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H Ishitani

Publications and source records attributed to H Ishitani.

5 recordsLinked to original sources
PubMed2001

A novel inhibitor of ceramide trafficking from the endoplasmic reticulum to the site of sphingomyelin synthesis.

Ceramide produced at the endoplasmic reticulum (ER) is transported to the lumen of the Golgi apparatus for conversion to sphingomyelin (SM). N-(3-Hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12) is a novel analog of ceramide. Metabolic labeling experiments showed that HPA-12 inhibits conversion of ceramide to SM, but not to glucosylceramide, in Chinese hamster ovary cells. Cultivation of cells with HPA-12 significantly reduced the content of SM. HPA-12 did not inhibit the activity of SM synthase. The inhibition of SM formation by HPA-12 was abrogated when the Golgi apparatus was made to merge with the ER by brefeldin A. Moreover, HPA-12 inhibited redistribution of a fluorescent analog of ceramide, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-d-erythro-sphingosine (C(5)-DMB-Cer), from intracellular membranes to the Golgi region. Among four stereoisomers of the drug, (1R,3S)-HPA-12, [corrected] which resembles natural ceramide stereochemically, was found to be the most active, although (1R,3S)-HPA-12 [corrected] did not affect ER-to-Golgi trafficking of protein. Interestingly, (1R,3S)-HPA-12 [corrected] inhibited conversion of ceramide to SM little in mutant cells defective in an ATP- and cytosol-dependent pathway of ceramide transport. These results indicated that (1R,3S)-HPA-12 [corrected] inhibits ceramide trafficking from the ER to the site of SM synthesis, possibly due to an antagonistic interaction with a ceramide-recognizing factor(s) involved in the ATP- and cytosol-dependent pathway.

Amides↗
PubMed2000

Chiral catalyst optimization using both solid-phase and liquid-phase methods in asymmetric aza Diels-Alder reactions

[formula: see text] In the presence of 1-5 mol % of a chiral zirconium catalyst, aza Diels-Alder reactions of aldimines with Danishefsky's dienes proceeded smoothly to afford the corresponding piperidine derivatives in high yields with high enantioselectivities. For the catalyst optimization, solid-phase and liquid-phase methods were successfully used. In the solid-phase approach, polymer-supported (R)-1,1'-binaphthols (BINOLs) have been synthesized and rapid optimization using the solid-phase reactions has been achieved. On the other hand, novel chiral zirconium cyanides were developed as excellent catalysts using the liquid-phase approach.

Journal Article↗
PubMed2000

Novel binuclear chiral zirconium catalysts used in enantioselective strecker reactions.

A novel binuclear chiral zirconium catalyst was successfully used in enantioselective Strecker reactions. The catalyst was readily prepared from zirconium t-butoxide (Zr(OtBu)4), (R)-6,6'-dibromo-1, 1'-bi-2-naphthol ((R)-6-Br-BINOL), and (R)-3,3'-dibromo-1, 1'-bi-2-naphthol ((R)-3-Br-BINOL) to form unique binuclear structure. It was revealed that a combination of (R)-6-Br-BINOL and (R)-3-Br-BINOL was essential in these asymmetric reactions and that much lower selectivities were obtained by using other combinations. Two-component (an imine and hydrogen cyanide (HCN)) and three-component (an aldehyde, an amine, and HCN) Strecker reactions proceeded smoothly in the presence of a catalytic amount of the chiral zirconium catalyst to afford the corresponding alpha-amino nitrile derivatives in high yields with high enantioselectivities.

Journal Article↗
PubMed1998

A convenient method for library construction: parallel synthesis of beta-amino ester and quinoline derivatives in liquid phase using Ln(OTf)3-catalyzed three-component reactions

A convenient method for library construction in liquid phase, which is based on lanthanide triflate (Ln(OTf)3)-catalyzed three-component reactions, has been developed. Equimolar amounts of each component, an aldehyde, an amine, and a silyl enol ether or an alkene, react smoothly in the presence of Ln(OTf)3, and the work-up and purification processes are performed by simply passing through a short column. The key is to use Ln(OTf)3 as a Lewis acid catalyst, which is not decomposed during the work-up and purification steps, and is easily separated from products by the simple procedure. According to this method, various high-quality beta-amino ester and quinoline derivatives have been prepared in parallel in large quantities. Copyright 1998 John Wiley & Sons, Inc.

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