- Stereoselective cycloaddition of monosubstituted ketene to a methyl glyoxylate- and threonine-derived imine: Synthesis of optically pure β-lactamic α-amino ester with high functionality
-
The reaction of chloroacetyl chloride and triethylamine with a chiral imine derived from the combination of methyl glyoxylate and protected L-threonine gave two optically active α-amino acid derivatives with a cis-substituted β-lactam skeleton in a 72:28 ratio. The major product is obtained in 59% yield by simple crystallisation.
- Mignani,Mouysset,Le Roy,Stella
-
-
Read Online
- (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative as well as preparation method and application thereof
-
The invention discloses a (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative shown as a formula (I) or an optical isomer, a diastereomer and racemate mixture and pharmaceutically acceptable salt thereof as well as a preparation method and application of the (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative. It is shown by comparison of results of a positive control group and a model group on lymphedema prevention experiments that the compound disclosed in the invention shows obvious anti-edema activity.
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-
Paragraph 0047-0048; 0054-0056
(2021/02/10)
-
- NOVEL COMPOUNDS AND THEIR USE
-
The present invention provides compounds of the general formula (I) or a pharmaceutically acceptable prodrugs, salts and/or solvates thereof, wherein LHS is selected from the group consisting of LHSa and LHSb And wherein, the asterisk (*) marks the point of attachment; These compounds exhibit antibacterial activity against Gram-negative and Gram-positive bacteria, especially S. aureus, E. coli, K. pneumoniae and A. baumannii. Pharmaceutical compositions containing these compounds, therapeutic uses thereof and methods for manufacturing the same are also provided.
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Page/Page column 76-77
(2021/06/26)
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- Bicyclic Lactams Derived from Serine or Cysteine and 2-Methylpropanal
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Bicyclic lactams may be prepared from serine or cysteine and 2-methylpropanal; the resulting S, N -heterocycles are more stable than the corresponding O, N -heterocycles but both are synthetic intermediates capable of further elaboration.
- Bagum, Halima,Christensen, Kirsten E.,Genov, Miroslav,Moloney, Mark G.,Pretsch, Alexander,Pretsch, Dagmar,Shire, Bethany R.
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supporting information
p. 378 - 382
(2020/02/27)
-
- Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile
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Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a–4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1H NMR and 13C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+/K+-ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.
- Khan, Muhammad T.,Nadeem, Humaira,Khan, Arif-ullah,Abbas, Muzaffar,Arif, Muazzam,Malik, Nadia Shamshad,Malik, Zulkifal,Javed, Ibrahim
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p. 1057 - 1072
(2020/08/13)
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- A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor γbinding Properties and Biological Activities
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A proprietary library of novel N-Aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound 3a that possesses weak proadipogenic and peroxisome proliferator-Activated receptor γ(PPARI) activating properties. The systematic optimization of 3a, in order to improve its PPARγagonist activity, led to the synthesis of compound 7j (N-Aryl-substituted valine derivative) that possesses dual PPARI/PPARα agonistic activity. Structural and kinetic analyses reveal that 7j occupies the typical ligand binding domain of the PPARγagonists with, however, a unique high-Affinity binding mode. Furthermore, 7j is highly effective in preventing cyclin-dependent kinase 5-mediated phosphorylation of PPARγserine 273. Although less proadipogenic than rosiglitazone, 7j significantly increases adipocyte insulin-stimulated glucose uptake and efficiently promotes white-To-brown adipocyte conversion. In addition, 7j prevents oleic acid-induced lipid accumulation in hepatoma cells. The unique biochemical properties and biological activities of compound 7j suggest that it would be a promising candidate for the development of compounds to reduce insulin resistance, obesity, and nonalcoholic fatty liver disease.
- Peiretti, Franck,Montanari, Roberta,Capelli, Davide,Bonardo, Bernadette,Colson, Cécilia,Amri, Ez-Zoubir,Grimaldi, Marina,Balaguer, Patrick,Ito, Keiichi,Roeder, Robert G.,Pochetti, Giorgio,Brunel, Jean Michel
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p. 13124 - 13139
(2020/12/02)
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- L-threonine-linked dihydroartemisinin-fluoroquinolone conjugates, intermediates thereof, and preparation methods and uses of conjugates and intermediates
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The invention discloses L-threonine-linked dihydroartemisinin-fluoroquinolone conjugates represented by formula I, intermediates represented by formula II, preparation methods of the compounds of formula I and formula II, and uses of the compounds of the formula I in the preparation of drugs for resisting mycobacterium tuberculosis or/and drugs for lowering blood lipids.
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Paragraph 0113-0119
(2019/12/08)
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- Polypeptide raw material N-fluorenylmethoxycarbonyl-O-tert-butyl threonine preparation method
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The invention discloses a polypeptide raw material N-fluorenylmethoxycarbonyl-O-tert-butyl threonine preparation method, and mainly solves the technical problems of complexity, long cycle, more wastegas, waste water and industrial residues, high cost, high dangerousness and the like in an original process. The preparation method includes the steps: first, suspending threonine in methanol, reducing temperature, dropping thionyl chloride and then removing solvents by concentration after temperature reaction to obtain threonine methyl ester hydrochloride; second, dissolving the threonine methylester hydrochloride in methylene dichloride, leading in isobutene, concentrating sulfuric acid and performing sealed reaction treatment to obtain oily O-tert-butyl threonine methyl ester; third, dissolving the O-tert-butyl threonine methyl ester in water and acetone, adding sodium hydroxide, enabling pH (potential of hydrogen) to be 11-12, performing reaction to obtain O-tert-butyl threonine solution, adding 9-fluorenylmethyl-N-succinimidyl carbonate, maintaining the pH of 8-9 of a system by the aid of alkali liquor, performing washing acidification extraction after reaction and performing treatment to obtain N-fluorenylmethoxycarbonyl-O-tert-butyl threonine serving as a final product.
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Paragraph 0012-0014
(2019/01/23)
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- IMMUNOPROTEASOME INHIBITORS
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Provided herein are compounds, such as a compound of Formula (I), or a pharmaceutically acceptable salt thereof, that are immunoproteasome (such as LMP2 and LMP7) inhibitors. The compounds described herein can be useful for the treatment of diseases treatable by inhibition of immunoproteasomes. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Paragraph 0243
(2019/06/13)
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- Synthetic Access to 3-Substituted Pyroglutamic Acids from Tetramate Derivatives of Serine, Threonine, allo-Threonine, and Cysteine
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A general route which provides direct access to pyroglutamates from tetramates, making use of Suzuki coupling on an enol mesylate, followed by reduction, is reported. This work permits direct scaffold hopping from tetramate to substituted pyroglutamates. Some compounds in the library showed modest antibacterial activity against Gram-positive bacteria.
- Bagum, Halima,Christensen, Kirsten E.,Genov, Miroslav,Pretsch, Alexander,Pretsch, Dagmar,Moloney, Mark G.
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p. 10257 - 10279
(2019/08/20)
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- Singlet Oxygen Photooxidation of Peptidic Oxazoles and Thiazoles
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Oxazoles and thiazoles are commonly found moieties in nonribosomal peptides (NRPs) and ribosomally synthesized post-translationally modified peptides (RiPPs), which are important biomolecules present in the environment and in natural waters. From previous studies, they seem susceptible to oxidation by singlet oxygen (1O2); therefore, we designed and synthesized model oxazole- and thiazole-peptides and measured their1O2 bimolecular reaction rate constants, showing slow photooxidation under environmental conditions. We reasoned their stability through the electron-withdrawing effect of the carboxamide substituent. Reaction products were elucidated and support a reaction mechanism involving cycloaddition followed by a series of rearrangements. The first1O2 bimolecular reaction rate constant for a RiPP, the thiazole-containing peptide Aerucyclamide A, was measured and found in good agreement with the model peptide's rate constant, highlighting the potential of using model peptides to study the transformations of other environmentally relevant NRPs and RiPPs.
- Manfrin, Alessandro,Borduas-Dedekind, Nadine,Lau, Kate,McNeill, Kristopher
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p. 2439 - 2447
(2019/02/26)
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- Synthetic access to 3,4-disubstituted pyroglutamates from tetramate derivatives from serine, allo-threonine and cysteine
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A route allowing the conversion of substituted tetramates to 3,4-disubstituted pyroglutamates, making use of Suzuki coupling on an enol mesylate, followed by reduction, is both general and fully stereoselective.
- Bagum, Halima,Christensen, Kirsten E.,Genov, Miroslav,Pretsch, Alexander,Pretsch, Dagmar,Moloney, Mark G.
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- Design, synthesis, and cytotoxicity evaluation of threonine-based galactoceramide with aromatic groups and various fatty-acyl side chains
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Abstract: In galactoceramides, presence of fatty-acyl group on amide moiety or phytosphingosine group is some of the important features that influence the cytotoxicity. Continuous efforts are in progress to modify the fatty-acid moiety and phytosphingosine group present on the galactoceramides to enhance the cytotoxic potential of these compounds. Hence, in the present study, threonine-based β-galactoceramide and its derivatives were prepared by modifying the fatty-acyl group on amide moiety with different fatty-acyl moieties and aromatic acids employing trichloroacetimidate methodology. The structurally related threonine-based ceramide part was synthesized in multi-step process using different reagents. The ceramide part was glycosylated with galactose using trichloroacetimidate as donor. Further, all the synthesized compounds were evaluated for in vitro cytotoxicity against three cancer cell lines and one normal cell line and all the compounds exhibited good to moderate cytotoxicity against all the tested cancer cell lines. In aromatic derivatives, the compound 8i exhibited promising activity against MCF7, A549 and HeLa cancer cell lines with IC50 values of 14.08, 14.78, and 16.70 μM, respectively. In fatty-acid derivatives, two compounds exhibited promising activity, i.e., compound 8m against HeLa with IC50 value 16.34 μM and compound 8n against MCF7 with IC50 value 18.05 μM. Based on structure–activity relationship, aromatic acid derivatives exhibited potential activity as compared to fatty-acid derivatives. Further, the influence of some of the key factors such as spacer chain length between aromatic residue and amide functional group, methoxy substituents on aryl group, terminal unsaturation of fatty acid and branching chain effect on the cytotoxicity are discussed.
- Vudhgiri, Srikanth,Routhu, Sunitha Rani,Kumar, C. Ganesh,Prasad,Reddy Jala, Ram Chandra
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p. 285 - 307
(2018/04/17)
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- Radical-mediated intramolecular β-C(sp3)-H amidation of alkylimidates: Facile synthesis of 1,2-amino alcohols
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A new radical-mediated intramolecular β-C(sp3)-H amidation reaction of O-alkyl trichloro- or arylimidates is reported. Various oxazolines were efficiently prepared from easily accessible alcohol starting materials. The trichloro-oxazoline products can be hydrolyzed under mild conditions to give valuable 1,2-amino alcohols. This amidation reaction exhibits a broad substrate scope and good functional group tolerance, and offers a powerful means for the C(sp3)-H functionalization of alcohols. Mechanistic studies suggest that a sequence of 1,5-HAT of an imidate radical, iodination and cyclization might be operative.
- Mou, Xue-Qing,Chen, Xiang-Yu,Chen, Gong,He, Gang
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p. 515 - 518
(2018/01/19)
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- Synthesis method of Fmoc-O-tert-butyl-L-threoninol
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The present invention relates to a synthesis method of Fmoc-O-tert-butyl-L-threoninol, and mainly solves the technical problems that in a process of Fmoc-thr(tbu)-oh reduction by sodium borohydride, the reaction temperature is strictly required and a FMoc protecting group is decomposed, resulting in low yield and high cost. The synthesis method of the invention comprises the following steps: a. L-threonine reacts with thionyl chloride to form L-threonine methyl ester hydrochloride; b. the L-threonine methyl ester hydrochloride under the action of sodium hydroxide is reacted with benzyl chloroformate to produce z-thr-ome; c. the Z-thr-ome reacts with introduced isobutene in the presence of methylene chloride and concentrated sulfuric acid, and alkali adjustment treatment is carried out to obtain z-thr (tbu)-ome; d. in the presence of acetone and water, the Z-thr(tbu)-ome is saponified with added alkali to obtain z-thr(tbu)-oh; e. the Z-thr(tbu)-oh is reduced to z-thr(tbu)-ol by sodium borohydride in tetrahydrofuran; f. the z-thr(tbu)-ol is hydrogenated in methanol to obtain H-thr(tbu)-ol; and g. N-(9-fluorenylmethoxycarbonyloxy)succinimide is added to the H-thr(tbu)-ol to obtain the Fmoc-O-tert-butyl -L-threoninol.
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Paragraph 0015
(2017/07/12)
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- Carbostyril carboxylic compounds and intermediates, preparation method and application thereof
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The invention discloses carbostyril carboxylic compounds and hydrochlorides thereof and also discloses a preparation method of the compounds and the hydrochlorides thereof as well as an application of the compounds and the hydrochlorides thereof in preparing gram-positive bacterium-preventing or gram-negative bacterium-preventing drugs. Moreover, the invention discloses intermediates for preparing the compounds and a preparation method of the intermediates.
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Paragraph 0163-0167
(2017/07/12)
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- Total Synthesis of Pseudomonas aeruginosa 1244 Pilin Glycan via de Novo Synthesis of Pseudaminic Acid
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Pseudaminic acid (Pse) is a nonulosonic acid unique to bacterial species, found as a component of important cell surface glycans and glycoproteins in various pathogenic species, such as the critical hospital threat Pseudomonas aeruginosa. Herein we present the development of a facile and scalable de novo synthesis of Pse and its functionalized derivatives from easily available Cbz-l-allo-threonine methyl ester (16 steps in 11% yield). The key reactions in our de novo synthesis involve the diastereoselective glycine thioester isonitrile-based aldol-type reaction to create the 1,3-anti-diamino skeleton, followed by the Fukuyama reduction and the indium-mediated Barbier-type allylation. Moreover, we have studied the glycosylation of the Pse glycosyl donors and identified the structural determinants for its glycosylation diastereoselectivity, which enabled us to complete the total synthesis of P. aeruginosa 1244 pilin trisaccharide α-5NβOHC47NFmPse-(2→4)-β-Xyl-(1→3)-FucNAc.
- Liu, Han,Zhang, Yanfeng,Wei, Ruohan,Andolina, Gloria,Li, Xuechen
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supporting information
p. 13420 - 13428
(2017/10/05)
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- Synthesis of sialic acid derivatives based on chiral substrate-controlled stereoselective aldol reactions using pyruvic acid oxabicyclo[2.2.2]octyl orthoester
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The synthesis of sialic acids and their analogs was accomplished based on substrate-controlled asymmetric aldol reactions between sterically complicated aldehydes easily prepared from commercially available carbohydrates and a novel pyruvic acid oxabicyclo[2.2.2]octyl orthoester. Systematic aldol reaction studies using chiral aldehydes revealed that α,β,γ-benzyloxy-substituted aldehydes with an α,β-anti relative configuration preferentially provided the Felkin products with the 4,5-anti configuration with high diastereoselectivity. The relative β,γ-configuration in α,β,γ-benzyloxy-substituted aldehydes with an α,β-syn arrangement exerted a secondary effect on the diastereoselectivity of the stereogenic center formed in aldol reactions, and α,β-syn-β,γ-anti benzyloxyaldehyde exhibited superior diastereoselectivity to α,β-syn-β,γ-syn benzyloxyaldehyde to yield the Felkin products.
- Norimura, Yusuke,Yamamoto, Daisuke,Makino, Kazuishi
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p. 640 - 648
(2017/01/25)
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- Total Synthesis of (-)-Hymenosetin
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The 3-decalinoyltetramic acid (-)-hymenosetin and its N-methyl analogue were prepared in 11 and 8 steps, respectively, from (+)-citronellal using an intramolecular Diels-Alder reaction as the key step. This method represents the first example for the synthesis of a 3-decalinoyltetramic acid with a free NH moiety. The stereochemistry of the title compound, an unnatural diastereomer, and of a decalin building block was studied in detail using circular dichroism spectroscopy in the IR and UV/VIS freqeuncy range. This allowed to determine the absolute configuration of the natural product and to plan the synthetic route.
- Kauhl, Ulrich,Andernach, Lars,Weck, Stefan,Sandjo, Louis P.,Jacob, Stefan,Thines, Eckhard,Opatz, Till
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p. 215 - 228
(2016/01/15)
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- Preparation of the optically pure N-methyl amino ester method and product
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The invention belongs to the field of organic synthesis of amino acids and discloses a method for preparing optically pure N-methyl amino-acid ester. The method comprises the following steps of carrying out esterification reaction on amino acid as a starting raw material and aldehyde to form an imine intermediate, carrying out reductive amination in the presence of palladium carbon, and carrying out hydrogenation and debenzylation to finally synthesize optically pure N-methyl amino-acid ester. The method has the advantages of simplicity in method, mild reaction conditions and good adaptability and side chains of D-type or L-type amino acid do not need to be protected.
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Paragraph 0045-0047
(2017/04/13)
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- Dehydrodipeptide Hydrogelators Containing Naproxen N-Capped Tryptophan: Self-Assembly, Hydrogel Characterization, and Evaluation as Potential Drug Nanocarriers
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In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and F?rster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.
- Vila?a, Helena,Hortel?o, Ana C. L.,Castanheira, Elisabete M. S.,Queiroz, Maria-Jo?o R. P.,Hilliou, Loic,Hamley, Ian W.,Martins, José A.,Ferreira, Paula M. T.
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p. 3562 - 3573
(2015/11/17)
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- Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards β-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates
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Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para- methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding β-methyl azalanthionines have, so far, been unsuccessful.
- O'Brien, Keith,ó Proinsias, Keith,Kelleher, Fintan
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p. 5082 - 5092
(2014/07/08)
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- Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards β-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates
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Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para-methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding β-methyl azalanthionines have, so far, been unsuccessful.
- O'Brien, Keith,ó Proinsias, Keith,Kelleher, Fintan
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p. 5082 - 5092
(2014/12/10)
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- A 3,4-trans-fused cyclic protecting group facilitates α-selective catalytic synthesis of 2-deoxyglycosides
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A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high α-selectivity and yields (77-97 %) using a trans-fused cyclic 3,4-O-disiloxane protecting group and TsOH·H2O (1 mol %) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side-chain conformation augments the selectivity.
- Balmond, Edward I.,Benito-Alifonso, David,Coe, Diane M.,Alder, Roger W.,McGarrigle, Eoghan M.,Galan, M. Carmen
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supporting information
p. 8190 - 8194
(2014/08/18)
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- Cycloforskamide, a cytotoxic macrocyclic peptide from the sea slug Pleurobranchus forskalii
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A macrocylic dodecapeptide, cycloforskamide, was isolated from the sea slug Pleurobranchus forskalii, collected off Ishigaki Island, Japan. Its planar structure was deduced by extensive NMR analyses and was further confirmed by MS/MS fragmentation analyses. Finally, the absolute configuration was determined by total hydrolysis and chiral-phase gas chromatographic analysis. This novel dodecapeptide contains three d-amino acids and three thiazoline heterocycles and exhibits cytotoxicity against murine leukemia P388 cells, with an IC 50 of 5.8 μM.
- Tan, Karen Co,Wakimoto, Toshiyuki,Takada, Kentaro,Ohtsuki, Takashi,Uchiyama, Nahoko,Goda, Yukihiro,Abe, Ikuro
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p. 1388 - 1391
(2013/08/23)
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- Exploring the UDP pocket of LpxC through amino acid analogs
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Lipopolysaccharide (LPS) biosynthesis is an attractive antibacterial target as it is both conserved and essential for the survival of key pathogenic bacteria. Lipid A is the hydrophobic anchor for LPS and a key structural component of the outer membrane of Gram-negative bacteria. Lipid A biosynthesis is performed in part by a unique zinc dependent metalloamidase, LpxC (UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase), which catalyzes the first non-reversible step in lipid A biosynthesis. The UDP portion of the LpxC substrate-binding pocket has been relatively unexplored. We have designed and evaluated a series of hydroxamate based inhibitors which explore the SAR of substitutions directed into the UDP pocket with a range of substituted α-amino acid based linkers. We also provide the first wild type structure of Pseudomonas aeruginosa LpxC which was utilized in the design of many of these analogs.
- Hale, Michael R.,Hill, Pamela,Lahiri, Sushmita,Miller, Matthew D.,Ross, Philip,Alm, Richard,Gao, Ning,Kutschke, Amy,Johnstone, Michele,Prince, Bryan,Thresher, Jason,Yang, Wei
-
supporting information
p. 2362 - 2367
(2013/05/09)
-
- Synthesis of some n-aryl α-Amino acids using diaryliodonium salts
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Bis[(3'-methoxycarbonyl)phenyl]iodonium bromide (4a), bis (4'-methoxyphenyl)iodonium iodide (4b) and bis (4'-acetamidophenyl)iodonium iodide (4c) were employed for the first time in the arylation of α-amino acid methyl esters. Yields of the synthesised products 5, 6 and 7 were good to high. These were then hydrolyzed to the corresponding N-aryl α-amino acids 8 and 9. The chiral integrity of the amino acids was maintained throughout the reaction sequence as confirmed by the synthesis of chiral tripeptide 10 and dipeptides 11. The structures of the new compounds were confirmed by IR, 1H and 13C NMR in addition to CHN microanalysis or high resolution mass spectrometry.
- Mckerrow, Jason D.,Al-Rawi, Jasim M.,Brooks, Peter
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body text
p. 1227 - 1236
(2012/09/22)
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- Synthesis and SAR of b-annulated 1,4-dihydropyridines define cardiomyogenic compounds as novel inhibitors of TGFβ signaling
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A medium-throughput murine embryonic stem cell (mESC)-based high-content screening of 17000 small molecules for cardiogenesis led to the identification of a b-annulated 1,4-dihydropyridine (1,4-DHP) that inhibited transforming growth factor β (TGFβ)/Smad signaling by clearing the type II TGFβ receptor from the cell surface. Because this is an unprecedented mechanism of action, we explored the series' structure-activity relationship (SAR) based on TGFβ inhibition, and evaluated SAR aspects for cell-surface clearance of TGFβ receptor II (TGFBR2) and for biological activity in mESCs. We determined a pharmacophore and generated 1,4-DHPs with IC 50s for TGFβ inhibition in the nanomolar range (e.g., compound 28, 170 nM). Stereochemical consequences of a chiral center at the 4-position was evaluated, revealing 10- to 15-fold more potent TGFβ inhibition for the (+)- than the (-) enantiomer. This stereopreference was not observed for the low level inhibition against Activin A signaling and was reversed for effects on calcium handling in HL-1 cells.
- Schade, Dennis,Lanier, Marion,Willems, Erik,Okolotowicz, Karl,Bushway, Paul,Wahlquist, Christine,Gilley, Cynthia,Mercola, Mark,Cashman, John R.
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supporting information
p. 9946 - 9957
(2013/01/16)
-
- Syntheses, structures and antibiotic activities of LpxC inhibitors based on the diacetylene scaffold
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Compounds inhibiting LpxC in the lipid A biosynthetic pathway are promising leads for novel antibiotics against multidrug-resistant Gram-negative pathogens. We report the syntheses and structural and biochemical characterizations of LpxC inhibitors based on a diphenyl-diacetylene (1,4-diphenyl-1,3-butadiyne) threonyl-hydroxamate scaffold. These studies provide a molecular interpretation for the differential antibiotic activities of compounds with a substituted distal phenyl ring as well as the absolute stereochemical requirement at the C2, but not C3, position of the threonyl group.
- Liang, Xiaofei,Lee, Chul-Jin,Chen, Xin,Chung, Hak Suk,Zeng, Daina,Raetz, Christian R.H.,Li, Yaoxian,Zhou, Pei,Toone, Eric J.
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supporting information; experimental part
p. 852 - 860
(2011/03/19)
-
- Synthesis and characterization of tailorable biodegradable thermoresponsive methacryloylamide polymers based on l-serine and l-threonine alkyl esters
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A series of monomers based on the methyl, ethyl, and isopropyl esters of Nα-(methacryloyl)-serine and -threonine were synthesized, and used in an AIBN-initiated radical polymerization reaction to yield polymers with an Mn ranging between 6.6 and 23.8 kDa. The newly synthesized polymers showed LCST behavior in aqueous solution that could be tailored by subtle variations of the hydrophobicity of the monomers to obtain a broad range of cloud points between 1.5 and >100°C. According to HPLC, the hydrolytic t1/2-values (pH 7.4 at 37°C) of the monomers were found to be 5, 12, and 40 days of the methyl, ethyl, and isopropyl esters, respectively, while the hydrolysis rate of poly[Nα-(methacryloyl)-Ser-OMe] and poly[Nα-(methacryloyl)-Thr-OMe] was found to be significantly lower compared to the corresponding monomers. In order to obtain thermoresponsive nanoparticles, Nα-(methacryloyl)-Thr-OEt was polymerized with (PEG monomethyl ether 5000)2-ABCPA as macroinitiator to yield an amphiphilic block co-polymer, poly[Nα-(methacryloyl)-Thr-OEt]-b-(PEG monomethyl ether 5000), which forms particles of 300 nm at a temperature higher than its cloud point of 24°C. Incubation at physiological conditions induced ester hydrolysis resulting in a destabilization of the particles making these particles suitable for drug delivery purposes.
- van Dijk, Maarten,Postma, Tobias M.,Rijkers, Dirk T.S.,Liskamp, Rob M.J.,van Nostrum, Cornelus F.,Hennink, Wim E.
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experimental part
p. 2479 - 2485
(2011/10/09)
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- Use of diphenyliodonium bromide in the synthesis of some N-phenyl-amino acids
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The N-phenyl methyl esters 4 of glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, serine, threonine, tyrosine, aspartic acid, and glutamic acid have been synthesized in good to excellent yields using diphenyliodonium bromide, AgNO3, and a catalytic amount of CuBr starting from the relevant amino acid ester. The chiral integrity of the amino acids 5 was maintained during these reactions, which were confirmed by the synthesis of dipeptide for each N-phenyl amino acid. The structures of the new compounds were confirmed by the analysis of their IR, 1H, and 13C NMR spectra in addition to CHN microanalysis or high-resolution mass spectrometry for the new N-phenyl amino acids 5 and the esters 4.
- McKerrow, Jason D.,Al-Rawi, Jasim M. A.,Brooks, Peter
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experimental part
p. 1161 - 1179
(2010/04/28)
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- SAR and molecular mechanism study of novel acylhydrazone compounds targeting HIV-1 CA
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We synthesized a series of acylhydrazone compounds bearing naturally occurring amino acids' side chains as HIV assembly inhibitors. Biological evaluation indicated that the compounds had anti-SIV and capsid assembly inhibitory activities. The structure-activity relationship (SAR) study showed that compounds bearing proper aromatic side chains had potential antiviral activities. The molecular modeling experiments revealed the molecular mechanism that they could bind to CA in the same manner as CAP-1 and occupy two more grooves.
- Jin, Yinxue,Tan, Zhiwu,He, Meizi,Tian, Baohe,Tang, Shixing,Hewlett, Indira,Yang, Ming
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experimental part
p. 2135 - 2140
(2010/06/12)
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- Facile synthesis of β-amino disulfides, cystines, and their direct incorporation into peptides
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Herein, we report a simple and efficient methodology for the synthesis of β-amino disulfides by regioselective ring opening of sulfamidates with benzyltriethylammonium tetrathiomolybdate [BnNEt3] 2MoS4. Stability and reactivity of different protecting groups under the reaction conditions have been discussed. This methodology has also been extended to serine and threonine derived sulfamidates to furnish cystine and 3,3′-dimethyl cystine derivatives. Georg Thieme Verlag.
- Nasir Baig,Kanimozhi, Catherine K.,Sudhir, V. Sai,Chandrasekaran, Srinivasan
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scheme or table
p. 1227 - 1232
(2009/09/06)
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- Asymmetric syntheses and Wnt signal inhibitory activity of melleumin A and four analogues of melleumins A and B
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The first total synthesis of melleumin A and four analogues of melleumins A and B is described. The N-acyl L-Thr-Gly/β-hydroxy-γ-amino acid coupling/macrolactamization strategy allowed the efficient assembly of the three segments being free of epimerization. While the Jouin-Castro method with minor modification allows a rapid entrance to the key syn-β-hy-droxy-y-amino acid segment, required for the synthesis of melleumin A, an extension of our malimide-based methodology using a changed N-protecting group affords a flexible access to several anti-β-hydroxy-γ-amino acids, and hence analogues of melleumins A and B. Among them, unnatural 4-epi-melleumin B (2a) exhibits a modest inhibitory activity on Wnt signaling. The total synthesis of melleumin A allowed confirmation of its full structure.
- Luo, Jie-Min,Dai, Chao-Feng,Lin, Shu-Yong,Huang, Pei-Qiang
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supporting information; experimental part
p. 328 - 335
(2010/04/23)
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- An improved method for culturing Streptomyces sahachiroi: Biosynthetic origin of the enol fragment of azinomycin B
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Azinomycin B is an environmental DNA crosslinking agent produced by the soil microorganism Streptomyces sahachiroi. While the agent displays potent cytotoxic activities against leukemic cell lines and animal mouse models, the lack of a consistent supply of the natural product has hampered detailed biological investigations on the compound, including its mode of action and biosynthesis. We report here a significant methodological improvement in the culturing of the bacterium, which allows reliable and steady production of the natural product in good yields. The key experimental step involves the culturing of the strain on dehydrated plates, followed by the generation of a two-stage starter culture and subsequent fermentation of the strain under nutrient-starved conditions. We illustrate use of this culture system by investigating the formation of the enol fragment of the molecule in isotopic labeling experiments with threonine and several advanced precursors (β-ketoamino acid 3, β-hydroxyamino aldehyde 4, and β-ketoaminoaldehyde 5). The results unequivocally show that threonine is the most advanced precursor accepted by the NRPS (non-ribosomal peptidyl synthetase) machinery for final processing and construction of the enol moiety of the natural product.
- Kelly, Gilbert T.,Sharma, Vasudha,Watanabe, Coran M.H.
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- Toward the development of chemoprevention agents (III): Synthesis and anti-inflammatory activities of a new class of 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes
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A new series of 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes were designed and synthesized. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Sixteen of these new compounds exhibited comparable or better anti-inflammatory activities than aspirin suggesting that they can be further developed as potential anti-inflammatory drug leads. In addition, treatment with these anti-inflammatory agents did not prolong tail bleeding time in mice. The structure/activity relationships were also analyzed among these compounds. Considering their good efficacy and safety profiles, some 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes are worthy to be explored further in assessing the possible link between anti-inflammation and cancer prevention.
- Bi, Lanrong,Zhao, Ming,Gu, Keli,Wang, Chao,Ju, Jingfang,Peng, Shiqi
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p. 1764 - 1774
(2008/09/20)
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- Toward the development of chemoprevention agents. Part 1: Design, synthesis, and anti-inflammatory activities of a new class of 2,5-disubstituted-dioxacycloalkanes
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A new class of 2,5-disubstituted-dioxacycloalkanes were designed and synthesized via stereoselective synthetic method as cancer chemoprevention agents. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Some of these compounds exhibited comparable or better anti-inflammatory activities than that of aspirin suggesting that they can be further developed as potential anti-inflammatory drug lead compounds. In addition, treatment of these anti-inflammatory agents did not prolong tail bleeding time in mice. The structure/activity relationships were also analyzed among these compounds.
- Gu, Keli,Bi, Lanrong,Zhao, Ming,Wang, Chao,Ju, Jingfang,Peng, Shiqi
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p. 4775 - 4799
(2008/03/14)
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- Toward the development of chemoprevention agents. Part II: Chemo-enzymatic synthesis and anti-inflammatory activities of a new class of 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes
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A new series of optically pure 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes were designed and synthesized via a chemo-enzymatic combined method to develop new chemoprevention agents. Twenty-four of newly synthesized compounds significantly inhibited xylene-induced rat ear edema and exhibited comparable or better anti-inflammatory activities than the reference drug aspirin. Treatment of these anti-inflammatory agents did not prolong the tail bleeding time in rat. In addition, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes exhibited good membrane permeability based on in vitro Caco-2 cell monolayer permeability assay. Furthermore, some preliminary structure-activity relationships were further analyzed among these compounds. Taken together, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes may represent a new class of anti-inflammatory drugs with safer pharmacological profile.
- Gu, Keli,Bi, Lanrong,Zhao, Ming,Wang, Chao,Ju, Jingfang,Peng, Shiqi
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p. 6273 - 6290
(2008/04/05)
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- Total synthesis of lysobactin
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Antibiotic resistance has become a significant public health concern. Antibiotics that belong to new structural classes and manifest their biological activity via novel mechanisms are urgently needed. Lysobactin, a depsipeptide antibiotic has displayed very strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as vancomycin-resistant enterococci (VRE) with minimum inhibitory concentrations (MICs) ranging from 0.39 to 0.78 μg/mL. The MIC values against VRE were more than 50-fold lower than those reported for vancomycin itself. Lysobactin was found to inhibit nascent peptidoglycan formation; however, this activity was not antagonized in the presence of N-acyl-L-Lys-D-Ala-D-Ala, the binding domain on the cell wall precursors that is utilized by vancomycin. Thus, lysobactin represents a promising agent for the treatment bacterial infections due to resistant pathogens. We describe a convergent synthesis of lysobactin that relies upon a highly efficient macrocyclization reaction to assemble the 28-membered cyclic depsipeptide. This synthesis provides the foundation for further study of the mode of action utilized by lysobactin and its analogues.
- Guzman-Martinez, Aikomari,Lamer, Ryan,VanNieuwenhze, Michael S.
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p. 6017 - 6021
(2008/02/04)
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- Synthesis of α-amino acids by reaction of aziridine-2-carboxylic acids with carbon nucleophiles
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A variety of homochiral α-amino acids have been prepared in good yield via regioselective reaction of higher order cuprates with (2S)-N-para-toluenesulfonylaziridine-2-carboxylic acid 4. The reaction was much less regioselective and low yielding when higher order cuprates were reacted with the more hindered aziridine carboxylic acid 30, the principal products being protected β-amino acids. Reaction of lithium trimethylsilylacetylide with the aziridine acid 30, however, gave a protected α-amino acid which was converted to the protected isoleucine ester 37. The Royal Society of Chemistry 2006.
- Beresford, Kenneth J. M.,Church, Nicola J.,Young, Douglas W.
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p. 2888 - 2897
(2008/02/08)
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- Ultrasound accelerated synthesis of proteinogenic and α,α- dialkylamino acid ester salts
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A simple and efficient sonochemical esterification of proteinogenic as well as cyclic α,α-dialkyl amino acid methyl and ethyl ester hydrochloride salts employing thionyl chloride and alcohol has been reported. All the amino acid esters made have been obtained in good yield (94-98%) as pure compounds.
- Kantharaju,Babu, Vommina V. Suresh
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p. 1942 - 1944
(2007/10/03)
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- Preparation of amino acid amides
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A process for making amino acid amides, comprising reacting an amino acid, or acid salt of an amino acid, with a halogenating agent, or with a substance that reacts with carboxylic acids to form a leaving group, to form an intermediate, then reacting the intermediate with ammonia. When the amino acid or acid salt is enantiomerically pure, the amide will be a stereoisomer. An amide made by the process can be used to form levetiracetam.
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Page/Page column 2
(2008/06/13)
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- Synthesis of erythro-α-Amino β-hydroxy Carboxylic Acid Esters by Diastereoselective Photocycloaddition of 5-Methoxyoxazoles with Aldehydes
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A new photoaldol route to α-amino-β-hydroxy carboxylic acid esters is initiated by the photocycloaddition of aromatic or aliphatic aldehydes to 5-methoxyoxazoles. The 4-unsubstituted 5-methyloxazole 1 gave the cycloadducts 8a-f in high yields and excellent exo-diastereoselectivities. Hydrolysis of 8a-f gives the N-acetyl α-amino-β-hydroxy esters 9a-f, which could be subsequently converted into the corresponding Z-didehydro α-amino acids 10a-f. Quartenary α-amino-β-hydroxy esters 12, 14, 16, 18, and 20, which are stable against dehydration, were obtained from the 4-alkylated 5-methoxyoxazoles 2-6, in most cases highly erythro-selective due to the high degree of stereocontrol (exo) at the photocycloaddition (to give 11, 13, 15, 17, and 19) level. The relative configurations of the N-acetyl α-amino-β-hydroxy esters were determined by NMR spectroscopy and comparison with chiral pool-derived compounds as well as by X-ray structure determination of the ester 23, formed by hydrolysis of the cycloadduct 22, derived from photocycloaddition of propionaldehyde to the isoleucine-derived oxazole 21.
- Griesbeck, Axel G.,Bondock, Samir,Lex, Johann
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p. 9899 - 9906
(2007/10/03)
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- Benzo[A] [phenazin-11-carboxamide derivatives and their use as joint inhibitors of topomerase I and II
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A compound which is a benzo[a]phenazine-11-carboxamide derivative of formula (I) wherein each of R1 to R4, which are the same or different, is selected from hydrogen, halogen, hydroxyl, C1-C6 alkoxy which is unsubstituted or substituted, heteroaryloxy, C1-C6 alkyl which is unsubstituted or substituted, nitro, cyano, azido, amidoxime, CO2R10, CON(R12)2, OCON(R12), SR10, SOR11, SO2(R11), SO2N(R12)2, N(R12)2, NR10SO2R11, N(SO2R11)2NR10(CH2)nCN, NR10COR11, OCOR11 or COR10; each of R5 to R7, which are the same or different, is selected from hydrogen, halogen, hydroxy, C1-C6 alkoxy, C1-C6 alkyl, SR10 and N(R12)2; Q is C1-C6 alkylene which is unsubstituted or substituted by (i) C1-C6 alkyl which is unsubstituted or substituted, (ii) hydroxy, provided that the hydroxy group is not, to either of the N atoms adjacent to Q in formula (I), (iii) CO2R10, or (iv) CON(R12); R1 and R9, which are the same or different, are each hydrogen or C1-C6 alkyl, or R8 and R9 together with the nitrogen atom to which they are attached form a saturated 5- or 6-membered N-containing heterocyclic ring which may include one additional heteroatom selected from O, N and S, or one of R8 and R9 is an alkylene chain optionally interrupted by O, N or S, which is attached to a carbon atom on the alkylene chain represented by Q to complete a saturated 5- or 6-membered N-containing heterocyclic ring as defined above; or a pharmaceutically acceptable salt thereof; with the proviso that at least one R1 to R4 is other than hydrogen. These compounds are inhibitors of topoisomerase I and/or topoisomerase II and can be used to treat tumours, including tumours which express MDR.
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- Enantioselective Lewis Acid-Catalyzed Mukaiyama-Michael Reactions of Acyclic Enones. Catalysis by allo-Threonine-Derived Oxazaborolidinones
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allo-Threonine-derived O-aroyl-B-phenyl-N-tosyl-1,3,2 -oxazaborolidin-5-ones 1g,n catalyze the asymmetric Mukaiyama-Michael reaction of acyclic enones with a trimethylsilyl ketene S,O-acetal in high enantioselectivity. A range of alkenyl methyl ketones is successfully employed as Michael acceptors affording ee values of 85-90% by using 10 mol % of the catalyst. The use of 2,6-diisopropylphenol and tert-butyl methyl ether as additives is found to be essential to achieve high enantioselectivity in these reactions. The effects of the additives are discussed in terms of the retardation of an Si+-catalyzed racemic pathway, which seriously deteriorates the enantioselectivity of asymmetric Mukaiyama-Michael reactions. A working model for asymmetric induction is proposed based on correlation between catalyst structures and enantioselectivities.
- Wang, Xiaowei,Adachi, Shinya,Iwai, Hiroyoshi,Takatsuki, Hiroshi,Fujita, Katsuhiro,Kubo, Mikako,Oku, Akira,Harada, Toshiro
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p. 10046 - 10057
(2007/10/03)
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- Processes for producing β-halogeno-α-amino-carboxylic acids and phenylcysteine derivatives and intermediates thereof
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An industrially advantageous method of producing β-halogeno-α-aminocarboxylic acids is provided. Methods are also provided of producing optically active N-protected-S-phenylcysteines having high optical purity and of intermediates thereof, respectively, in which the above production method is utilized. A method of producing β-halogeno-α-aminocarboxylic acids or salts thereof is disclosed which comprises halogenating the hydroxyl group of a β-hydroxy-α-aminocarboxylic acid (in which the basicity of the amino group in α-position is not masked by the presence of a substituent on said amino group) or a salt thereof with an acid with a halogenating agent. A method of producing optically active N-protected-S-phenylcysteines represented by the general formula (3) or salts thereof is further disclosed which comprises applying the above production method to optically active serine or a salt thereof and then carrying out treatment with an amino-protecting agent and reaction with thiophenol under a basic condition.
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Page column 16
(2010/01/31)
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- Serine and threonine β-lactones: A new class of hepatitis A virus 3C cysteine proteinase inhibitors
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Hepatitis A virus (HAV) 3C enzyme is a cysteine proteinase essential for viral replication and infectivity and represents a target for the development of antiviral drugs. A number of serine and threonine β-lactones were synthesized and tested against HAV 3C proteinase. The D-N-Cbz-serine β-lactone 5a displays competitive reversible inhibition with a Ki value of 1.50 × 10-6 M. Its enantiomer, L-N-Cbz-serine β-lactone 5b is an irreversible inactivator with kinact = 0.70 min-1, KI = 1.84 × 10-4 M and kinact/KI = 3800 M-1 min-1. Mass spectrometry and HMQC NMR studies using 13C-labeled 5b show that inactivation of the enzyme occurs by nucleophilic attack of the cysteine thiol (Cys-172) at the β-position of the oxetanone ring. Although the N-Cbz-serine β-lactones 5a and 5b display potent inhibition, other related analogues with an N-Cbz side chain, such as the five-membered ring homoserine γ-lactones 14a and 14b, the four-membered ring β-lactam 33, 2-methylene oxetane 34, cyclobutanone 36, and 3-azetidinone 39, fail to give significant inhibition of HAV 3C proteinase, thus demonstrating the importance of the β-lactone ring for binding.
- Lall, Manjinder S.,Ramtohul, Yeeman K.,James, Michael N.G.,Vederas, John C.
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p. 1536 - 1547
(2007/10/03)
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- beta -thiopropionyl-aminoacid derivatives and their use as beta -lactamase inhibitors
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PCT No. PCT/EP97/00516 Sec. 371 Date Jan. 13, 1999 Sec. 102(e) Date Jan. 13, 1999 PCT Filed Feb. 3, 1997 PCT Pub. No. WO97/30027 PCT Pub. Date Aug. 21, 1997A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a beta -lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R1 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C1-6)alkylcarbonyloxy, (C1-6)alkoxycarbonyl, formyl or (C1-6)alkylcarbonyl group, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl(C1-6)alkyl, heterocyclyl or heterocyclyl(C1-6)alkyl; R2 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl; R3 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms, (C3-7)cycloalkyl, fused aryl(C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl-(CHR10)m-X-(CHR11)n, heterocyclyl or heterocyclyl-(CHR10)m-X-(CHR11)n, where m is 0 to 3, n is 1 to 3, each R10 and R11 is independently hydrogen or (C1-4)alkyl and X is O, S(O)x where x is 0-2, or a bond; R4 is hydrogen, or an in vivo hydrolysable acyl group; and R5 and R6 are independently hydrogen and (C1-6)alkyl or together represent (CH2)p where p is 2 to 5. Some compounds are claimed per se.
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- A facile synthesis of enantiomerically pure 1-(piperazin-2-yl)ethan-1-ol derivatives from (2s,3r)-threonine
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Starting from the proteinogenic amino acid (2S,3R)-threonine (4) a novel method for the preparation of enantiomerically pure 1-(1-benzylpiperazin-2- yl)ethan-1-ols with various substituents in position 4 (15 - 20) is described. The sequence involves as key step the LiAlH4 reduction of the bicyclic piperazinediones 11a,b-14a,b which establishes the 1-benzyl protective group and simultaneously liberates the 1-hydroxyethyl side chain for further transformations.
- Soukara, Stella,Wuensch, Bernhard
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p. 1739 - 1746
(2007/10/03)
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- Synthesis of Dolastatin I, a cytotoxic cyclic hexapeptide from the sea hare Dolabella auricularia
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Dolastatin I, a cytotoxic cyclic hexapeptide isolated from the Japanese sea hare Dolabella auricularia, was enantioselectively synthesized, which confirmed its stereostructure.
- Kigoshi, Hideo,Yamada, Shiho
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p. 12301 - 12308
(2007/10/03)
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