- Highly enriched mixtures of methohexital stereoisomers by palladium-catalyzed allylation and their anaesthetic activity
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The stereoselective Pd-catalyzed allylation of MBA [5-(2′-hex-3′-yny1)-1-methylbarbituric acid] gives the commercial injection narcotic methohexital, which exists as four isomers: two diastereomeric pairs of enantiomers. The isomer composition produced depends on three stereochemical parameters: catalyst control, substrate control, and kinetic resolution. Judicious choice of these parameters allowed the synthesis of methohexital samples with greatly differing isomer compositions, and these samples were investigated with respect to their anaesthetic doses in rats. Some isomer compositions obtained were much more active than the commercially used drug and showed fewer side effects. As a consequence of the determination of the absolute configuration of the methohexital (SbRh) isomer, the unknown configuration of the trade product, the so-called α-racemate, can be established as (RbSh) and (SbRh). ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
- Brunner, Henri,Ittner, Karl-Peter,Lunz, Dirk,Schmatloch, Stefan,Schmidt, Thomas,Zabel, Manfred
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- Catalytic hydrogenation of aromatic amines at atmospheric pressure in water
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Rhodium on alumina (5% Rh) has been found to be a good catalyst for the hydrogenation of aromatic amines under atmospheric pressure at room temperature in water.
- Strotmann,Butenschon
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Read Online
- CYCLIC AMINE BASE-1 INHIBITORS HAVING A HETEROCYCLIC SUBSTITUENT
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Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is formula (I) X is -0-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24)(R25)or -SR35; R41 is alkyl, cycloalkyl, -S02(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula (I). Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.
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Page/Page column 46
(2008/06/13)
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- CYCLIC AMINE BACE-1 INHIBITORS HAVING A BENZAMIDE SUBSTITUENT
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Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R is-C(O)-N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer’s disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, and N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.
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Page/Page column 35
(2008/06/13)
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- Large scale synthesis of optically pure aziridines
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Disclosed is an efficient, inexpensive method for the preparation of chiral aziridines on a large scale.
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- Catalytic Hydrogenation of Chiral α-Amino and α-Hydroxy Esters at Room Temperature with Nishimura Catalyst without Racemization
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The hydrogenation of carboxylic acid derivatives at room temperature was investigated. With a mixed Rh/Pt oxide (Nishimura catalyst), low to medium activity was observed for various α-amino and α-hydroxy esters. At 100 bar hydrogen pressure and 10% catalysts loading, high yields of the desired amino alcohols and diols were obtained without racemization. The most suitable α-substituents were NH2, NHR, and OH, whereas β-NH2 were less effective. Usually, aromatic rings were also hydrogenated, but with the free bases of amino acids as substrates, some selectivity was observed. No reaction was found for α-NR2, α-OR, and unfunctionalized esters; acids and amides were also not reduced under these conditions. A working hypothesis for the mode of action of the catalyst is presented.
- Studer, Martin,Burkhardt, Stefan,Blaser, Hans-Ulrich
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p. 802 - 808
(2007/10/03)
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- Stereoselective intramolecular cyclization of allyl and homoallyl benzamide via π-allylpalladium complex catalyzed by Pd(0)
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The transformation of acyclic allylic benzamides 4 and homoallylic benzamides 12 to vinyl oxazolines 3 is achieved in the presence of base by the catalysis and Pd(0) in high yield and with high diastereoselectivity. Especially, in the case of homoallylic benzamides 12, trans-oxazolines 3 are formed exclusively or predominantly over cis-oxazolines 8, irrespective of the composition of their stereoisomers. The reaction is believed to proceed via the same π-allylpalladium complex that arises from either primary or secondary allylic acetates. We applied this method to the syntheses of β- amino-α-hydroxy acids 1 and γ-amino-β-hydroxy acids 2, conveniently protected as oxazoline.
- Lee, Kee-Young,Kim, Yong-Hyun,Park, Min-Sung,Oh, Chang-Young,Ham, Won-Hun
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p. 9450 - 9458
(2007/10/03)
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