- Synthesis of hydroxymethyl side-chained α-aminoxy diamide
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Unnatural polar α-aminoxy acid residue with proteingenous hydroxymethyl side chain, a building block of the peptidomimetic foldamer of -aminoxy peptide, was synthesized starting from natural amino acid L-serine. The starting material, L-serine, undergoes a reaction sequence to produce compound 1 in three steps: (1) the neighboring carboxyl group participates in diazotization/bromination to transform the amino group to a bromo group, (2) the C-terminal carboxyl group is protected, and (3) bromide is SN2-displaced by N-hydroxyl phthalimide to introduce a N-O bond. After several conventional deprotection/coupling reactions, compound 1 is easily transformed to an -aminoxy diamide, which can be widely used in peptidomimetics design.
- Luo, Zheng,Yang, Hai-Feng,Chang, Xiao-Wei,Zhang, Dan-Wei
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Read Online
- Introduction of chirality into PNA by replacement of the achiral methylene carbonyl linkage to the nucleobase
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A novel approach to the introduction of chirality into peptide nucleic acid (PNA) by replacement of the methylene carbonyl linker by an alpha-amino acid derived moiety is described. A monomer compatible with Fmoc-based oligomerization chemistry possessing an L-serine derived linker has been synthesized and incorporated into PNA oligomers. A single, central substitution in a hexathymine PNA strongly destabilized triple helix formation whereas a central substitution in a mixed sequence is much better tolerated. We have investigated the influence of this substitution on the selectivity for strand composition (DNA versus RNA complement) and strand orientation (antiparallel versus parallel) in the context of duplex formation. A PNA 11-mer with a single substitution demonstrates a preference for an antiparallel RNA complement, as judged by thermal denaturation analysis of the complexes. Copyright Taylor & Francis Group, LLC.
- Wojciechowski, Filip,Hudson, Robert H. E.
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Read Online
- Quinoline derivative having indoleamine-2,3-dioxygenase inhibitory activity
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The present invention provides a quinoline derivative having indoleamine-2,3-dioxygenase inhibitory activity, specifically a compound represented by a general formula (I) or a pharmaceutically acceptable salt thereof, a pharmaceutical composition and a pr
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Paragraph 0442-0444
(2020/04/17)
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- SELECTIVE INHIBITORS OF NLRP3 INFLAMMASOME
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The present disclosure relates to compounds of Formula (I): (I); and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as autoinflammatory and autoimmune diseases and cancers.
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Paragraph 0573
(2019/02/15)
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- Synthesis of Functionalized N-Acetyl Muramic Acids to Probe Bacterial Cell Wall Recycling and Biosynthesis
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Uridine diphosphate N-acetyl muramic acid (UDP NAM) is a critical intermediate in bacterial peptidoglycan (PG) biosynthesis. As the primary source of muramic acid that shapes the PG backbone, modifications installed at the UDP NAM intermediate can be used to selectively tag and manipulate this polymer via metabolic incorporation. However, synthetic and purification strategies to access large quantities of these PG building blocks, as well as their derivatives, are challenging. A robust chemoenzymatic synthesis was developed using an expanded NAM library to produce a variety of 2-N-functionalized UDP NAMs. In addition, a synthetic strategy to access bio-orthogonal 3-lactic acid NAM derivatives was developed. The chemoenzymatic UDP synthesis revealed that the bacterial cell wall recycling enzymes MurNAc/GlcNAc anomeric kinase (AmgK) and NAM α-1 phosphate uridylyl transferase (MurU) were permissive to permutations at the two and three positions of the sugar donor. We further explored the utility of these derivatives in the fluorescent labeling of both Gram (-) and Gram (+) PG in whole cells using a variety of bio-orthogonal chemistries including the tetrazine ligation. This report allows for rapid and scalable access to a variety of functionalized NAMs and UDP NAMs, which now can be used in tandem with other complementary bio-orthogonal labeling strategies to address fundamental questions surrounding PG's role in immunology and microbiology.
- Demeester, Kristen E.,Liang, Hai,Jensen, Matthew R.,Jones, Zachary S.,D'Ambrosio, Elizabeth A.,Scinto, Samuel L.,Zhou, Junhui,Grimes, Catherine L.
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supporting information
p. 9458 - 9465
(2018/07/21)
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- Intermolecular Carboamination of Unactivated Alkenes
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Herein, we report the first example of group transfer radical addition of O-vinylhydroxylamine derivatives onto unactivated alkenes. By utilizing O-vinylhydroxylamine derivatives as both the N- and C-donors, this reaction enables intermolecular carboamination of unactivated alkenes in an atom economical fashion. As the process is initiated through N-radical addition followed by C-transfer, linear carboamination products are afforded. This differs from canonical radical carbofunctionalization of olefins, which typically favors branched product owing to initiation by C-radical addition.
- Zhang, Yu,Liu, Haidong,Tang, Luning,Tang, Hai-Jun,Wang, Lu,Zhu, Chuan,Feng, Chao
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supporting information
p. 10695 - 10699
(2018/09/06)
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- NOVEL CYCLIC DEPSIPEPTIDE DERIVATIVES AND HARMFUL ORGANISM CONTROL AGENTS COMPRISING THE SAME
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An objective of the present invention is to provide novel cyclic depsipeptide derivatives and harmful organism control agents including the same as each other. Specifically, the present invention provides compounds represented by formula (1) or stereoisom
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Paragraph 0305; 0306; 0307; 0308
(2017/08/26)
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- The asymmetric total synthesis of (+)-salvianolic acid A
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An asymmetric synthesis of (+)-salvianolic acid A with cardioprotective properties, has been accomplished in a convergent manner in eight steps and 10.6% overall yield. This synthesis features an asymmetric addition of organometallics to optically pure 2,3-epoxypropionate in the presence of BF3·Et2O, Ru(III)-catalyzed directed [Formula presented] olefination, and I2-catalyzed isomerization reaction.
- Zheng, Yong,Song, Wei-Bin,Xuan, Li-Jiang
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supporting information
p. 5047 - 5050
(2016/07/25)
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- CYCLIC DEPSIPEPTIDE DERIVATIVES AND PEST CONTROL AGENTS COMPRISING THE SAME
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There are provided compounds represented by formula (1), which are novel cyclic depsipeptide derivatives, or stereoisomers thereof, and pest control agents including the same.
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Paragraph 0215
(2017/03/25)
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- Pyrazolopyrimidine derivative, preparation method, pharmaceutical composition and application
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The invention discloses a pyrazolopyrimidine derivative, a preparation method, a pharmaceutical composition and application. The invention provides the pyrazolopyrimidine derivative as shown in a formula I and stereoisomer or solvate or pharmaceutically acceptable salts or active metabolite or prodrug thereof. The pyrazolopyrimidine derivative as shown in the formula I has good inhibitory activity on Bruton's tyrosine kinase (Btk) and particularly has good in vitro and in vivo inhibitory activity on growth of tumor cells, and a good marketization prospect is achieved. Please see the formula I in the description.
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Paragraph 0304; 0305; 0306
(2017/07/19)
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- Total Synthesis of Solandelactone i
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Since the marine natural products solandelactones A-I were isolated from the hydroid Solanderia secunda and investigated by Seo et al. in 1996, considerable synthetic efforts toward these marine oxylipins followed. However, the structure elucidation of solandelactone I remained incomplete, and no synthesis has been reported. On the basis of our retrosynthetic analysis, the key building blocks were combined in a Horner-Wadsworth-Emmons reaction to create two common intermediates for the stereodivergent synthesis of all four diastereomers 1-4 matching the proposed structure of solandelactone I. Comparison of the published analytical data of natural product solandelactone I and data obtained from the synthetic endeavor toward diastereomers 1-4 enabled the structure assignment of isomer 3; the proposed biosynthetic pathway for marine oxylipins also supports the result.
- Eichenauer, Nils C.,Tschersich, Roxanne,Pietruszka, J?rg
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supporting information
p. 2782 - 2790
(2015/12/09)
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- NOVEL CYCLIC DEPSIPEPTIDE DERIVATIVE AND PEST CONTROL AGENT COMPRISING SAME
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An objective of the present invention is to provide novel cyclic depsipeptide derivatives and harmful organism control agents including the same as each other. Specifically, the present invention provides compounds represented by formula (1) or stereoisom
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Paragraph 0374-0376
(2017/09/14)
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- PROCESS FOR PREPARATION OF LACOSAMIDE AND SOME N-BENZYL-PROPANAMIDE INTERMEDIATE DERIVATIVES
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The present invention discloses novel process for the preparation of (2R)-2-acetamido-N- benzyl-3-methoxypropanamide of Formula I involving novel intermediates of Formula - XIX and Formula - XX.
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Page/Page column 16
(2012/02/13)
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- METHODS AND MATERIALS FOR PREPARING ORGANIC COMPOUNDS FROM PRIMARY AMINES
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Methods are disclosed for the conversion of primary amines to other functional groups. The methods can be used to prepare chiral organic compounds, including organic alcohols and organic halides. The methods can be carried out by treating a primary amine with an activating agent and a nitrosyl agent to produce the transformed compound along with nitrous oxide.
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Page/Page column 24-27
(2008/06/13)
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- Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters
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The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide α,β-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 μM), the ketomethylene isosteres and tripeptide α,β-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 μM). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 μM is obtained by condensation of the Phe-Phe dipeptide α,β-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 μM.
- Shie, Jiun-Jie,Fang, Jim-Min,Kuo, Tun-Hsun,Kuo, Chih-Jung,Liang, Po-Huang,Huang, Hung-Jyun,Wu, Yin-Ta,Jan, Jia-Tsrong,Cheng, Yih-Shyun E.,Wong, Chi-Huey
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p. 5240 - 5252
(2007/10/03)
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- Synthesis of optically active N6-alkyl derivatives of (R)-3-(adenin-9-yl)-2-hydroxypropanoic acid and related compounds
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Reaction of ethyl (R)-oxiranecarboxylate (2a) with various nucleobases (adenine, 6-chloropurine, thymine, cytosine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one and 4-methoxypyrimidin-2(1H)-one) afforded ethyl 3-substituted-2-hydroxypropanoates 4-10. Enantioselectivity of this reaction is dependent on the type of the base: 6-chloropurine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one, thymine and cytosine gave optically pure R enantiomers. In other cases, partial or complete racemization occurred. Optically pure ethyl (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoate (5a) was hydrolyzed to give (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoic acid (11). Reactions of 11 with various primary or secondary amines led to N6-substituted (R)-3-(adenin-9-yl)-2-hydroxypropanoic acids 14-19. Enantiomeric purity was determined from 1H NMR spectra measured in the presence of (-)-(R)-1-(9-anthryl)-2,2,2-trifluoroethan-1-ol.
- Krecmerova, Marcela,Budesinsky, Milos,Masojidkova, Milena,Holy, Antonin
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p. 931 - 950
(2007/10/03)
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- An improved strategy for the stereoselective synthesis of glycosides using glycosidases as catalysts
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An alternative strategy for the synthesis of glycosides, using glycosidase enzymes, has been developed. In contrast to previous procedures, this new method uses limiting amounts of the acceptor alcohol substrate in combination with an excess of the glycos
- Baker,Turner,Webberley
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p. 2517 - 2522
(2007/10/02)
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- Neuromuscular blocking agents. Some approaches to short acting compounds
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A series of amidic and N-methylamidic methyl and trideuteromethyl quaternary analogues of atracurium have been prepared.All were less potent and longer acting neuromuscular blocking agents than atracurium, and all showed appreciable vagal blockade at neur
- Stenlake, J B,Dhar, N C,Haddow, J,McDonald, I M,Maehr, R B,Wastila, W B
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p. 463 - 477
(2007/10/02)
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- Preparation d'α-hydroxyesters et d'α-hydroxyaldehydes enantiomeriquement purs. Application a la synthese enantiospecifique de la pheromone sexuelle de la cochenille Pseudococcus comstocki
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Enantiomerically pure glycidic esters may be obtained in good yields by nitrous deamination of (S) or (R) serine; 2-bromo-3-hydroxy propionic acid is obtained and cyclized with alcoholic potash to give potassium glycidate; by reacting this salt with a sulfate, a primary iodide or an active bromide in acetonitrile in the presence of 18-crown-6, various glycidic esters were prepared.The ethyl glycidate reacts with lithiocuprates (alkyl or vinyl) but also with magnesiocuprates to afford a totally regiospecific reaction with the exclusive formation of α-hydroxyesters.The reaction is also possible with acetylides but it is necessary to use aluminium acetylides.With organolithium compounds reaction with the ester function of methyl glycidate occurs, leading to the formation of α-epoxyketones.The reduction of α-hydroxyesters (as protected form) with DIBAL-H at -70 deg C affords the corresponding α-hydroxyaldehydes in nearly quantitative yields.These reactions were applied to the synthesis of (R)-(+)-2,6-dimethyl-1,5-heptadien-3-ol acetate, the sex pheromone of the Comstock Mealybug, Pseudococcus comstocki.
- Larcheveque, Marc,Petit, Yves
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p. 130 - 139
(2007/10/02)
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- 104. Bromination of Cyclic Acetals from α-Amino Acids and α- or β-Hydroxy Acids with N-Bromosuccinimide
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The preparation of novel electrophylic building blocks for the synthesis of enantiomerically pure compounds (EPC) is described.Thus, the 2-(tert-butyl)dioxolanones, -oxazolidinones, -imidazolidinones, and -dioxanones obtained by acetalization of pivalalde
- Zimmermann, Juerg,Seebach, Dieter
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p. 1104 - 1114
(2007/10/02)
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- A SIMPLE PREPARATION OF R OR S GLYCIDIC ESTERS; APPLICATION TO THE SYNTHESIS OF ENANTIOMERICALLY PURE α-HYDROXYESTERS
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The simple preparation of enantiomerically pure α-hydroxyesters by the regioselective reaction of lithio and magnesiocuprates with glycidic esters 3 or 3' readily available from serine is described.
- Larcheveque, Marc,Petit, Yves
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p. 1993 - 1996
(2007/10/02)
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