- Overcoming the Deallylation Problem: Palladium(II)-Catalyzed Chemo-, Regio-, and Stereoselective Allylic Oxidation of Aryl Allyl Ether, Amine, and Amino Acids
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We report herein a Pd(II)/bis-sulfoxide-catalyzed intramolecular allylic C-H acetoxylation of aryl allyl ether, amine, and amino acids with the retention of a labile allyl moiety. Mechanistically, the reaction proceeds through a distinct double-bond isomerization from the allylic to the vinylic position followed by intramolecular carboxypalladation and the β-hydride elimination pathway. For the first time, C-H oxidation of N-allyl-protected amino acids to furnish five-membered heterocycles through 1,3-syn-addition is established with excellent diastereoselectivity.
- Begam, Hasina Mamataj,Jana, Ranjan,Manna, Kartic,Samanta, Krishanu
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supporting information
p. 7443 - 7449
(2020/10/09)
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- Macrocyclic Modulators of the Ghrelin Receptor
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The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.
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Paragraph 0574; 0575
(2018/05/03)
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- Synthesis of novel potent hepatitis C virus NS3 protease inhibitors: Discovery of 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a N-acyl-l-hydroxyproline bioisostere
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Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-l-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the P1-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a Ki value of 1.1 nM.
- Thorstensson, Fredrik,Wangsell, Fredrik,Kvarnstroem, Ingemar,Vrang, Lotta,Hamelink, Elizabeth,Jansson, Katarina,Hallberg, Anders,Rosenquist, Asa,Samuelsson, Bertil
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p. 827 - 838
(2007/10/03)
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- The Synthesis and Thymidylate Synthase Inhibitory Activity of L-γ-L-Linked Dipeptide and L-γ-Amide Analogues of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic Acid (ICI 198583)
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Sixteen γ-linked dipeptide and four L-Glu-γ-amide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) have beensynthesized and evaluated as inhibitors of thymidylate synthase (TS).Z-blocked L-Glu-γ-L-linked dipepti
- Bisset, Graham M. F.,Bavetsias, Vassilios,Thornton, Timothy J.,Pawelczak, Krzysztof,Calvert, A. Hilary,et al.
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p. 3294 - 3302
(2007/10/02)
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