- Preparation method of ceftobiprole intermediate (R)-1-benzyl-3-aminopyrrolidine
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The invention discloses a preparation method of a ceftobiprole intermediate, namely (R)-1-benzyl-3-aminopyrrolidine. The preparation method specifically comprises the following steps: with D-asparticacid as an initial raw material, carrying out amino protection, esterification, reduction, bromination cyclization and 3-amino protection removal successively to obtain (R)-1-benzyl-3-aminopyrrolidine. According to the method, the defects that raw materials for preparing (R)-1-benzyl-3-aminopyrrolidine are expensive, high temperature and high pressure are needed, precious metal is used for catalysis and the like in the prior art are overcome. All the materials used in the invention are cheap and easily available, so cost is low; and reactions can be carried out at normal temperature, so energyconsumption is low, industrial production is facilitated, and pollution is small.
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Paragraph 0022; 0035-0037; 0048-0050; 0061-0063
(2020/09/16)
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- Synthesis and anticonvulsant evaluation of (R)-and (S)-3-carbobenzyloxy- amino-1-oxysuccinimides
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A series of (R)-and (S)-3-carbobenzyloxy-amino-1-oxysuccinimides (5a-d) [(S)-3-carbobenzyloxy-amino-1-benzoyloxysuccinimde, (R)-3-carbobenzyloxy-amino- 1-acetyloxysuccinimde, (R)-3-carbobenzyloxy-amino-1,4-nitrobenzoyloxysuccinimde, (R)-3-carbobenzyloxyamino-1,4-fluorobenzoyloxysuccinimde] were synthesized and investigated their anticonvulsant activities in maximal electric shock seizure test and pentylenetetrazole induced seizure test.
- Lee, Do-Hun
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p. 5948 - 5950
(2013/07/26)
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- Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents
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A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC2), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis.
- Eswaran, Sumesh,Adhikari, Airody Vasudeva,Pal, Nishith K.,Chowdhury, Imran H.
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supporting information; experimental part
p. 1040 - 1044
(2010/06/14)
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- ARYLSULFONAMIDE COMPOUNDS
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The invention relates generally to small molecules that mimic the biological activity of certain peptides and proteins, to compositions containing them and to their use. In particular, the invention relates to compounds of the general formula (I) that mim
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Page/Page column 31-32; 34-35
(2008/12/05)
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- Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers
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(Chemical Equation Presented) Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative 4, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities. The reaction preserves the stereochemical integrity of the substrates. The reactions are high yielding, and the workup is convenient.
- Li, Bryan,Berliner, Martin,Buzon, Richard,Chiu, Charles K.-F.,Colgan, Stephen T.,Kaneko, Takushi,Keene, Nandell,Kissel, William,Le, Tung,Leeman, Kyle R.,Marquez, Brian,Morris, Ronald,Newell, Lisa,Wunderwald, Silke,Witt, Michael,Weaver, John,Zhang, Zhijun,Zhang, Zhongli
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p. 9045 - 9050
(2007/10/03)
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- N substituted 3-amino-2,2-di-c-alkyl-1,4-butyrolactones and 1,4-thiobutyrolactones for use as promoter of γ-aminobutyric acid activity and for treating nervous disorders and preparation method
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The invention concerns compounds represented by general formula (I) wherein: Z represents a sulfur or oxygen atom; the groups R1 and R2, identical or different, represent each a alkyl group or an alkenyl group; X represents a CO, a CO2, an SO, or an SO2and the group R represents an alkyl, aryl, alkenyl, or aralkyl group, provided that when Z represents an oxygen atom, X an SO2and R a group (a), R1 and R2 do not both represent the methyl group. The invention also concerns methods for preparing said compounds, pharmaceutical compositions containing them and their use as promoter of γ-aminobutyric acid and as medicine particularly designed for treating nervous disorders.
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Page column 13-14
(2010/02/06)
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- Geometrical optimisation of 1,1′-binaphthalene receptors for enantioselective molecular recognition of excitatory amino acid derivatives
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A series of optically active 1,1′-binaphthalene-derived receptors with N-(pyridine-2,6-diyl)acetamide [CONH(py)] H-bonding sites in the 6,6′-positions has been prepared for the enantioselective complexation of the N-carbobenzyloxy (Cbz)-protected excitatory amino acids aspartic (Asp) and glutamic (Glu) acid via two COOH ... CONH(py) H-bonding arrays and additional secondary bonding interactions. The conformational homogeneity of the receptors is enhanced by locking the dihedral angle θ about the chirality axis through the C(1)-C(1′) bond of the 1,1′-binaphthalene moiety either by bridging the 2,2′-positions or by attaching bulky substituents to these centres. Computer modelling has shown that bridging is more efficient in locking this dihedral angle than the introduction of bulky substituents, and these predictions have been confirmed by 1H NMR binding studies in CDCl3 and in CDCl3-CD3OD 99.8:0.2. Plots of the enantioselectivity Δ(ΔG°) (difference in stability between diastereoisomeric complexes) in the recognition by the bridged receptors as a function of the enforced dihedral angle θ are peak-shaped, and the highest values have been measured in CDCl3 (300 K) for the complexation of the enantiomers of N-Cbz-Asp [Δ(ΔG°) = 6.9 kJ mol-1] and N-Cbz-Glu [Δ(ΔG°) = 5.2 kJ mol-1] by (R)-21 (θ = 86 ± 4°). The more stable diastereoisomeric complexes are highly structured, and tight host-guest bonding has been confirmed by the observation of up to five intermolecular NOEs. Enforcing the conformational homogeneity by bridging represents a new general principle for improving the chiral recognition potential of 1,1′-binaphthalene receptors.
- Lustenberger, Philipp,Martinborough, Esther,Mordasini Denti, Tiziana,Diederich, Francois
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p. 747 - 761
(2007/10/03)
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- Design and preparation of serine-threonine protein phosphatase inhibitors based upon the nodularin and microcystin toxin structures: Part 1. Evaluation of key inhibitory features and synthesis of a rationally stripped-down nodularin macrocycle
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The natural nodularin and microcystin toxins are powerful but non-selective inhibitors of the ubiquitous and structurally related eukaryotic Ser-Thr protein phosphatases, PP1 and PP2A, enzymes that are intimately involved in controlling cellular metabolism. Both families of toxin are cyclic tri-isopeptides typified by the presence of two free carboxylic acid groups, a dehydroamino acid moiety, and a large, rigid exocyclic lipophilic side-chain. To learn how to design specific inhibitors for each enzyme, the nature of specific interactions with potential inhibitor-conferring moieties in the toxin was considered. Borohydride reduction of the dehydroalanine residue present in microcystin-LR, a potential Michael acceptor, gave two diastereoisomeric dihydromicrocystin products. Each of these displayed subnanomolar activities as inhibitors for PP2A, as for the parent compound, indicating that the dehydroamino acid residue in microcystin and, probably, in nodularin, is not essential for activity. Other conserved features appeared to be required to confer activity, hence strategies towards the synthesis of simplified non-dehydroamino acid-containing analogues of each macrocycle type were considered. In each case it was planned to elaborate the lipophilic side-chain functionality after the formation of the macrocyclic ring. In order to synthesize the precursor nodularin-type macrolactam, two peptide-bond disconnections of the ring were investigated using a model system, cyclo-[β-Ala-(R)-Glu-α-OMe-γ-Sar-(R)-Asp-α-OMe-β-(S) -Phe-], one bond disconnecting between the sarcosine carboxy group and the (2R)-Asp N-atom and the other disconnecting between the (2R)-Asp β-carboxy group and the (2S)-PhC N-atom. Preparation of the linear precursors was achieved using solution-phase chemistry without incident. Macrolactamisation via the displacement of the β-pentafluorophenyl ester of the (2R)-Asp α-methyl ester residue by the free amino group of the (2S)-phenylalanine residue proceeded in excellent yield (89%), but the alternative strategy failed. Application of the successful macrolactamisation strategy to other nodularin macrocycles and to the construction of the microcystin-type macrocycle is described in the following article.
- Mehrotra, Amit P.,Webster, Kerri L.,Gani, David
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p. 2495 - 2511
(2007/10/03)
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- Chiral quinolone intermediates
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Chiral compounds having the formulae STR1 useful in the synthesis of quinolone intermediates.
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- NMDA antagonists
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The present invention is directed to a new class of 4-(oxoalkyl)phosphono, 4(oxime alkyl)phosphono, or 4-(hydrazine alkyl)phosphono, 2-piperazine carboxylic derivatives that are useful as NMDA antagonists
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- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
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A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
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p. 1125 - 1128
(2007/10/02)
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- PAPAIN-ASSISTED RESOLUTION OF NATURAL AND XENOBIOTIC α-AMINO ACIDS
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A new and convenient method for the preparation of pure enantiomers of α-amino acids is described.Industrial papain, catalyzes the synthesis of L-Z-amino acid ethyl esters in ethanolic medium, with good yields.These esters are obtained from DL-Z-amino acids with 100percent optical purity.Unreactive D-Z-amino acids are readily isolated from reaction medium.Physical constants of natural and xenobiotic L-Z-amino acid esters and D-Z-amino acids are described.
- Moriniere, J. L.,Danree, B.,Lemoine, J.,Guy, A.
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p. 441 - 444
(2007/10/02)
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