- Total synthesis of (±)-leporin A
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An efficient synthesis of (±)-leporin A (1) has been developed using a tandem Knoevenagel condensation-inverse electron demand intramolecular hetero Diels-Alder reaction to construct the key tricyclic intermediate 3 from pyridone 5 and dienal 6 in one pot in 35% yield. Hydroxylation (71%) of 3 and methylation (77%) of the resulting hydroxypyridone 2 completed the first total synthesis of (±)-leporin A (1).
- Snider, Barry B.,Lu, Qing
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- Synthesis and antifungal activity of polycyclic pyridone derivatives with anti-hyphal and biofilm formation activity against Candida albicans
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Thirty-five pyridone derivatives were synthesized, with derivatization conducted on polycyclic pyridone scaffolds, including cis- or trans-oxydecalin and other cyclic structures, by domino-Knoevenagel-electrocyclic reactions. The anti-fungal activities of the synthesized compounds were tested against Candida albicans. Ten compounds inhibited hyphal formation without inhibiting growth. Pyridones with anti-hyphal formation activity (4c, 6d, 12a and 12c) were tested for their ability to inhibit biofilm formation. Compound 6d showed both anti-hyphal and biofilm inhibition activity.
- Kamauchi, Hitoshi,Kimura, Yu,Seki, Taishi,Sugita, Yoshiaki,Suzuki, Mitsuaki,Takao, Koichi,Ushiwatari, Mikoto
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- Practical Pd/C-catalysed suzuki-miyaura reactions for the preparation of 3-aryl-4-oxypyridin-2(1H)-ones, 3-aryl-2,4-oxypyridines and 3-aryl-2,4- oxyquinolines as useful intermediates for the synthesis of biologically active compounds
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Practical heterogeneous Pd/C-catalysed Suzuki-Miyaura cross-coupling reactions of 3-iodo-4-oxypyridin-2(1H)-ones, 3-iodo-2,4-oxypyridines, and 3-iodo-2,4-oxyquinolines with arylboronic acids are described as a useful and efficient alternative to homogeneous conditions. The methodology features ligand-free and environmentally friendly conditions, and tolerates a wide range of boronic acids. The cross-coupled products can be viewed as useful intermediates for the preparation of 3-aryl-4-hydroxypyridin-2(1H)-ones, which can be used as new nucleobases for antiherpetic agents.
- Lamblin, Marc,Bares, Hugo,Dessolin, Jean,Marty, Christel,Bourgougnon, Nathalie,Felpin, Francois-Xavier
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p. 5525 - 5533
(2012/10/29)
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- PYRIDONE GPR119 G PROTEIN-COUPLED RECEPTOR AGONISTS
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Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR 119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.
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Page/Page column 103
(2009/02/11)
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- Synthesis and evaluation of the antitumor agent TMC-69-6H and a focused library of analogs
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A concise, efficient and flexible total synthesis of the potent antitumor agent TMC-69-6H (2) is described. Key steps involve the palladium catalyzed regioselective addition of 4-hydroxy-2-pyridone 5 to pyranyl acetate 6 which is accompanied by a spontaneous 1,4-addition of the phenolic -OH group to the emerging enone to give the tricyclic product 7 in excellent yield. When this reaction is carried out with optically enriched (S)-6 (conveniently prepared by a lipase catalyzed kinetic dynamic resolution) in the presence of the chiral ligand (S,S)-12 and allylpalladium chloride dimer, the ensuing matched situation delivers the key building block (-)-7 in 96% ee. Its further elaboration into 2 involves a Julia-Kocienski olefination with tetrazolylsulfone 19 and a final N-oxidation effected by the peroxomolybdenum complex [(pyridine)MoO 5(HMPA)] to form the hydroxamic acid motif. The flexibility inherent to this route allows for the preparation of a focused library of analogues for biochemical evaluation. The results obtained show that N-hydroxy-2-pyridone derivatives constitute a promising new class of selective phosphatase inhibitors. In contrast to previous reports in the literature, however, TMC-69-6H and congeners are found to exhibit pronounced activities against the tyrosine protein phosphatase PTB1B, the dual specific phosphatase VHR, and the serine/threonine phosphatase PP1, while being only weak inhibitors for the dual specific phosphatases Cdc25 A and B. Two key intermediates of the synthesis route have been characterized by X-ray crystallography. Graphical Abstract.
- Fürstner, Alois,Feyen, Fabian,Prinz, Heino,Waldmann, Herbert
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p. 9543 - 9558
(2007/10/03)
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- Reactivity of Some 3-Substituted Derivatives of 2,6-Dihalogenopyridines Towards Potassium Amide in Liquid Ammonia .
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Reactions of 2,6-dichloro-3-phenyl-, 2,6-dibromo-3-phenyl-, 2,6-dichloro-3-dimethylamino- and 2,6-dibromo-3-dimethylaminopyridine with potassium amide in liquid ammonia were investigated.Whereas 2,6-dichloro-3-phenylpyridine yields 4-amino-2-benzylpyrimidine, from 2,6-dibromo-3-phenylpyridine as a product of a novel ring fission 2-amino-1-cyano-1-phenyl-but-1-en-3-yne was isolated, together with 4-amino-6-bromo-3-phenylpyridine and 2,6-diamino-3-phenylpyridine.It was shown that neither 2-amino-6-bromo-3-phenyl- nor 6-amino-2-bromo-3-phenylpyridine are intermediates in the formation of the 2,6-diamino derivative, as these bromo compounds are transformed in the basic medium into 1,3-dicyano-1-phenylpropene.From both 2,6-dichloro-3-dimethylamino- and 2,6-dibromo-3-dimethylaminopyridine mixtures are obtained from which only 2-amino-1-cyano-1-dimethylamino-but-1-en-3-yne and 4-amino-6-halogeno-3-dimethylaminopyridine were isolated.Mechanisms for the reactions studied are proposed, i.e. a SN(ANRORC) mechanism for the aminodebromination of 2,6-dibromo-3-phenylpyridine into the corresponding 2,6-diamino compound.
- Streef, J. W.,Hertog, H. J. den,Plas, H. C. van der
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p. 985 - 991
(2007/10/02)
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