Voici les éléments 1 - 10 sur 183
- PublicationMétadonnées seulementProbing the Active Site of Pseudomonas aeruginosa Porphobilinogen Synthase Using Newly Developed Inhibitors(2006)
;Frere, Frederic ;Nentwich, Merle ;Gacond, Sabine ;Heinz, Dirk W. ;Frankenberg-Dinkel, NicolePorphobilinogen synthase catalyzes the first committed step of the tetrapyrrole biosynthesis pathway. In an aldol-like condensation, two mols. of 5-aminolevulinic acid (ALA) form the first pyrrole, porphobilinogen. Newly synthesized analogs of a reaction intermediate of porphobilinogen synthase have been employed in studying the active site and the catalytic mechanism of this early enzyme of tetrapyrrole biosynthesis. This study combines structural and kinetic evaluation of the inhibition potency of these inhibitors. In addn., one of the detd. protein structures provides for the first time structural evidence of a magnesium ion in the active site. From these results, we can corroborate an earlier postulated enzymic mechanism that starts with formation of a C-C bond, linking C3 of the A-side ALA to C4 of the P-side ALA through an aldole addn. The obtained data are discussed with respect to the current literature. [on SciFinder(R)]
- PublicationMétadonnées seulementApplication of the novel tandem process Diels-Alder reaction/Ireland-Claisen rearrangement to the synthesis of rac-juvabione and rac-epijuvabione(2000-1-12)
;Soldermann, Nicolas ;Velker, Joerg ;Vallat, Olivier ;The novel tandem process Diels-Alder reaction/Ireland-Claisen rearrangement shows a high diastereoselectivity for the Ireland-Claisen rearrangement starting from the endo-product of the Diels-Alder reaction. Based on this mechanistic knowledge, the novel tandem process could be applied to the synthesis of rac-juvabione.
- PublicationMétadonnées seulementCatalytic Epoxidation of Alkenes by the Manganese Complex of a Reduced Porphyrinogen Macrocycle(2012)
;Bruyneel, Frederic ;Letondor, Christophe ;Bastuerk, Bjorn ;Gualandi, Andrea ; ;The present paper details the first application of a fully reduced meso-octamethylporphyrinogen macrocycle as an effective ligand for simple operative manganese-catalyzed alkene epoxidn. The efficiency of the novel catalyst was detd. in the presence of various oxidants, apical ligands and acidic/basic additives. Higher reactivity was found in favor of electron-rich alkenes, whereas an electron-deficient conjugated alkene appeared to be a poor substrate in the screening. Sulfur additives were active as apical ligands, whereas nitrogen-contg. additives influenced the reactivity only moderately. Cis-Stilbene and 3?-acetoxy-5-cholestene were epoxidized in a stereoselective manner. The x-ray structures of the new manganese complexes were detd. and showed a rigid planar coordination geometry of the satd. macrocyclic ligand to the metal center. [on SciFinder(R)]
- PublicationMétadonnées seulementAn Efficient Photoinduced Deprotection of Aromatic Acetals and Ketals(2011)
;A novel type of photodeprotection reaction of simple arom. acetals and ketals is described. The deprotection is highly efficient under optimized conditions. The arom. ring confers the photoreactivity to the compds. The efficiency of the process depends on the structure of the acetal moiety. The common minor side reaction, the photooxidn., becomes the major reaction pathway in the case of cyclic acetals. The use of photon as only reagent makes this procedure esp. attractive for acetal deprotection. [on SciFinder(R)]
- PublicationMétadonnées seulementStructure of yeast 5-aminolevulinic acid dehydratase complexed with the inhibitor 5-hydroxylevulinic acid(2005)
;Erskine, P. T. ;Coates, L. ;Newbold, R. ;Brindley, A. A. ;Stauffer, Frederic ;Beaven, G. D. E. ;Gill, R. ;Coker, A. ;Wood, S. P. ;Warren, M. J. ;Shoolingin-Jordan, P. M. ;Cooper, J. B.The x-ray crystal structure of 5-aminolevulinate dehydratase (ALAD) of yeast complexed with the competitive inhibitor, 5-hydroxylevulinic acid, was detd. at a resoln. of 1.9 Å. The structure showed that the inhibitor was bound by a Schiff-base link to one of the invariant active site Lys residues (Lys-263). The inhibitor appeared to bind in 2 well-defined conformations and the interactions made by it suggested that it is a very close analog of the substrate, 5-aminolevulinic acid (ALA). [on SciFinder(R)]
- PublicationMétadonnées seulementSyntheses of rhazinilam. A comparative review of forty years of synthetic endeavors(2011)
;Kholod, Inga ;Vallat, Olivier ;A review. R-(-)-Rhazinilam is a relatively simple but unusual monopyrrolic product isolated from nature. It is probable that R-(-)-rhazinilam is an artifact of the isolation procedure. Seven total syntheses of rhazinilam were described in the literature. The comparison of the published syntheses clearly demonstrates the sensitivity of the pyrrole ring contained in the rhazinilam structure. Despite the spectacular progress in org. synthetic methods only a few synthetic strategies were applied to the total synthesis of rhazinilam. Astonishingly the no. of steps needed from com. starting materials has stayed similar over the almost 40 yr period since the first synthesis was reported in 1973. [on SciFinder(R)]
- PublicationMétadonnées seulementStructure of yeast 5-aminolaevulinic acid dehydratase complexed with the inhibitor 5-hydroxylaevulinic acid(2005)
;Erskine, P. T. ;Coates, L. ;Newbold, R. ;Brindley, A. A. ;Stauffer, Frederic ;Beaven, G. D. E. ;Gill, R. ;Coker, A. ;Wood, S. P. ;Warren, M. J. ;Shoolingin-Jordan, P. M. ;Cooper, J. B.The X-ray structure of the enzyme 5-aminolaevulinic acid dehydratase (ALAD) from yeast complexed with the competitive inhibitor 5-hydroxylaevulinic acid has been determined at a resolution of 1.9 A. The structure shows that the inhibitor is bound by a Schiff-base link to one of the invariant active-site lysine residues (Lys263). The inhibitor appears to bind in two well defined conformations and the interactions made by it suggest that it is a very close analogue of the substrate 5-aminolaevulinic acid (ALA).
- PublicationMétadonnées seulementEthylene glycol and amino acid derivatives of 5-aminolevulinic acid as new photosensitizing precursors of protoporphyrin IX in cells(2000)
;Berger, Yann ;Greppi, Alain ;Siri, Olivier ;Juillerat-Jeanneret, LucienneProtoporphyrin IX (PpIX) is used as a photosensitizing agent in photodynamic detection and therapy (PDT) of cancer and is synthesized intracellularly from aminolevulinic acid (ALA) precursors. To evaluate means to specifically target ALA derivatives to defined cells, we have synthesized and characterized ethylene glycol esters and amino acid pseudodipeptide derivatives of ALA as potential specific substrates for cellular esterases and aminopeptidases, respectively. The PpIX formation induced by these products was investigated using cultures of human and rat cell Lines of carcinoma and endothelial origins. The cytotoxicity of these compounds in the absence of light was also controlled. The results have shown that ethylenglycol esters can induce high levels of PpIX and are useful at concentrations below their cytotoxicity threshold. From the ALA-amino acid derivatives which were evaluated, the highest PpIX production was obtained using ALA derivatives of neutral amino acids, as compared to acidic or basic amino acids.
- PublicationMétadonnées seulementDiastereoselective synthesis of (1S,2S,3R,6S) 3-chloro-3-methyl-6-isopropenyl-1,2-cyclohexanediol via Prins reaction induced by zinc and trimethylsilyl chloride(1996)
;Marty, Maurus ;While attempting to synthesize a potential inhibitor of the biosynthetic step of formation of PEG, a novel catalytic system inducing the Prins reaction was discovered. Treatment of epoxy geranial with Zn and trimethylsilyl chloride gave (1S,2S,3R,6S) 3-Chloro-3-methyl-6-isopropenyl-1,2-cyclohexanediol in high diastereoselcctivity.
- PublicationAccès libreAn Unexpected Tandem Reaction between N-Butadienyl-N-alkylketeneN,0-Trimethylsilylacetals of Propionamide and Activated Dienophiles like N-Phenylmaleimide or Acryloyl Chloride(1993)
;Baak, Marcel ;Rubin, Yves ;Franz, Andreas ; ;Bigler, Laurant ;Nachbauer, JürgenStarting from the N-butadienyl-N-alkylpropionamides 1a-1c the corresponding N,0-trimethylsilylacetals could be obtained using the mixture ofLDA and trimethylsilyl chloride in THF. The unexpected reaction sequence Diels-Alder reaction/acylation between the N-butadienyl-N-alkylketene N,0-trimethylsilylacetal ofpropionamide (2a-2b) and N-phenylmaleimide produced tricyclic products rac-5a -rac-5b and bicyclic products rac-6a - rac-6b with high diastereoselectivity. The reaction of the N,0-trimethylsilylacetals 2a and 2c with acryloyl chloride in a similar sequence gave the bicyclic products rac-8a and mc-8c. The stepwise synthesis of bicyclic systems of this general structure could only be successfully executed in 26 yield treating the Diels-Alder product rac-10 with LDA.