Kenji Ogino

Apoptotic activities of C2-ceramide and C2-dihydroceramide homologues against HL-60 cells

The apoptotic activities of non-natural ceramide homologues, C2-homo-ceramide, C2-homo-dihydroceramide, C2-bishomo-ceramide and C2-bishomo-dihydroceramide, were examined using human leukemia HL-60 cells. The apoptotic activity was in order of C2-ceramide>C2-homo-ceramide approximately C2-bishomo-ceramide and the activities of the L-erythro- and D-erythro-ceramide homologues were similar. The morphological features of the cells, DNA fragmentations, proteolytic processing of pro-caspase-3 and the cleavage of PARP as the result of treatments with these homologues indicated that cell death was induced by apoptosis.

Synthesis of novel and non-natural ceramide analogues derived from L-glutamic acid

Abstract Novel and non-natural ceramide analogues, having a different methylene spacer between the primary hydroxymethyl group and aminomethane of sphingosine backbone, have been prepared from l -glutamic acid. The key step in the preparation is the diastereoselective reduction of an enone adjacent to a Boc protected amino group by reducing agents.

Synthesis of non-natural C2-homo-ceramide and its apoptotic activity against HL-60 cells.

Non-natural ceramide analogues, C2-homo-ceramide and C2-homo-dihydroceramide, were prepared from L-aspartic acid via L-homo-serine. The apoptotic activities of the synthesized ceramide analogues were examined in HL-60 human leukemia cells. C2-homo- and C2-bishomo-ceramide indicate low but considerable apoptotic activities in comparison with C2-ceramide.

Ester substrate PNIQ as a novel fluorescent probe for the study of acylation and deacylation steps in ester hydrolysis catalyzed by lipophilic imidazole·Zn2+ complexes in micelles

Abstract p-Nitrophenyl isoquinoline-3-carboxylate ( PNIQ ) has been found to be a versatile ester substrate for the study of catalytic activities of lipophilic imidazole·Zn 2+ complexes in cationic micelles, i.e. PNIQ allows to monitor the rates of both acylation of a catalyst-complex by a uv method and of deacylation of the acylated intermediate to regenerate the catalyst-complex by a fluorescent method.

Rearrangement of tertiary amine N-oxides—XXVII : Mechanism of the reaction of isoquinoline N-oxide with substituted benzenesulfonyl chlorides☆

Abstract Kinetic experiments have been carried out on the reactions of isoquinoline N-oxide with p-toluenesulfonyl and other substituted benzenesulfonyl chlorides, varying solvent and salt compositions. The rate was correlated by the second-order equation, i.e., v = [N → O] × [ArSO2Cl], and was found to be accelerated in polar media. The addition of chloride ion was found to increase the rate considerably, while the rates of the over-all reaction became greater with arenesulfonyl chlorides bearing stronger electron-withdrawing substituents (ϱ = +2·0). By the use of 1-deuterated isoquinoline N-oxide a small kinetic isotope effect (kH/kD = 1·2) was observed for this reaction. Based on these kinetic observations the rate-determining step of this reaction is considered to be the cleavage of NO bond. Meanwhile, from the 18O-tracer experiments in several solvents using uniformly 18O-labelled p-toluenesulfonyl or p-bromobenzenesulfonyl chloride the migration of arenesulfonate was found to proceed mainly via oxygen-bridged ion pair pathway.

Mechanisms of the reactions of substituted iso-quinoline and quinoline N-oxides with arenesulfonyl chlorides

Abstract The rearrangements of substituted iso-quinoline and quinoline N-oxides with arenesulfonyl chlorides have been carried out to clarify the mode of migration of the arenesulfonoxy group by means of both 18O tracer and kinetic experiments. In the rearrangements of N-arenesulfonoxy-iso-carbostyril and carbostyril, the main migration route of the arenesulfonoxy group is via the solvent separated ion pair path with a minor portionpassing throug step appears to be NO bond cleavage. For 1-amino-iso-quinoline N-oxide the migration of tosyloxy group to 1-amino-4-tosyloxyiso-quinoline through the oxygen-bridged ion pair pathway is so fast that the presence of the anhydro base cannot be detected. Reaction of 2-aminoquinoline N-oxide to afford 2-amino-6-tosyloxyquinoline which involves migration to a distant position proceeds rapidly, apparently through the solvent separated ion pair path.

Rate enhancing multi-site interactions in ester hydrolysis catalyzed by Cu2+ complexes of surfactant imidazole ligands in non-ionic micelles

Abstract The Cu 2+ complexes of surfactant imidazole ligands, having a hydroxyl and a cationic or an anionic polar head groups, were found to be highly active catalysts for the hydrolysis of p -carboxyphenyl picolinate, when the reaction is conducted under micellar conditions. The multisite interactions in the formation of a reactive ternary complex appears to be important for the rate enhancement in non-ionic PGLE micelles.

Réactivé d'iminophosphoranes polyfonctionnalisés

Abstract The reactivity of some functionaltzed azides has been studied under the conditions of the Staudinger and aza-Wittig reactions. With the azides having a trifluoroacetamido group in the ortho-position of the aromatic ring, intramolecular reactions have been observed which allow new synthetic approaches to indoline and imidazoindole compounds.

Reaction of lepidine, quinaldine and 1-methylisoquinoline N-oxides with acetic anhydride

Abstract The mechanism of the reactions of lepidine, quinaldine and 1-methylisoquinoline N-oxides with acetic anhydride has been studied by means of both kinetic and 18 O tracer experiments. In all cases, the over-all rate of the reaction is markedly affected both by the change of solvent and by the addition of salts. In the case of lepidine N-oxide, a large kinetic isotope effect, k H /k D = 7·7 in acetonitrile, suggests that the proton-removal is the rate-determining step. This is also the case for 6-methylquinaldine N-oxide which gives the kinetic isotope effect, k H / k D = 7·4 (at 30·). In the case of quinaldine N-oxide, however, the kinetic isotope effect is small, k H / k D (at 30°), while quinaldine N-oxide originally trideuterated loses deuterium during the reaction, depicting that the proton-removal is a reversible step and the succeeding NO bond cleavage is the rate-determining step. In the case of 1-methylisoquinoline N-oxide, in which k H / k D is 3·5 in dioxan at 30· both proton-removal and NO bond cleavage are equally important in the energy profile of the reaction.