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Stereoselective synthesis of the C18-C34 fragment of antascomicin A is described. Construction of the C27-C34 carbocycle moiety was achieved via catalytic Ferrier carbocylization and Johnson-Claisen rearrangement, which was converted to iodide 2 by use of asymmetric alkylation and Sharpless epoxidation as key transformations. Coupling of iodide 2 and sulfone 3 furnished the C18-C34 fragment.

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Oxazolidine – Wikipedia,
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Highly selective asymmetric synthesis of 2-hydroxy fatty acid methyl esters has been accomplished through chiral imide enolates. Five chiral oleic acid imides were prepared by reaction of oleic acid with pivaloyl chloride followed by reaction with five different lithiated chiral oxazolidinones including (R)-(+)-4-benzyl-2-, (S)-(-)-4-benzyl-2-, (4R, 5S)-(+)-4-methyl-5-phenyl-2-, (4S, SR)-(-)-4-methyl-5-phenyl-2-, and (R)-(+)-4-isopropyl-2-oxazolidinones in 88-92% yields. The chiral imides were reacted with NaN(Me3Si)2 at -78C to give enolates, which subsequently reacted with 2-(phenylsulfonyl)-3-phenyloxaziridine to give hydroxylated products in 78-83% yields. Methanolysis of the hydroxylated products with magnesium methoxide gave methyl 2-hydroxyoleate. Enantiomeric excesses (ee) of the products were determined to be very high (98-99% ee) by 1H nuclear magnetic resonance study after esterification of the hydroxy group with (S)-(+)-O-acetylmandelic acid. Enantioselective hydroxylation of other fatty acids including elaidic, petroselinic, vaccenic, and linoleic was evaluated under the similar conditions using (4R, 5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone as a chiral auxiliary to give 98% ee values for all cases.

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Catalysts are substances that increase the reaction rate of a chemical reaction without being consumed in the process. A catalyst does not appear in the overall stoichiometry of the reaction it catalyzes. You can also check out more blogs about 102029-44-7Related Products of 102029-44-7

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This invention is directed to compounds of formula I: STR1 wherein the variables are as described herein. Compounds within the scope of the present invention possess useful properties, more particularly pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. Compounds within the scope of the present invention may also inhibit an MMP, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting MMPs, such disease states involve tissue breakdown and those associated with a physiologically detrimental excess of TNF. The present invention is therefore also directed to the pharmaceutical use of the compounds, pharmaceutical compositions containing the compounds, intermediates leading thereto and methods for the preparation of the compounds and their intermediates.

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Cortisol homeostasis has been linked to the pathogenesis of metabolic syndrome (MetS), since it stimulates hepatic gluconeogenesis and adipogenesis. MetS is classified as a constellation of health conditions that increase the risk of type 2 diabetes and cardiovascular disease. Intracellular cortisol levels are regulated by 11beta-hydroxysteroid dehydrogenase (type 1 and type 2) in a tissue dependent manner. The type 1 enzyme (11beta-HSD1) is widely expressed in glucocorticoid targeted tissues and is responsible for the conversion of cortisone to the active cortisol. Local reduction of cortisol regeneration presents a potential strategy for MetS treatment. Recently we disclosed the total synthesis of (+)-colletoic acid as a potent 11beta-HSD1 inhibitor. Herein, we describe our improved processing chemistry for the synthesis of the colletoic acid core to access a diverse number of derivatives for evaluation against 11beta-HSD1. The Evan’s chiral auxiliary was utilized to construct the acyclic precursor 12 to afford the acorane core 9 using a modified Heck reaction in excellent chemical yields. The colletoic acid core derivatives showed modest activity against 11beta-HSD1 and will serve for further biological evaluation.

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In an effort to find answers to the tantalizing questions about the absolute configurations of a group of long-known natural phenylpropanoids with very similar structures but different signs for the optical rotations, the compounds in question were synthesized in enantiomerically pure form using Evans asymmetric alkylation to generate the stereogenic centres with predefined absolute configurations. The 1H and 13C NMR spectra of the synthetic products were very consistent with those reported for their natural counterparts. In most cases, the optical rotations were also consistent with the corresponding data for the natural samples. The new findings not only allowed unequivocal assignments of the absolute configurations for the natural products, but also revealed that the configurations of closely related compounds from the same plant may be different. Copyright

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The present invention relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, where Ri, R2, R3, R4, R5, R6, R7, Rs and m are as defined herein, pharmaceutical compositions comprising these compounds and methods of use of these compounds for treating a TGR5 mediated disease or condition.

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A short efficient total synthesis of 10-deoxymethynolide (2c), the aglycon of 10-deoxymethymycin (1c), has been accomplished in 16 steps and 12% overall yield from (S)-3-O-p-toluenesulfonyl-3-hydroxy-2-methylpropanal (15c). The synthesis features an expeditious preparation of (+)-5a, a synthetic equivalent of the Prelog-Djerassi lactonic acid, and the construction of a 12-membered lactone through an intramolecular Nozaki- Hiyama-Kishi coupling reaction.

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Selective inhibition of FKBP51 has emerged as possible novel treatment for diseases like major depressive disorder, obesity, chronic pain, and certain cancers. The current FKBP51 inhibitors are rather large, flexible, and have to be further optimized. By using a structure-based rigidification strategy, we hereby report the design and synthesis of a novel promising bicyclic scaffold for FKBP51 ligands. The structure-activity analysis revealed the decalin scaffold as the best moiety for the selectivity-enabling subpocket of FBKP51. The resulting compounds retain high potency for FKBP51 and excellent selectivity over the close homologue FKBP52. With the cocrystal structure of an advanced ligand in this novel series, we show how the decalin locks the key selectivity-inducing cyclohexyl moiety of the ligand in a conformation typical for FKBP51-selective binding. The best compound 29 produces cell death in a HeLa-derived KB cell line, a cellular model of cervical adenocarcinoma, where FKBP51 is highly overexpressed. Our results show how FKBP51 inhibitors can be rigidified and extended while preserving FKBP51 selectivity. Such inhibitors might be novel tools in the treatment of human cancers with deregulated FKBP51.

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The present invention provides compounds of Formula (Ia): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

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The reaction of (S)-4-tosyloxymethyl-2-oxazolidinone, which was synthesized from (R)-glycidol through (R)-4-benzoyloxymethyl-2-oxazolidinone, with various lithium dialkylcuprate(I)s in THF proceeded smoothly to afford the corresponding protected amino alcohol derivatives in good yield.

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