- 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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- Resveratrol amino acid ester derivative and preparation method thereof
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The invention discloses a resveratrol amino acid ester derivative and a preparation method thereof, and belongs to the technical field of fine chemical substance synthesis. The structure of the resveratrol amino acid ester derivative is represented by a formula shown in the description. The resveratrol amino acid ester derivative is synthesized from resveratrol, R amino acid, R' alcohol, dichlorosulfoxide and di(p-nitrobenzene) carbonate with 4-dimethylaminopyridine (DMAP) as a catalyst and acetonitrile as a solvent, wherein the R amino acid is one of alpha-alanine, beta-alanine and gamma-aminobutyric acid, and the R' alcohol is one of methanol, ethanol and n-propanol. The technical problem that resveratrol is difficult to preserve is solved, the pharmacological toxicity introduced by a resveratrol substituent group is lowered, and the resveratrol amino acid ester derivative has the pharmaceutical effects of resveratrol and amino acid. It is expected that the above novel compound playsa great role in beauty treatment and production of fatigue-relieving and blood pressure-lowering medicines.
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Paragraph 0059-0065
(2019/07/04)
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- Synthesis, insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties
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Ryanodine receptors (RyRs) activator has become one class of popular insecticide because of its unique mode of action. In order to find more new RyRs activators as insecticidal agents, a series of 18 novel chiral anthranilic diamides were designed by introducing the D-alanine acid and D-serine acid esters as well as trifluoroethoxyl group into the anthranilic diamide skeleton and synthesized successfully based on anthranilic diamide and FKI-1033 structures. The structures of the title compounds Ia–i and IIa–i were confirmed by melting points, 1H NMR, 13C NMR, elemental analysis and specific optical rotation analysis. The preliminary bioassay results indicated that most of the title compounds exhibited considerable larvicidal activities against oriental armyworm at 10 mg/L, especially Ib, Ie and IIh showed remarkable insecticidal activities at 0.5 mg/L. The larvicidal activity against diamondback moth of Ia and IId were 80% and 90% respectively at 0.0001 mg/L, which was similar to that of chlorantraniliprole. The relationship between structure and insecticidal activity was analyzed to reveal a possible co-regulated effect of the chiral amino acid ester, halogen atom or cyano group, and trifluoroethyloxyl group of the skeleton structures of the title compounds, which will provide useful information for guiding the design and discovery of new RyRs activators and insecticidal agrochemicals.
- Zhou, Shaa,Zhou, Sha,Xie, Yongtao,Meng, Xiangde,Wang, Baolei,Xiong, Lixia,Yang, Na,Li, Zhengming
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supporting information
p. 1254 - 1256
(2017/11/24)
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- Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors
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The simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase-bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.
- Liu, Shuai,Yosief, Hailemichael O.,Dai, Lingling,Huang, He,Dhawan, Gagan,Zhang, Xiaofeng,Muthengi, Alex M.,Roberts, Justin,Buckley, Dennis L.,Perry, Jennifer A.,Wu, Lei,Bradner, James E.,Qi, Jun,Zhang, Wei
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p. 7785 - 7795
(2018/09/13)
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- Imines derived from 4-methyl-4-diphenylphosphorylpentan-2-one and potassium salts of aminocarboxylic acids
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An effective procedure for the preparation of imines based on 4-methyl-4-diphenylphosphorylpentan-2-one, aminoacetic, aminopropionic, and aminobutyric acids with yields of 90–95% was developed. Reaction of dimephosphone (4-methyl-4-dimethoxyphosphorilpent
- Dimukhametov,Mironov,Tatarinov
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p. 882 - 884
(2017/05/29)
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- Chiral phosphorescent probes for amino acids: hybrids of iridium(iii) complexes with synthetic saponite
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An attempt of developing a chiral luminescent probe for amino acids was described. Two types of chiral iridium(iii) complexes were synthesized: [Ir(dfppy)2(R-pep-bpy)]+ (dfppyH = 2-(2′,4′-difluorophenyl)pyridine); R-pep-bpy = 4,4′-bis((R-1,2-dimethylpropyl)aminocarbonyl-2,2′-bipyridine) and [Ir(piq)2(R-pep-bpy)]+ (piqH = 1-phenyisoquinoline). In both complexes, amido groups (R-pep-) were attached to 2,2′-bipyridine with an intension of increasing the affinity for an amino acid. The complexes were optically resolved on a chiral column. When the complexes were adsorbed by the colloidal particles of synthetic saponite, they were highly emissive even in a medium containing water. The remarkable quenching of emission was observed for the combination of [Ir(dfppy)2(R-pep-bpy)]+ and tryptophan methyl ester. By the use of the enantiomeric complexes, the possibility of enantioselective quenching was examined for various amino acid derivatives.
- Sato, Hisako,Tamura, Kenji,Yajima, Tomoko,Sato, Fumi,Yamagishi, Akihiko
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p. 2780 - 2785
(2017/04/03)
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- 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00445
(2017/10/06)
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- Design, synthesis of new chiral fluorine-containing β-hydroxysulfonamides from natural amino acids and study of their anti-inflammatory and analgesic activities
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A series of new chiral fluorine-containing β-hydroxysulfonamides were conveniently synthesized in three steps, starting from natural L-amino acids, and evaluated for their anti-inflammatory and analgesic activities. The structures of these compounds were supported by FT-IR, 1H, 13C and 19F NMR, elemental analysis and HRMS. Among the tested compounds, 4c, 4g and 4h exhibited promising anti-inflammatory activity. Moreover, compound 4h showed a significant analgesic activity. The structure–activity relationships of selected compounds were discussed.
- Gloulou, Monia,Kra?em, Jamil,Jennene, Fay?al,Ghedira, Donia,Amor, Haifa Bel Haj,Lajili, Sirine,Jalleli, Emna,Ferjani, Maha,Bouraoui, Abderrahman,Kallel, Mohamed
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p. 1497 - 1506
(2016/07/06)
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- Synthesis and biological evaluation of novel lipoamino acid derivatives
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Seven novel lipoamino acid conjugates were synthesized from methyl oleate and amino acids. Methyl oleate was grafted to different amino acids using thioglycolic acid as a spacer group. Seven derivatives (3a-g) were prepared and characterized by spectral data (NMR, IR and MS spectral studies). All the derivatives were studied for their antimicrobial, anti-biofilm and anticancer activities. Among all the derivatives, it was found that compound 3b was the most potent antibacterial compound which showed good activity against four Gram positive bacterial strains and also exhibited excellent antifungal activity against a fungal strain. In the anti-biofilm assay, compound 3b showed promising activity with IC50 value of 2.8 μM against Bacillus subtilis MTCC 121. All the compounds showed anticancer activities with 3c showing promising anticancer activity (IC50 = 15.3-22.4 μM) against the four cell lines tested.
- Kaki, Shiva Shanker,Arukali, Sammaiah,Korlipara, Padmaja V.,Prasad,Yedla, Poornachandra,Ganesh Kumar
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supporting information
p. 209 - 212
(2015/12/20)
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- P2X3 AND/OR P2X2/3 COMPOUNDS AND METHODS
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The present application provides novel compounds and methods for preparing and using these compounds. In one embodiment, the compounds are of the structure of formula (I), wherein R1-R4 are defined herein. In a further embodiment, these compounds are useful in method for regulating one or both of the P2X3 or P2X2/3 receptors. In another embodiment, these compounds are useful for treating pain in patients by administering one or more of the compounds to a patient.
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Paragraph 0209; 0210; 0211
(2015/07/07)
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- Crystallographic insight-guided nanoarchitectonics and conductivity modulation of an n-type organic semiconductor through peptide conjugation
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Crystallographic insight-guided nanoarchitectonics of peptide-conjugated naphthalene diimide (NDI) is described. In a bio-inspired approach, non-proteinogenic α-amino isobutyric acid (Aib)- and alanine (Ala)-derived peptides orchestrated the 1D achiral and 2D chiral molecular ordering of NDI, respectively, which resulted in modulation of nanoscale morphology, chiroptical and conductivity properties.
- Pandeeswar,Khare, Harshavardhan,Ramakumar, Suryanarayanarao,Govindaraju
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supporting information
p. 8315 - 8318
(2015/05/13)
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- CARBONITRILE DERIVATIVES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
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The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or -CR0--, where R0 is hydrogen, C1-C6 linear or branched chain alkyl, etc., Z is -CRe --, or, -N--, where Re is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R1 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1-C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1C6 linear or branched chain alkyl, etc.;. R5 and R6 are independently hydrogen or C1-C6 linear or branched chain alkyl, etc.; R8 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1- C6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH2)q--, --(CHRs)q--, or -(CRsRt)q- -, where Rs and Rt are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.
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Page/Page column 148
(2015/12/17)
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- Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): Discovery of 5-((3-fluorophenyl)ethynyl)- N -(3-methyloxetan-3-yl)picolinamide (ML254)
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Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Both allosteric agonism and high glutamate fold-shift have been implicated in the neurotoxic profile of some mGlu5 PAMs; however, these hypotheses remain to be adequately addressed. To develop tool compounds to probe these hypotheses, the structure-activity relationship of allosteric agonism was examined within an acetylenic series of mGlu5 PAMs exhibiting allosteric agonism in addition to positive allosteric modulation (ago-PAMs). PAM 38t, a low glutamate fold-shift allosteric ligand (maximum fold-shift ~3.0), was selected as a potent PAM with no agonism in the in vitro system used for compound characterization and in two native electrophysiological systems using rat hippocampal slices. PAM 38t (ML254) will be useful to probe the relative contribution of cooperativity and allosteric agonism to the adverse effect liability and neurotoxicity associated with this class of mGlu5 PAMs.
- Turlington, Mark,Noetzel, Meredith J.,Chun, Aspen,Zhou, Ya,Gogliotti, Rocco D.,Nguyen, Elizabeth D.,Gregory, Karen J.,Vinson, Paige N.,Rook, Jerri M.,Gogi, Kiran K.,Xiang, Zixiu,Bridges, Thomas M.,Daniels, J. Scott,Jones, Carrie,Niswender, Colleen M.,Meiler, Jens,Jeffrey Conn,Lindsley, Craig W.,Stauffer, Shaun R.
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p. 7976 - 7996
(2013/11/06)
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- Enantioselective synthesis of 1,2,4-triazolines by chiral iron(ii)-complex catalyzed cyclization of α-isocyano esters and azodicarboxylates
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Enantioselective cyclization of α-isocyano esters with azodicarboxylates catalyzed by FeII-N,N′-dioxide complexes has been developed. Under mild conditions, a variety of 1,2,4-triazoline derivatives was obtained in high yields and enantioselectivities.
- Wang, Min,Liu, Xiaohua,He, Peng,Lin, Lili,Feng, Xiaoming
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supporting information
p. 2572 - 2574
(2013/04/10)
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- Controlled drug delivery from mesoporous silica using a pH-response release system
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Mesoporous hollow silica nanoparticles were functionalized with phenanthroline (P-MHS) to prepare a carrier for a host-guest complex. Curcumin was selected as a model drug molecule. The phenanthroline attached to the P-MHS was complexed with Cu2+ through a coordination bond. When the Cu 2+-P-MHS was exposed to ~pH 5, the curcumin was efficiently released into the aqueous phase within 120 min. This work describes a method for functionalizing the surface of the porous silica nanoparticles in a well-defined manner. The P-MHS carrier exhibited controlled release of a model drug under acidic pH conditions.
- Jin, Dalsaem,Lee, Ji Ha,Seo, Moo Lyong,Jaworski, Justyn,Jung, Jong Hwa
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supporting information; experimental part
p. 1616 - 1620
(2012/10/07)
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- Calyxamides A and B, cytotoxic cyclic peptides from the marine sponge Discodermia calyx
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Cyclic peptides containing 5-hydroxytryptophan and thiazole moieties were isolated from the marine sponge Discodermia calyx collected near Shikine-jima Island, Japan. The structures of calyxamides A (1) and B (2), including the absolute configurations of all amino acids, were elucidated by spectroscopic analyses and degradation experiments. The structures are similar to keramamides F and G, previously isolated from Theonella sp. The analysis of the 16S rDNA sequences obtained from the metagenomic DNA of D. calyx revealed the presence of Candidatus Entotheonella sp., an unculturable δ-proteobacterium inhabiting the Theonella genus and implicated in the biosynthesis of bioactive peptides.
- Kimura, Miki,Wakimoto, Toshiyuki,Egami, Yoko,Tan, Karen Co,Ise, Yuji,Abe, Ikuro
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experimental part
p. 290 - 294
(2012/05/05)
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- Sandwich structure of a ruthenium porphyrin and an amino acid hydrazide for probing molecular chirality by circular dichroism
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Owing to the strong Lewis acidity of ruthenium porphyrins, a commercial carbonyl ruthenium porphyrin and an amino acid hydrazide can assemble into a sandwich structure. The nature of such a structure is diagnostic of the absolute configuration of the amino acid by circular dichroism.
- Liang, Qing-Feng,Liu, Juan-Juan,Chen, Jian
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experimental part
p. 3987 - 3991
(2011/08/09)
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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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- 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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- Design and synthesis of N-methylmaleimide indolocarbazole bearing modified 2-acetamino acid moieties as Topoisomerase I inhibitors
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A novel series of N-methylmaleimide indolocarbazole derivatives bearing modified 2-acetamino acid moieties are first reported. The cytotoxic effects of these compounds were tested in five human tumor cell lines. The potent compounds 9a, 9b, 9d, and 9e have been further evaluated for their effect on Topoisomerase I (TOPO I) and cancer cell cycle. It is concluded that the indolocarbazoles with alkyl piperazine or morpholine substituent groups instead of esters or glycosyl residues would have better activities against tumors.
- Li, Zhiyu,Zhai, Fuming,Zhao, Li,Guo, Qinglong,You, Qidong
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scheme or table
p. 406 - 409
(2011/02/26)
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- Phosphorylthioureas and phosphorylureas containing amino acid fragments
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A series of (dialkoxyphosphoryl)thioureas and their 1,3,2-oxazaphosphinane analogs containing fragments of glycine, alanine, ss-alanine, L-aspartic and L-glutamic acids, as well as phosphorylureas derived from glycine and ss-alanine were synthesized in the search for potential biologically active compounds (including possible inhibitors of aspartate trans-carbamoylase).
- Shipov,Genkina,Petrovskii
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p. 2512 - 2516
(2014/05/06)
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- Biomimetic synthesis of esters of natural amino acids
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A method for the synthesis of Gly, Ala, Phe, and Thr esters is proposed and considered as being a stage of possible biomimetic synthesis of peptides. The methyl esters of the said amino acids are obtained via intervention of 2-hydroxypropyl phosphonate. The resulting aminoacyl phosphonates reacts with methanol to produce the amino acid methyl esters, with the release of phosphoric acid. The reaction is carried out at room temperature in water.
- Devedjiev, Ivan T.,Bairyamov, Stanislav G.,Videva, Vladimira S.
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p. 252 - 255
(2008/09/19)
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- A resource-efficient and highly flexible procedure for a three-component synthesis of 2-imidazolines
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(Chemical Equation Presented) A multicomponent reaction between α-acidic isonitriles, primary amines, and carbonyl compounds was studied using 14 different solvents. Depending on the isocyanide that was used, optimal yields for the three-component synthesis of 2H-2-imidazolines were observed in different solvents. The solvents could be used as purchased, and in situ preformation of the imine was not required. By selecting the appropriate solvent, it was possible to considerably expand the range of compatible isocyanides toward less α-acidic isocyanides. Further process simplification was achieved by performing the reaction at higher concentrations and avoiding purification by column chromatography, resulting in a fast, easy to perform, and resource-efficient protocol for this three-component reaction.
- Elders, Niels,Schmitz, Rob F.,De Kanter, Frans J. J.,Ruijter, Eelco,Groen, Marinus B.,Orru, Romano V. A.
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p. 6135 - 6142
(2008/02/10)
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- Methods and compositions for treating amyloid-related diseases
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Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
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Page/Page column 142
(2010/11/24)
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- One pot synthesis of N-acylalanine methyl ester and its uses for the synthesis of oxazole, pyrazole and 1,2,4-triazine derivatives
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THE REACTION of ethyl cyano acetate (3) with alanine methyl ester (2) gave the amide derivative 4. Heterocyclic transformations of the latter product are introduced to form compounds with potential biological and pharmaceutical interest.
- Wardakhan
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p. 325 - 338
(2007/10/03)
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- Quantitative enzymatic protection of D-amino acid methyl esters by exploiting 'relaxed' enantioselectivity of penicillin-G amidase in organic solvent
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A quantitative method for enzymatic protection of esters of various d-amino acids in organic solvent is reported. The lower enantioselectivity displayed by penicillin-G amidase (PGA) from E. coli in organic solvent has been exploited for developing a facile, fast and quantitative method for protection of esters of various d-amino acids via N-acylation. The feasibility of the deprotection of the acylated products was also demonstrated by employing PGA from two different sources in aqueous media. Experimental results are in agreement with previous calculations based on in silico models of the enzyme active site.
- Carboni, Chiara,Quaedflieg, Peter J. L. M.,Broxterman, Quirinus B.,Linda, Paolo,Gardossi, Lucia
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p. 9649 - 9652
(2007/10/03)
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- A novel and facile method to synthesize (R)- and (S)-2-methylpiperazine
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A concise and efficient synthesis of (R)- and (S)-2-methylpiperazine in only five steps from (D)- and (L)-alanine is described. The key step is reaction of benzylamine with a bifunctional molecule to build a six-membered ring.
- Liu, Bo,Xu, Guang-Yu,Yang, Chun-Hao,Wu, Xi-Han,Xie, Yu-Yuan
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p. 4111 - 4118
(2007/10/03)
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- Glutaryl Acylases: One-Reaction Enzymes or Versatile Enantioselective Biocatalysts?
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A significant broad substrate specificity, that crosses over the usual β-lactam derivatives, has been observed with an industrial glutaryl-7-aminocephalosporanic acid acylase (GA). This enzyme possesses significant enantioselective amidase and even esterase activity, with a stereopreference for the S-enantiomer. The easy separation of products from unreacted reagents, possessing different physical-chemical properties, is achieved by solvent extraction, avoiding chromatography or distillation during reaction work-up.
- Raimondi, Stefano,Monti, Daniela,Pagnoni, Ugo Maria,Riva, Sergio
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p. 783 - 789
(2007/10/03)
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- Peptides: Part II1 -prop-2-ynyltriphenylphosphonium bromide as coupling agent for peptide synthesis
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Prop-2-ynyltriphenylphosphonium bromide has been used as a coupling agent for peptide synthesis. Seven dipeptides and a tripeptide have been prepared.
- Ali,Roy,Zaman,Islam,Haque
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p. 769 - 772
(2007/10/03)
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- Substituent effect on acidity of substituted 2-(4-nitrobenzoylamino)alkanamidesin methanol-dimethyl sulfoxide mixtures
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The dissociation constants of substituted 2-(4-nitrobenzoylamino)alkanamides, N-[2-(4-nitrobenzoylamino)aikanoyl]pyrrolidines, and N-alkyl-4-nitrobenzamides have been measured spectrophotometrically in 60 and 80% v/v DMSO. The pKA values of these N-acids are discussed from the point of view of substituents at the acetamide a-carbon atom.
- Mitas, Petr,Sedlak, Milos,Kavalek, Jaromir
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- (S)-form of α-methyl-N(α)-phthalimidoglutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-α production by human leukemia cell HL-60: implication of optical resolution of thalidomidal effects
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The rate of racemization of N(α)-phthalimidoglutarimide (thalidomide) was determined as its half life to be 566 min at pH 7.4/37°C. This fast racemization of thalidomide resulted in no apparent difference between (S)- and (R)-forms of the compound on enhancing activity of phorbol ester-induced tumor necrosis factor (TNF)-α production by human leukemia HL-60 cells. Optically pure forms of structurally related analog of thalidomide, (S)- and (R)-α-methyl-N(α)-phthalimidoglutarimides, (methylthalidomides), which do not racemize under the physiological condition, were prepared. Only (S)-form of methylthalidomide, but not its (R)-form, elicited TNF-α production- enhancing effect, suggesting that the (S)-isomer of thalidomide would be the active form in terms of thalidomidal biological response modifying effects.
- Nishimura,Hashimoto,Iwasaki
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p. 1157 - 1159
(2007/10/02)
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- (3R)- AND (3S)-METHYLPIPERAZINE-2,5-DIONE DERIVATIVES AS USEFUL INTERMEDIATES IN THE ENANTIOSELECTIVE SYNTHESIS OF α-AMINO ESTERS
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Treatment of (3S)-3-methylpiperazine-2,5-dione 1 with lithium hexamethyldisilazide (LHMDS) followed by alkylation with several alkyl bromides affords (3S,6S)-3-methyl-6-alkyl derivatives 3 (a-e) in d.e. greater than 98percent.The same reaction sequence carried out on the (3R)-derivative 2 leads to a diastereoisomeric mixture of (3R,6S)-4 (a-e) and (3R,6R)-5 (a-e), the ratio 5 : 4 depending on the alkylating reagent.The configuration at C-6 (of 3, 4 and 5) has been assigned on the basis of 1H-NMR spectroscopic data and conformational analysis performed by the MMPMI program.Cleavage of the heterocyclic ring of 3 (b, d) and 5 (b, d) leads to the corresponding (S)- and (R)-α-amino esters respectively.
- Orena, Mario,Porzi, Gianni,Sandri, Sergio
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p. 2125 - 2152
(2007/10/02)
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- Potential application of Sulfolobus solfataricus as catalyst in organic synthesis
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Sulfolobus solfataricus, a thermoacidophilic archaeon, has been utilized as catalyst for several enzymatic transformations such as carbonyl-alcohol oxidoreductions, synthesis of glycosides, kinetic resolution of aminoacid esters, etc.All these reactions have been carried out at 75 deg C in accordance with the thermophilic nature of the enzymes present in the organisms.
- Trincone, Antonio,Nicolaus, Barbara,Lama, Licia,Gambacorta, Agata
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- Preferential Formation of Amino Acid Esters in Aqueous Alcohol Solutions: Solvolysis of 6,6'-Bis(aminoacylamino)-2,2'-bipyridine by Metal Coordination
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Exclusive formation of amino acid esters took place at an appreciable rate in the CuII-catalysed solvolysis of 6,6'-(α-alanylamino or α-phenylalanylamino)-2,2'-bipyridine in alcohol-borate buffer (pH 7.2) solutions at 20 deg C via formation of an amide-O-coordinated complex, even though appreciable amounts of water (0-40percent v/v) were present in the solution.
- Araki, Koji,Kuboki, Takashi,Yamada, Masaki,Shiraishi, Shinsaku
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p. 1060 - 1062
(2007/10/02)
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- Preparation of (R)-2-azidoesters from 2-((p-nitrobenzene)sulfonyl)oxy esters and their use as protected amino acid equivalents for the synthesis of di- and tripeptides containing D-amino acid constituents
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(R)-2-Azidoesters and their derived (R)-2-azido acids are readily prepared from common amino acids by an inversion methodology that employs (S)-2-nosyloxyesters as key intermediates. The (R)-2-azidoesters can be used as protected amino acid equivalents in peptide synthesis. Basic hydrolysis frees the carboxyl group. Triphenylphosphine/water is used to free the amine group. By these reactions a variety of L-D and D-L dipeptides, L-D-L tripeptides, and depsipeptides can be prepared easily in good yields, and without detectable epimerization.
- Hoffman,Kim
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p. 3007 - 3020
(2007/10/02)
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- Electrosynthesis of Amino Acids from a Molybdenum Nitride via Nitrogen-Carbon and Carbon-Carbon Bond Formation Reactions involving Imides and Nitrogen Ylides: X-Ray Structure of trans-*CH2Cl2
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Sequential nitrogen-carbon and carbon-carbon bond formation, and an electrochemical Mo-N bond cleavage step, define a pathway to methyl esters of the amino acids glycine and alanine from the molybdenum nitride trans-, a key intermediate being the metallo-nitrogen ylide trans-, the structure of which has been determined crystallographically.
- Hughes, David L.,Ibrahim, Saad K.,Macdonald, Colin J.,Ali, Hapipah Mohd.,Pickett, Christopher J.
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p. 1762 - 1763
(2007/10/02)
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- Optical Resolution of Amino Acid and Hydroxycarboxylic Acid Esters by Complexation with Optically Active Host Compounds: a Crystallographic Result
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Selected esters derived from amino and hydroxycarboxylic acids have been resolved by inclusion complexation with optically active host compounds derived from tartaric acid.The crystal structure of the inclusion compound I (R,R)-(-)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4-dioxaspirononane-*1/2(methyl 3-hydroxybutanoate) is reported.I is monoclinic P21, a = 9.176(2), b = 39.70(2), c = 9.216(2) Angstroem, β = 119.45(1) deg, V = 2923(2) Angstroem3.The structure was solved by direct methods and refined to a final R value of 0.037.Host and guest molecules are linked by hydrogen bonding.
- Toda, Fumio,Sato, Atsushi,Nassimbeni, Luigi R.,Niven, Margaret L.
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p. 1971 - 1976
(2007/10/02)
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- A New Method for the α-Vinylation of Protected α-Amino Acids; Ethylene Oxide as Vinyl Cation Equivalent
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A convenient and conceptually new strategy for the transformation of α-amino acids into the corresponding α-vinyl amino acids is described; commercially available ethylene oxide serves as a vinyl cation equivalent.
- Berkowitz, David B.
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p. 1819 - 1829
(2007/10/02)
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- Nucleophilic Substitution Reactions of Alkyl Halides By Using New Polymer-Supported Reagents Containing Hemin
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A new polymer reagent consisting of hemin, divinylbenzene, and 2-methyl-5-vinylpyridine was synthesized by suspension copolymerization.Substitution reactions of primary, secondary, and tertiary alkyl halides with the hemin copolymer combined with cyanide, azide, and thiocyanate ions were given satisfactory yields.This reaction mechanism was revealed to be a SNi type on the basis of stereochemical study.The hemin copolymer was not only a polymer-supported reagent with functional capabilities, but also served to separate the product from the reaction mixture.
- Saito, Kiyoshi,Harada, Kaoru
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p. 2562 - 2566
(2007/10/02)
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- ENANTIOSELECTIVE ELECTROPHILIC BOND CONSTRUCTION TO THE α-CARBON OF α-AMINOACIDS
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In this report, we describe three possibilities for aminoacid synthesis using an enantioselective electrophilic process.Thus, enantioselective carboxylation, alkylation and protonation of Schiff bases yield optically active aminoacids with e.e. up to 76percent.
- Duhamel, Lucette,Duhamel, Pierre,Fouquay, Stephane,Eddine, Jamal Jamal,Peschard, Olivier,et al.
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p. 5495 - 5506
(2007/10/02)
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- Alkylation and Condensation Reactions of N,N-Dibenzylglycine Esters: Synthesis of α-Amino Acid Derivatives
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Upon deprotonation N,N-dibenzylglycine esters undergo alkylation and condensation reactions at the α-carbon atom with various electrophiles.
- Gray, Brian D.,Jeffs, Peter W.
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p. 1329 - 1330
(2007/10/02)
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- A Facile Synthesis of α-Amino Esters via Reduction of α-Nitro Esters Using Ammonium Formate as a Catalytic Hydrogen Transfer Agent
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Various nitroesters 3 were selectively and rapidly reduced to their corresponding amino esters 4 in very good yield using anhydrous ammonium formate as a catalytic hydrogen transfer agent.
- Ram, Siya,Ehrenkaufer, Richard E.
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p. 133 - 135
(2007/10/02)
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- Reaction of Ketene Silyl Acetals with Diazonium Salts: a Novel α-Amino Acid Ester Synthesis
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The reaction of ketene silyl acetals with arenediazonium tetrafluoroborate gave α-hydrazono and α-azo esters, which were easily hydrogenated to α-amino esters.
- Sakakura, Toshiyasu,Tanaka, Masato
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p. 1309 - 1310
(2007/10/02)
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- ENANTIOSELECTIVE SYNTHESIS OF NON-PROTEINOGENIC AMINO ACIDS VIA METALLATED BIS-LACTIM ETHERS OF 2,5-DIKETOPIPERAZINES
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Bis-lactim ethers 1 of 2,5-diketopiperazines contain a chiral inducing center, an acidic CH-bond and two sites susceptible to hydrolysis.They react with BuLi to give Li compounds of type 4, 15, 29 or 32, which possess a prochiral C atom.They readily add electrophiles (such as alkylating agents or carbonyl compounds) with unusually high diastereoface differentiation.In many cases the d.e-value (d.e. = diastereomeric excess = asymmetric induction) of the adduct exceeds 95percent.On hydrolysis the adducts are cleaved liberating the chiral auxiliary (used to build up the bis-lactim ether 1) and the target molecules, the optically active amino acid methyl esters of type 8, 19, 25 or 36.The two amino acid esters are separable either by fractional distillation or (eventually after further hydrolysis to amino acids) by chromatography.Transition state models are discussed that could explain the exceptionally high asymmetric induction and the predictability of the induced configuration.
- Schoellkopf, Ulrich
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p. 2085 - 2092
(2007/10/02)
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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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- Flow 1H nmr study of the rapdid nucleophilic addition of amino acids to 4-formylpyridine
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Rapid addition of primary amino acids and imidazole to 4-formylpyridine to form carbinolamine intermediates in water has been studied by means of stopped-flow 1H nuclear magnetic resonance spectroscopy.The equilibrium constant Kn for this process was determined using stopped-flow uv spectroscopy.For the amino acid D,L-alanine and its derivatives , D,L-alanine methyl ester and D,L-alanylglycine Kn does not appear to correlate with Ka, the acid dissociation constant.Values of kn, the addition rate constant, appear to be independent of pH and bufferconcentration fo these nucleophiles.The limited data indicate that the variation in rates of nucleophilic addition to 4-formylpyridine cannot be accounted for in terms of pKa, Kn or related to systematic changes in structure of the nucleophile.As a group, the primary amino acid D,L-alanine and its derivatives have comparable kn values within a factor of two in spite of their different pKa values.Imidazole, an aromatic secondary diamine, has a kn value that is 10 to 20 times larger than these primary amines and has a relatively small Kn value.At the same time , its kn value is comparable to that found previously for sarcosine, a secondary acyclic amino acid having substantially larger pKa and Kn values.The nucleophilic addition step of primary amino acid and derivatives is rapid relative to the subsequent dehydration and prototropic shift steps.It occurs in a pH range at which pyridine nitrogen protonation is negligible.
- Tan, Liang K.,Cocivera, Michael
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p. 772 - 777
(2007/10/02)
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