Home About us Contact
|
Home About us Contact | ||
|
|
||
Proline Derivatives (proline + derivative)
Selected AbstractsStereoselective Synthesis of ,-Proline Derivatives from Allylamines via Domino Hydroformylation/Wittig Olefination and Aza-Michael AdditionADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6 2010Andreas Farwick Abstract Under appropriate reaction conditions, a domino hydroformylation/Wittig olefination can be accomplished with derivatives of allylamines and stabilized Wittig ylides. A further highly diastereoselective aza-Michael reaction yields ,-proline derivatives. These are, for example, useful as building blocks for alkaloid syntheses. [source] New Simple Hydrophobic Proline Derivatives as Highly Active and Stereoselective Catalysts for the Direct Asymmetric Aldol Reaction in Aqueous MediumADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 2008Francesco Giacalone Abstract New 4-substituted acyloxyproline derivatives with different hydrophobic properties of the acyl group were easily synthesized and used as catalysts in the direct asymmetric aldol reaction between cyclic ketones (cyclohexanone and cyclopentanone) and several substituted benzaldehydes. Reactions were carried out using water, this being the best reaction medium examined. Screening of these catalysts showed that compounds bearing the most hydrophobic acyl chains [4-phenylbutanoate and 4-(pyren-1-yl)butanoate] provided better results. The latter catalysts were successfully used in only 2 mol% at room temperature without additives to give aldol products in excellent stereoselectivities. These results demonstrate that derivatization of the proline moiety with the proper simple hydrophobic substituent in the 4-position can furnish highly active and stereoselective catalysts without the need of additional chiral backbones in the molecule. Finally, an explanation of the observed stereoselectivities in the presence of water is provided. [source] ChemInform Abstract: Synthesis of Highly Functionalized Proline Derivatives via a One-Pot Michael/SN,-Addition/Cyclization Approach.CHEMINFORM, Issue 50 2009Uli Kazmaier Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Novel Approach to 5-Substituted Proline Derivatives Using a Silver-Catalyzed Cyclization as the Key Step.CHEMINFORM, Issue 31 2005Bart C. J. van Esseveldt Abstract For Abstract see ChemInform Abstract in Full Text. [source] Increased rigidity of the chiral centre of tocainide favours stereoselectivity and use-dependent block of skeletal muscle Na+ channels enhancing the antimyotonic activity in vivoBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2001Sophie Talon Searching for the structural requirements improving the potency and the stereoselectivity of Na+ channel blockers as antimyotonic agents, new derivatives of tocainide, in which the chiral carbon atom is constrained in a rigid ,-proline or pyrrolo-imidazolic cycle, were synthesized as pure enantiomers. Their ability to block Na+ currents, elicited from ,100 to ,20 mV at 0.3 Hz (tonic block) and 2 , 10 Hz (use-dependent block) frequencies, was investigated in vitro on single fibres of frog semitendinosus muscle using the vaseline-gap voltage-clamp method. The ,-proline derivative, To5, was 5 and 21 fold more potent than tocainide in producing tonic and 10 Hz-use-dependent block, respectively. Compared to To5, the presence of one methyl group on the aminic (To6) or amidic (To7) nitrogen atom decreased use-dependence by 2- and 6-times, respectively. When methylene moieties were present on both nitrogen atoms (To8), both tonic and use-dependent block were reduced. Contrarily to tocainide, all proline derivatives were stereoselective in relation to an increased rigidity. A further increase in the molecular rigidity as in pyrrolo-imidazolic derivatives markedly decreased the drug potency with respect to tocainide. Antimyotonic activity, evaluated as the shortening of the time of righting reflexes of myotonic adr/adr mice upon acute drug in vivo administration was 3 fold more effective for R-To5 than for R-Tocainide. Thus, constraining the chiral centre of tocainide in ,-proline cycle leads to more potent and stereoselective use-dependent Na+ channel blockers with improved therapeutic potential. British Journal of Pharmacology (2001) 134, 1523,1531; doi:10.1038/sj.bjp.0704366 [source] Synthesis and Glycosidase Inhibitory Activities of Pyrrolidines and Piperidines with N -(Polyhydroxyalkyl) Side ChainsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2007Sabrina Boutefnouchet Abstract Amidification of L -proline (3) with (+)-(R,R)- 6 and (,)-(S,S)-tartaric anhydride diacetate (7) gave N -substituted L -proline derivatives 8a,b, respectively. Acids 8a,b were transformed into diesters 9a,b with MeOH/HCl. Similar reactions with methyl (2S,4R)- 4 and (2R,4S)-4-acetoxypipecolate (5) led to bicyclic lactams 14a,b and 15a. Compounds 8a,b were converted into N -(trihydroxybutyl)pyrrolidine derivatives 8c,d, 10a,b and 11a,b. Methyl (2S,4R)- 20a and (2R,4S)-4-acetoxy- N -[(2S,3S)-1,2,3-trihydroxybutyl]pipecolate (20b) were obtained by displacement of (,)-(2S,2S)-2- O -benzyl-3,4- O -isopropylidene-1-deoxy-1-iodothreitol (19) by 4 and 5. Compounds 20a,b were converted into (2S,4R,2,S,2,S)- 21a and(2R,4S,2,S,3,S)-4-hydroxy-2-hydromethyl- N -(2-benzyloxy-3,4-isopropylidenedioxy)piperidine (21b) and finally into unprotected pentols 22a,b. Nonprotected (2S,2,S,3,S)- 11a and (2S,2,R,3,R)- N -(1,2,3-trihydroxybutyl)prolinol (11b), as well as 22a,b, did not inhibit any of the 13 glycosidases assayed. However, a triacetoxy derivative, (2S,3S)-2,3-diacetoxy-4-[(2R,4S)-4-acetoxy-2-(methoxycarbonyl)piperidin-1-yl]-4-oxobutanoic acid (13b) is an inhibitor (IC50 = 157 ,M) of ,- L -fucosidase from bovine kidney.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Stereoselective Synthesis of ,-Proline Derivatives from Allylamines via Domino Hydroformylation/Wittig Olefination and Aza-Michael AdditionADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6 2010Andreas Farwick Abstract Under appropriate reaction conditions, a domino hydroformylation/Wittig olefination can be accomplished with derivatives of allylamines and stabilized Wittig ylides. A further highly diastereoselective aza-Michael reaction yields ,-proline derivatives. These are, for example, useful as building blocks for alkaloid syntheses. [source] Highly Efficient Asymmetric Michael Reaction of Aldehydes to Nitroalkenes with Diphenylperhydroindolinol Silyl Ethers as OrganocatalystsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 14-15 2009Ren-Shi Luo Abstract New dihydroindole and perhydroindole derivatives were synthesized in good yields and evaluated as chiral catalysts in the asymmetric Michael reaction of aldehydes to nitroalkenes. (2S,3aS,7aS)-Diphenylperhydroindolinol silyl ether 10 facilitated the reaction of a wide range of aldehyde and nitroalkene substrates, providing Michael adducts in nearly optically pure form (99% ee), good yields and high diastereoselectivities (syn/anti up to 99:1). These results show for the first time that perhydroindole derivatives can also be highly efficient organocatalysts for the asymmetric Michael reaction, exhibiting comparable or even better enantioselectivities than proline derivatives. [source] Increased rigidity of the chiral centre of tocainide favours stereoselectivity and use-dependent block of skeletal muscle Na+ channels enhancing the antimyotonic activity in vivoBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2001Sophie Talon Searching for the structural requirements improving the potency and the stereoselectivity of Na+ channel blockers as antimyotonic agents, new derivatives of tocainide, in which the chiral carbon atom is constrained in a rigid ,-proline or pyrrolo-imidazolic cycle, were synthesized as pure enantiomers. Their ability to block Na+ currents, elicited from ,100 to ,20 mV at 0.3 Hz (tonic block) and 2 , 10 Hz (use-dependent block) frequencies, was investigated in vitro on single fibres of frog semitendinosus muscle using the vaseline-gap voltage-clamp method. The ,-proline derivative, To5, was 5 and 21 fold more potent than tocainide in producing tonic and 10 Hz-use-dependent block, respectively. Compared to To5, the presence of one methyl group on the aminic (To6) or amidic (To7) nitrogen atom decreased use-dependence by 2- and 6-times, respectively. When methylene moieties were present on both nitrogen atoms (To8), both tonic and use-dependent block were reduced. Contrarily to tocainide, all proline derivatives were stereoselective in relation to an increased rigidity. A further increase in the molecular rigidity as in pyrrolo-imidazolic derivatives markedly decreased the drug potency with respect to tocainide. Antimyotonic activity, evaluated as the shortening of the time of righting reflexes of myotonic adr/adr mice upon acute drug in vivo administration was 3 fold more effective for R-To5 than for R-Tocainide. Thus, constraining the chiral centre of tocainide in ,-proline cycle leads to more potent and stereoselective use-dependent Na+ channel blockers with improved therapeutic potential. British Journal of Pharmacology (2001) 134, 1523,1531; doi:10.1038/sj.bjp.0704366 [source] | ||||||||||