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A novel preparation of (+)-methyl pederate (4), a key intermediate in syntheses of mycalamides (1), marine natural products from a New Zeland sponge of the genus Mycale, is described. The key step involves palladium- catalyzed intramolecular allylic alkylation of the carbonate 21, derived from (+)-(4R,5R,E)-5-(tert-butyldimethylsiloxy)-4-methyl-2-hexenol (13), yielding lactones 5 in 87% yield. Demethoxycarbonylation of the cyclization products 5 and further functional group transformations led to (+)-methyl pederate (4).

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Oxazolidine – Wikipedia,
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A short, convergent and general strategy for stereoselective total synthesis of biologically active alpha-substituted gamma-hydroxymethyl gamma-lactone based natural products cananginone C and debilisone A has been developed. The salient features of this synthesis include Cadiot-Chodkiewicz coupling, Evans allylation, Sharpless asymmetric dihydroxylation and gamma-lactonization. The originally proposed structure of debilisone A has been revised.

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Studies on the alkylation of enolates derived from a range of N-acyl-5,5-dimethyloxazolidin-2-ones and N-acyl-5,5-diphenyloxazolidin-2-ones reveal that high yields and high diastereoselectivities are best obtained when homochiral 4-isopropyl-5,5-dimethyloxazolidin-2-one is employed as a chiral auxiliary.

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An isoquinuclidine derivative represented by the following general formula (I): (I) [wherein A1 is methylene or carbonyl]: R1 is hydrogen or methyl: R2 is -(CH2)n-A2-Ph (n is an integer of 0 to 3 and A2 is a single bond or -O-): and R3 is -COOH, -COOR4, -COSR4 (R4 is lower alkyl, unsubstituted phenyl, or phenyl substituted by a lower alkyl, lower alkoxy, hydroxyl, methoxycarbonyl, ethoxycarbonyl, or trifluoromethanesulfonamide group or by a halogen atom), etc.] or a pharmaceutically acceptable salt of the compound. Also provided is an oral remedy for diabetes, which contains the compound and has hypoglycemic activity.

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A highly efficient, two-step, one-pot synthetic strategy for amides and peptides was developed by employing ynamides as novel coupling reagents under extremely mild reaction conditions. The ynamides not only are effective for simple amide and dipeptide synthesis but can also be used for peptide segment condensation. Importantly, no racemization was detected during the activation of chiral carboxylic acids. Excellent amidation selectivity toward amino groups in the presence of -OH, -SH, -CONH2, ArNH2, and the NH of indole was observed, making the protection of these functional groups unnecessary in amide and peptide synthesis.

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Compounds of the general formula (I) in which the meanings of the substituents R1 and R2 are as stated in claim 1, have renin-inhibiting properties and can be used as medicines.

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Abstract The asymmetric total synthesis of marine polypropionate natural products siphonarienal and siphonarienone has been achieved from a common precursor 3. The key transformations of this synthesis are the diastereoselective oxidative kinetic resolution, Wittig olefination, Grignard reaction, and Evans asymmetric alkylation for the installation of a third stereogenic center of the target molecules from commercially available starting materials.

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Previous reports from our laboratories described potent tripeptide thrombin inhibitors which incorporate heterocycle-substituted chlorophenyl groups in the P1 position. Using these as lead compounds for further optimization, we identified sites of metabolism and designed analogs with 4-fluoroproline in P2 and cyclopropane-containing side chains in P3 as an approach to reducing metabolism and improving their oral pharmacokinetic performance. The large (300-fold) difference in potency between analogs containing (4R)- and (4S)-4-fluoroproline was rationalized by analyzing inhibitor-enzyme interactions in crystal structures of related compounds and by molecular modeling which indicated that the more potent (4R)-4-fluoroproline isomer stabilizes a proline ring conformation that is preferred for binding to the enzyme. An optimal compound from this work, 41, exhibits high potency in a coagulation assay in human plasma (2×APTT = 190 nM), excellent selectivity versus the digestive enzyme trypsin (Ki = 3300 nM), and excellent oral bioavailability in dogs with moderate clearance (F = 100%, CL = 12 mL/min/kg).

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The reaction of cyclic thioimidates with active methylene compounds in the presence of acetic acid anhydride was studied. In case of six- and seven-membered derivatives the reaction proceeded via substitution of thiomethoxy group affording cyclic enamines. In case of five-membered derivatives the reaction proceeded via opening of the thioimidate ring affording functionalized aminopropane derivatives.

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An easily assembled catalyst from (±)-BINOL (1,1?-bi-naphthol) and Zr(OiPr)4·iPrOH selectively reduces aldehydes at room temperature. Ketones remain intact under these conditions. A catalytic amount of BINOL-Zr complex in the presence of 2-propanol also effectively reduces a variety of chiral and achiral aldehydes.

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