbamates with iodine in methanol followed by reductive β-elimination with zinc powder. These reaction conditions are compatible with the presence of a number of functional groups such as Boc and Cbz carbamates, sulfides, double bonds, indoles and aromatic ethers.
- Vatèle, Jean-Michel
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p. 4251 - 4260
(2007/10/03)
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- Mild regeneration of the carboxylic group of amino acid alkyl esters by aqueous methanolic sodium hydrogen carbonate via 5-oxazolidinones
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A simple racemization-free procedure allows the regeneration of the carboxylic acid group of amino acid alkyl esters by way of an intermediate 5-oxazolidinone which is hydrolyzed by treatment with sodium hydrogen carbonate in aqueous methanol.
- Allevi, Pietro,Anastasia, Mario
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p. 7663 - 7665
(2007/10/03)
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- Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers
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The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in which substituents have been introduced into the 3- and 4-positions of the lactone ring. These analogues have been screened for their ability to activate and inhibit a Vibrio fischeri LuxI/LuxR-derived quorum sensing reporter system.
- Olsen,Severinsen,Rasmussen,Hentzer,Givskov,Nielsen
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p. 325 - 328
(2007/10/03)
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- A mild and convenient procedure for the esterification of amino acids
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Chiral amino acids are esterified in high yield and purity at room temperature by stirring with amberlyst-15 in alcohols.
- Anand, Ramesh C.,Vimal
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p. 1963 - 1965
(2007/10/03)
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- The Pent-4-enoyl Group: A Novel Amine-Protecting Group That Is Readily Cleaved under Mild Conditions
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Primary and secondary amines are readily protected as N-pent-4-enoyl derivatives, the resulting N-pent-4-enamides being usually highly crystalline.Deprotection is rapidly and efficiently effected under mild conditions by treatment with 3 equiv of iodine in aqueous THF solution.Although an oxidizing medium, these deprotection conditions do not affect oxidizable functionalities including p-methoxybenzyl ethers and alkyl sulfides.
- Madsen, Robert,Roberts, Carmichael,Fraser-Reid, Bert
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p. 7920 - 7926
(2007/10/03)
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- Process for 4-halomethyl-azetidinones by cyclization of O-acylhydroxamates
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A process for 4-halomethylazetidin-2-ones is provided which comprises mixing in an inert solvent a positive halogen reagent in the presence of a weak base with a β,γ-unsaturated O-acylhydroxamate of the formula STR1 wherein R is protected amino, lower alkyl or phenyl substituted lower alkyl, R2 is a substituent such as lower alkyl which may be substituted by formyl, hydroxy, halogen, etc., and R1 is alkoxy, benzyloxy, etc. When R is a protected amino group, the process provides cis-4-halomethylazetidin-2-ones, while when R is alkyl or phenylalkyl, the trans isomer is obtained. The 4-halomethylazetidinones are useful intermediates for known antibiotic compounds.
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- OPTICALLY ACTIVE F-2-ISOPROPOXYPROPIONIC ACID: A NOVEL DERIVATIZING AGENT FOR GAS CHROMATOGRAPHIC ANALYSIS
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F-2-Isopropoxypropionic acid (PIPA) was resolved into enantiomers via its diastereomeric (+)-1-phenylethylamide. (+)-F-2-Isopropoxypropionyl derivatives of several chiral 1-arylalkylamines and α-amino acids were effectively resolved by gas chromatography at low temperature.
- Kawa, Hajimu,Yamaguchi, Fumihiko,Ishikawa, Nobuo
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p. 745 - 748
(2007/10/02)
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- Kinetic Studies in Peptide Chemistry. Coupling, Racemization, and Evaluation of Methods Useful for Shortening Coupling Time
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Kinetic studies were carried out on N-protected methionine and glycylmethionine active esters to determine the racemization rate constants with triethylamine and the coupling rate constants with valine methyl ester.In contrast to cysteine dipeptide active esters, which racemize through an enolization mechanism, the methionine dipeptide active esters racemize through the usual 5(4H)-oxazolone route.The role of sulfur in the side chain is discussed.The time required for coupling a given percentage (e.g., 99 percent) of the amine component can be significantly reduced by using an excess of the active ester.This method is evaluated quantitatively for second-order kinetics.
- Kovacs, J.,Holleran, E. M.,Hui, K. Y.
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p. 1060 - 1065
(2007/10/02)
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