- Characterization of binding affinities in a chromatographic system by suspended state HR/MAS NMR spectroscopy
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In the current work a racemate of (R)-and (S)-benzylmandelate was separated with a stereoselective polysaccharide-based chiral stationary phase by HPLC. To elucidate the occurring chiral molecular recognition processes in the heterogeneous system used, NMR spectroscopy was chosen under high resolution/magic angle spinning (HR/MAS) NMR conditions in the suspended state. Therefore, and as a proof of concept, a combination of several NMR methods such as spin - lattice relaxation time (T1) measurements (T1), the saturation transfer difference, and the 2D experiment of the transferred nuclear overhauser enhancement spectroscopy technique were applied. With HR/MAS NMR it is feasible to combine NMR and chromatography to achieve further insights into the separation process. Copyright
- Friebolin, Volker,Marten, Silvia,Albert, Klaus
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Read Online
- Selective Monovalent Galectin-8 Ligands Based on 3-Lactoylgalactoside
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Galectin-8 has gained attention as a potential new pharmacological target for the treatment of various diseases, including cancer, inflammation, and disorders associated with bone mass reduction. To that end, new molecular probes are needed in order to better understand its role and its functions. Herein we aimed to improve the affinity and target selectivity of a recently published galectin-8 ligand, 3-O-[1-carboxyethyl]-β-d-galactopyranoside, by introducing modifications at positions 1 and 3 of the galactose. Affinity data measured by fluorescence polarization show that the most potent compound reached a KD of 12 μM. Furthermore, reasonable selectivity versus other galectins was achieved, making the highlighted compound a promising lead for the development of new selective and potent ligands for galectin-8 as molecular probes to examine the protein's role in cell-based and in vivo studies.
- Anderluh, Marko,Girardi, Benedetta,Leffler, Hakon,Manna, Martina,Mravljak, Janez,Nilsson, Ulf J.,Ricklin, Daniel,Schwardt, Oliver,Van Klaveren, Sjors,Jakopin, ?iga,Toma?i?, Tihomir
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supporting information
(2021/10/08)
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- ENDOPARASITIC DEPSIPEPTIDES
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The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof (1) wherein each of R1, R2, R3, R4, L1, and L2, are as defined herein. The present invention also contemplates compositions and methods of treatment as an endoparasiticide with a Formula (1) compound.
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Page/Page column 56; 59; 60
(2019/06/17)
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- ENDOPARASITIC DEPSIPEPTIDES
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The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof wherein each of R1, R2, R3, R4, L1, and L2 are as defined herein. The present invention also contemplates compositions, methods of treatment, and uses as a medicament to treat an animal for an endoparasitic infection with a Formula (1 ) compound.
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Page/Page column 44; 48
(2019/11/28)
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- Learning from Peptides to Access Functional Precision Polymer Sequences
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Functional precision polymers based on monodisperse oligo(N-substituted acrylamide)s and oligo(2-substituted-α-hydroxy acid)s have been synthesized. The discrete sequences originate from a direct translation of side-chain functionality sequences of a peptide with well-studied properties. The peptide was previously selected to solubilize the photosensitizer meta-tetra(hydroxyphenyl)chlorin. The resulting peptidomimetic formulation additives preserve the drug solubilization and release characteristics of the parent peptide. In some cases, superior properties are obtained, reaching up to 40 % higher payloads and 27-times faster initial drug release.
- Maron, Eva,Swisher, Jordan H.,Haven, Joris J.,Meyer, Tara Y.,Junkers, Tanja,B?rner, Hans G.
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supporting information
p. 10747 - 10751
(2019/07/09)
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- Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation inhibitor
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The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation-elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine moiety. The final step involved execution of a key macrolactamization reaction between the hindered unnatural N,O-dimethylthreonine and ?2-hydroxyleucine residues.
- Kaur, Harveen,Harris, Paul W. R.,Little, Peter J.,Brimble, Margaret A.
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supporting information
p. 492 - 495
(2015/03/05)
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- Organocatalytic synthesis of optically active aryllactic acid derivatives from β-ketosulfoxides
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The organocatalytic synthesis of new α-acyloxy-3-arylpropionic thioesters has been accomplished providing some enantioenriched important aryllactic acid derivatives in good yield and enantioselectivities.
- Capitta, Francesca,Melis, Nicola,Secci, Francesco,Romanazzi, Giuseppe,Frongia, Angelo
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p. 649 - 660
(2015/10/19)
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- Preparation and evaluation at the delta opioid receptor of a series of linear Leu-enkephalin analogues obtained by systematic replacement of the amides
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Leu-enkephalin analogues, in which the amide bonds were sequentially and systematically replaced either by ester or N-methyl amide bonds, were prepared using classical organic chemistry as well as solid phase peptide synthesis (SPPS). The peptidomimetics were characterized using competition binding, ERK1/2 phosphorylation, receptor internalization, and contractility assays to evaluate their pharmacological profile over the delta opioid receptor (DOPr). The lipophilicity (LogD7.4) and plasma stability of the active analogues were also measured. Our results revealed that the last amide bond can be successfully replaced by either an ester or an N-methyl amide bond without significantly decreasing the biological activity of the corresponding analogues when compared to Leu-enkephalin. The peptidomimetics with an N-methyl amide function between residues Phe and Leu were found to be more lipophilic and more stable than Leu-enkephalin. Findings from the present study further revealed that the hydrogen-bond donor properties of the fourth amide of Leu-enkephalin are not important for its biological activity on DOPr. Our results show that the systematic replacement of amide bonds by isosteric functions represents an efficient way to design and synthesize novel peptide analogues with enhanced stability. Our findings further suggest that such a strategy can also be useful to study the biological roles of amide bonds.
- Rochon, Kristina,Proteau-Gagne, Arnaud,Bourassa, Philippe,Nadon, Jean-Francois,Coite, Jerome,Bournival, Veronique,Gobeil, Fernand,Guerin, Brigitte,Dory, Yves L.,Gendron, Louis
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p. 1204 - 1216
(2013/09/23)
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- Continuous multiple liquid-liquid separation: Diazotization of amino acids in flow
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A second-generation laboratory-scale, modular liquid-liquid separation device based on computer-controlled high-pressure pumps and a high-resolution digital camera has been invented. The diazotization of amino acids to produce valuable chiral hydroxyacids is demonstrated in flow for the first time. The use of a triple-separator system in conjuction with the developed diazotization process allows the safe and efficient production and automated isolation of multigram quantities of valuable chiral hydroxyacids.
- Hu, Dennis X.,O'Brien, Matthew,Ley, Steven V.
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supporting information; experimental part
p. 4246 - 4249
(2012/10/08)
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- Synthesis, characterization and activity of new phosphonate dipeptides as potential inhibitors of VanX
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VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of seven phosphonate dipeptide analogs of D-ala-D-ala with various substituent, the activity evaluation indicated that six of these phosphonate analogs inhibit VanX with IC50 of 0.48-8.21 mM. These data revealed a structure-activity relationship which is that the large substituent group on β-carbon resulted in low binding affinity of the phonphonate analog to VanX. This information will be helpful to guide the design and synthesis of the tightly-binding inhibitors for VanX.
- Jia, Chao,Yang, Ke-Wu,Liu, Cheng-Cheng,Feng, Lei,Xiao, Jian-Min,Zhou, Li-Sheng,Zhang, Yi-Lin
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p. 482 - 484
(2012/03/11)
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- Solution-phase peptide synthesis; Synthesis of 'North-Western' and 'South Eastern' fragments of the antifungal cyclodepsipeptide petriellin A
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The solution-phase synthesis of two highly modified peptides, a hexamer and a heptamer, that constitute the two halves of the antifungal cyclic depsipeptide, Petriellin A, is reported. CSIRO 2008.
- Aurelio, Luigi,Brownlee, Robert T. C.,Hughes, Andrew B.
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p. 615 - 629
(2008/12/22)
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- Total synthesis of hirsutellide A
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The total synthesis of hirsutellide A 1 was described. The linear hexadepsipeptide precursor 2 was synthesized in 45% yield from N-Boc-Me-Gly by three coupling reactions with DCC, HATU and BOP-Cl, respectively. Macrocyclization was successfully performed on the fully deprotected amino acid 14 with BOP-Cl in 15% yield and with FDDP in 22% yield.
- Xu, Yanjie,Chen, Ligong,Duan, Xuemin,Meng, Yi,Jiang, Liqin,Li, Meiling,Zhao, Guangle,Li, Yang
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p. 4377 - 4379
(2007/10/03)
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- Synthesis of the key precursor of Hirsutellide A
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Hexadepsipeptide 2, the precursor of Hirsutellide A (1), was synthesized in an overall yield of 45% from N-Boc-Me-Gly via three coupling reactions using dicyclohexylcarbodiimide (DCC), O-(7-azabenzotriazol-1-yl)-N,N,N′, N′-tetramethyluronium hexafluorophosphate (HATU) and bis(2-oxo-3- oxazolidinyl)phosphinic chloride (BOP-Cl), respectively.
- Xu, Yanjie,Duan, Xuemin,Li, Meiling,Jiang, Liqin,Zhao, Guangle,Meng, Yi,Chen, Ligong
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p. 259 - 264
(2007/10/03)
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- Synthesis of brassinosteroids of varying acyl side chains and evaluation of their brassinolide-like activity
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Brassinosteroids containing various side chain moieties were synthesized and their activity was determined as the reciprocal logarithm of the ED 50 (50% effective dose per plant in moles) in the rice lamina inclination assay using synergist indole-3-acetic acid (IAA). The introduction of a hydroxyl group in the α-position to the carbonyl group of the ester structure significantly enhanced the activity. 2α,3α-Dihydroxy- 17β-[(2R,3S)-2-hydroxy-3-methylpentanoyl]oxy-B-homo-7-oxa-5α- androstan-6-one showed the highest activity, for which the pED50 was determined to be 10.5 under synergistic conditions with IAA. Under identical conditions, the pED50 values of brassinolide and castasterone were determined to be 13.6 and 12.3 respectively. With respect to the α-carbon of the acyl moiety, the R-form was 10 times more potent than the corresponding S-form. Substituting the terminal structure (Et) of the side chain to that of the most potent compound, brassinolide (i-Pr), did not increase the activity.
- Uesusuki, Shinya,Watanabe, Bunta,Yamamoto, Shuji,Otsuki, Junko,Nakagawa, Yoshiaki,Miyagawa, Hisashi
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p. 1097 - 1105
(2007/10/03)
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- Expanding the utility of proteases in synthesis: Broadening the substrate acceptance in non-coded amide bond formation using chemically modified mutants of subtilisin
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The strategy of combined site directed mutagenesis and chemical modification creates chemically modified mutants (CMMs) with greatly broadened substrate specificities. We have previously reported that the CMMs of subtilisin Bacillus lentus (SBL) are efficient catalysts for the coupling of both L- and D-amino acids. We now report that these powerful catalysts also allow amide bond formation between a variety of non-coded carboxylic acids, including β-alanine and β-amino homologues of phenylalanine, with both L- and D-amino acid nucleophiles. As a guide to enzyme efficiency, a hydrolysis assay indicating pH change has been employed. CMMs selected by this screen furnished higher yields of coupling products compared to the wild-type enzyme (WT). Furthermore, both WT and CMM enzymes allow highly stereoselective aminolysis of a meso diester with an amino acid amine. These results highlight the utility of CMMs in the efficient formation of non-coded amides as potential peptide isosteres.
- Khumtaveeporn, Kanjai,Ullmann, Astrid,Matsumoto, Kazutsugu,Davis, Benjamin G.,Jones
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p. 249 - 261
(2007/10/03)
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- Improved Cs2CO3 promoted O-alkylation of acids
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Cesium carbonate mediated O-alkylation of carboxylic acids was efficiently carried out under mild in situ conditions to give the corresponding esters exclusively. Chiral templates including α-hydroxy and α-alkoxy acids were also converted to their corresponding esters with no observed racemization.
- Parrish, Jay P.,Dueno, Eric E.,Kim, Seok-In,Jung, Kyung Woon
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p. 2687 - 2700
(2007/10/03)
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- Design of mechanism-based carboxypeptidase A inactivators on the basis of the X-ray crystal structure and catalytic reaction pathway
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The X-ray crystal structure of the complex of carboxypeptidase A (CPA) and Gly-Tyr, has been documented. The crystal structure reveals that both the amide carbonyl oxygen and the terminal amino nitrogen of Gly-Tyr coordinate to the active site zinc ion of CPA in a bidentate fashion, whereby the zinc-bound water molecule is displaced by the amino group. As to the catalytic mechanism of CPA, it is generally believed that while in the cases of ester substrates the carboxylate of Glu-270 functions as the nucleophile which attacks the scissile carbonyl carbon (anhydride pathway), in the case of peptide substrates the zinc-bound water molecule attacks the scissile peptide bond (general base pathway). In light of the X-ray crystal structure and the proposed catalytic mechanism for the enzyme, it is envisioned that the ester bond of O-(hydroxyacetyl)-l-β-phenyllactic acid (l-1) would be hydrolyzed by the attack of the carboxylate of Glu-270 to generate an anhydride intermediate. The latter intermediate would then undergo an intramolecular rearrangement initiated by the attack of the hydroxyl to result in to form an ester bond with the Glu-270 carboxylate. This ester formation impairs the catalytic activity of CPA. We have demonstrated using kinetic analysis that l-1 is indeed an inactivator for the enzyme having the k(inact)/K(I) value of 0.057M-1s-1. We have also demonstrated that N-(hydroxyacetyl)-l-phenylalanine (l-2) inactivates the enzyme with the k(inact)/K(I) value of 0.071M-1s-1, suggesting that the carboxylate becomes to attack the peptide carbonyl carbon to generate the same anhydride intermediate as that formed in the inactivation of CPA by l-1. The formation of the anhydride intermediate rather than a tetrahedral transition state that is expected for peptide type substrates was envisioned to occur on the ground that the zinc-bound water molecule is displaced by the hydroxyl of l-2 upon binding to the enzyme. Copyright (C) 1998 Elsevier Science Ltd.
- Lee, Kyung Joo,Kim, Dong H.
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p. 1613 - 1622
(2007/10/03)
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- Stereoselective Pseudomonas cepacia lipase mediated synthesis of α-hydroxyamides
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A new method for the synthesis of α-hydroxyamides via the Pseudomonas cepacia lipase catalyzed amidation of α-hydroxyesters in non-aqueous media is described. Reactivities of α-hydroxy benzyl esters are excellent, resulting in rapid conversions to good yields of α-hydroxyamides, while ethyl and methyl esters react more slowly, and some hindered esters show no reactivity under the conditions studied. Some benzyl esters react stereoselectively, producing excellent yields of asymmetric α-hydroxyamides.
- Adamczyk, Maciej,Grote, Jonathan,Rege, Sushil
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p. 2509 - 2512
(2007/10/03)
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- Building Units for N-Backbone Cyclic Peptides. 3. Synthesis of Protected Nα-(ω-Aminoalkyl)amino Acids and Nα-(ω-Carboxyalkyl)amino Acids
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An improved synthesis of a family of amino acids that contain ω-aminoalkyl groups and of a new family containing ω-carboxyalkyl groups linked to the α-amine is described. The synthesis was performed by alkylation of suitably monoprotected alkylenediamines and protected ω-amino acids with triflates of α-hydroxy acid esters. The reaction proceeded with inversion of configuration yielding optically pure products. The Nα-(ω-aminoalkyl)amino acids and Nα-(ω-carboxyalkyl)amino acids were orthogonally protected to allow their incorporation into peptides by solid-phase peptide synthesis (SPPS) methodology.
- Muller, Dan,Zeltser, Irena,Bitan, Gal,Gilon, Chaim
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p. 411 - 416
(2007/10/03)
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- Synthesis of α-aminophosphonic octapeptide, Phe-Gly-Ser-Leu-Ala(P)-Phl-Leu-Pro, an analog with partial sequence of erb B-2 gene product
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A chemical synthesis was performed of an octapeptide with a phosphonic ester linkage, which corresponds to a variation of the partial sequence of a gene product of erb B-2. The phosphonic ester linkage was successfully prepared through a coupling reaction
- Inami,Teshima,Miyashita,Shiba
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p. 942 - 949
(2007/10/02)
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- A model reaction for assessing the coupling and chiral efficiency of reagents in depside bond formation
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The formation of Fmoc-L-Ala-L-Phlac-OBzl (and Fmoc-D-Ala-L-Phlac-OBzl if there is racemisation) has been monitored by HPLC analysis for a number of coupling conditions between Fmoc-L-Ala-OH and H-Phlac-OBzl.For this depside link formation it is revealed that CDI, DCC/DMAP and mixed anhydride couplings gave yields near to 50percent.Couplings via TBTU, TNTU and TSTU gave lover yields.The best yields were achieved by acid chloride (61percent) urethane-N-carboxyanhydrides (80percent) and by PyBroP coupling (82percent).
- Davies, John S.,Howe, Joanne,Breton, Murielle Le
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p. 2335 - 2340
(2007/10/03)
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- Total Synthesis of the Anthelmintic Cyclodepsipeptide, PF1022A
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The anthelmintic cyclooctadepsipeptide PF1022A and its antipode were synthesized starting from L-Nα-Boc-leucine (for PF1022A), D-N4a-Boc-leucine (for the antipode), L-lactic acid, and L-phenyllactic acid using Mitsunobu reaction and/
- Ohyama, Makoto,Iinuma, Katsuharu,Isogai, Akira,Suzuki, Akinori
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p. 1193 - 1194
(2007/10/02)
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- Synthesis of (15)N-Labelled Chiral Boc-Amino Acids from Triflates: Enantiomers of Leucine and Phenylalanine
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An efficient synthesis of (15)N-labelled chiral Boc-amino acids by triflate alkylation of di-tert-butyl iminodicarbonate is reported.Both enantiomers of Boc-Leucine and -phenylalanine were synthesized from commercial α-amino acids of opposite configuration via α-hydroxy carboxylic acids provided by diazotization, thus extending the scope of an earlier exploratory study.The high chiral purity of the final products was confirmed by HPLC.These labelled amino acid derivatives are suitable for direct application to the synthesis of labelled peptides.
- Degerbeck, Fredrik,Fransson, Bengt,Grehn, Leif,Ragnarsson, Ulf
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- HYDROXYAZIDO DERIVATIVES AND RELATED COMPOUNDS AS RENIN INHIBITORS
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Novel compounds useful as renin inhibitors are provided. The compounds are hydroxyazido derivatives having the structural formula STR1 wherein the substituents R 1 through R 7 are as defined herein. Analogs of these compounds which are ketozaido derivatives are also provided. Additionally disclosed re methods for using the novel compounds to treat hypertension, and pharmaceutical compositions containing the compounds. Of particular interest are formulations for oral administration.
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- Raman spectral evidence for an anhydride intermediate in the the catalysis of ester hydrolysis by carboxypeptidase A
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Single crystal of carboxypeptide A, grown at pH 7.5, have been soaked with solutions of a chromophric substrate, the ester of p-dimethulaminobenzoic acid and L-β-phenyllactic acid, at pH = 8. The enzyme in crystals catalyzes the conversion of the ester to the acid and alcohol products. During this process, pre-resonance-enchanced Raman spectra of the interior of the crystal were a taken using a laser Raman microscope. In addition to the Raman bands characteristic to the substrate and the acid product, weak but reproducible bands are observed in the frequency region of 1700-1800 cm1. Band in this region are unique to organic acid anhydrides and indicate the accumulation of an anhydride intermediate during catalysis. A comparison of these spectra with of those of model componds designed to mimic a pure anhydrida intermediate and a Zn(II)-complexed anhydride intermediate suggests the active-site Zn(II) is sometimes bound to the carbonyls of the anhydride intermediate. In an attempt to observe the intermediate in the reverse reaction, the hydrolysis products of the ester substrate were combined with the enzyme crystal, and Raman spectra were obtained from the interior of the crystal. Since the the Raman spectrum taken during the forward reaction is dominated by the presence of the excess subtrate while thr Raman spectrum taken during the reverse reaction contains no substrate bands, the two are quite different. However, there are Raman bands in the spectrum taken during the reverse direction that correlate well with the bands produced from the forward reaction and with the bands of the model compounds that are assigned to the anhydride intermediate. This indicates as that the reverse reaction proceeds as far as the formation of the intermediate, but no mesaureable substrate is formed. Since carbonyle frequencies versus are very sensitive to the molecular environment, the carbonyl frequencies of the easter substrate, parotonated acid product, and mixed anhydride model compounds were measured in various solvents. Plots were made of the carbonyl frequencies versus Gutmann's electron acceptor numbers of the solvents. It is shown that only the mixed anhydride can posses carbonyl frequencies in the region 1720-1800 cm-1. This appears to rule out the possibility that the bands odserved from th enzyme/ligans spectra are to attributable to easter substrate or acid product. These data are consistent with a mechanism that involves a mixed anhydride intermediate that becomes activated toward hydrolysis through binding of one or both cabonyls to the active-site Zn(II).
- Britt, B. Mark,Peticolas, Warner L.
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p. 5295 - 5303
(2007/10/02)
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- N-HETEROCYCLIC ALCOHOL DERIVATIVES
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Compounds of the formula STR1 wherein R 1 is an N-heterocyclic group as defined herein, are disclosed. These compounds are inhibitors of renin and therefore useful as cardiovascular agents.
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- Novel amino acid derivatives possessing renin-inhibitory activities
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An amino acid derivative of the general formula: wherein, R1? is a lower alkyl group and R11 is (wherein R111 is a lower alkyl group and n is an integer of 1 to 5) or a lower alkyl group which may be substituted by hydroxy group or methoxyethoxymethoxy group, or R1? and R11 are combinedly together with the adjacent nitrogen atom; R12 is a hydrogen atom, CnH2n+ 1-O-CO-(n is as defined above) or R13 is a lower alkyl group which may be substituted by substituent(s) selected from HOOC-(H?C)n-O-, R12-NH-(n and R12 are as defined above) and pyridyl group; X is-CH?-,-O-or-NH-and Y is-O-or-NH-; wherein (wherein Z is-O-,-S-,-S(O)-,-S(O)?-,-CH?-,-CH(OH)-,---,-NH-or and a and b are independently an integer of 1 to 4 and the total of a and b is not more than 5) ; R2 is an aralkyl group which may be substituted by lower alkyl group(s); R3 is a hydrogen atom or a lower alkyl group; R? is a lower alkyl group; and A is hydroxy group and B is a hydrogen atom, or A and B are carbonyl group combinedly together with the adjacent carbon atom, a pharmaceutically acceptable acid addition salt or an ester thereof is described. The compounds of the invention possess inhibitory activities against renin and are useful as an antihypertensive agent.
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- Synthesis and biological activity of some transition-state inhibitors of human renin
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A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu-(OH)-Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (Cha-(OH)-Val) was prepared.
- Buhlmayer,Caselli,Fuhrer,Goschke,Rasetti,Rueger,Stanton,Criscione,Wood
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p. 1839 - 1846
(2007/10/02)
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- NOVEL 5-AMINO-4-HYDROXYVALERYL DERIVATIVES
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Compounds of the formula STR1 in which R 1 represents hydrogen or acyl, A represents an optionally N-alkylated α-amino acid residue which is bonded N-terminally to R 1 and C-terminally to the group--NR 2--, R 2 represents hydrogen or lower alkyl, R 3 represents hydrogen, lower alkyl, optionally etherified or esterified hydroxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl-lower alkyl, tricycloalkyl-lower alkyl, aryl or aryl-lower alkyl, R 4 represents hydroxy or etherified or esterified hydroxy, R 5 represents lower alkyl having 2 or more carbon atoms, optionally etherified or esterified hydroxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, tricycloalkyl, tricycloalkyl-lower alkyl, aryl, aryl-lower alkyl, optionally substituted carbamoyl, optionally substituted amino, optionally substituted hydroxy or optionally substituted mercapto and R 6 represents substituted amino, and salts of such compounds having salt-forming groups inhibit the blood pressure-increasing action of the enzyme renin and can be used as antihypertensives.
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- ACYLOXYKETONE SUBSTITUTED IMINO AND AMINO ACIDS
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Acyloxyketone substituted imino and amino acids of the formula STR1 are disclosed. These compounds are useful hypotensive agents due to their angiotensin converting enzyme inhibition activity.
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