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Seiichiro Ogawa

Other affiliations: Meisei University
Bio: Seiichiro Ogawa is an academic researcher from Keio University. The author has contributed to research in topics: Total synthesis & Hydroxymethyl. The author has an hindex of 31, co-authored 370 publications receiving 4730 citations. Previous affiliations of Seiichiro Ogawa include Meisei University.


Papers
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Journal ArticleDOI
TL;DR: A galactose derivative synthesized for chemical chaperone therapy of a human neurogenetic disease, β-galactosidosis, resulted in significant enhancement of the enzyme activity in the brain and other tissues and a marked decrease of intracellular substrate storage.
Abstract: We synthesized a galactose derivative, N-octyl-4-epi-β-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, β-galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal β-galactosidase in vitro. Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked decrease of intracellular substrate storage. Short-term oral administration of NOEV to a model mouse of juvenile GM1-gangliosidosis, expressing a mutant enzyme protein R201C, resulted in significant enhancement of the enzyme activity in the brain and other tissues. Immunohistochemical stain revealed a decrease in the amount of GM1 and GA1 in neuronal cells in the fronto-temporal cerebral cortex and brainstem. However, mass biochemical analysis did not show the substrate reduction observed histochemically in these limited areas in the brain probably because of the brief duration of this investigation. Chemical chaperone therapy may be useful for certain patients with β-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement.

253 citations

Book ChapterDOI
TL;DR: This chapter focuses on the chemistry of carbahexopyranoses and their derivatives, which are carbocyclic analogs of true disaccharides in which one or both of the hexose or pentose residues is(are) replaced with a carbasugar.
Abstract: Publisher Summary This chapter focuses on the chemistry of carbahexopyranoses and their derivatives. The first three carbasugars were synthesized by McCasland and coworkers. Two other carbasugars were prepared from myo -inositol and the remaining eleven carbasugars have been synthesized from the Diels–Alder adduct of furan and acrylic acid. Fifteen enantiomers have been synthesized among the thirty-two carbasugars theoretically predicted. D -Fructose is the sweetest sugar known in naturally occurring carbohydrates and its intense sweetness is produced only by β- D -fructopyranose. Carbaglycosylamines [2,3,4-trihydroxy-5-(hydroxymethyl)-1-cyclohexylamine] and related compounds are well known to exist as the components of antibiotic validamycin complex and carbaoligosaccharidic alpha amylase inhibitor. Carbadisaccharides are carbocyclic analogs of true disaccharides in which one or both of the hexose or pentose residues is(are) replaced with a carbasugar. Besides sweetness, a carbasugar may have biological activity owing to its structurally close resemblance to a true sugar. The chemistry of carba-sugars is a newly opened area ofchemistry and the biological effects of these compounds have not been well studied, except for (1) the equisweetness of D-carba-glucose, D-carba-galactose, and D-carba- fructose with the respective true sugars, (2) the antibiotic activity of α-D- carba-galactose, and (3) the inhibition of a D-glucose-stimulated insulin release by D-carba-glucose.

143 citations

Journal ArticleDOI
TL;DR: It is suggested that NOV works as a chemical chaperone to accelerate transport and maturation of F213I mutant β-Glu and may suggest a therapeutic value of this compound for GD.

128 citations

Journal ArticleDOI
TL;DR: The first total synthesis of the antibiotic (−)-hygromycin A (1) has been achieved by a coupling reaction of the sugar moiety and the cyclitol moiety.
Abstract: The first total synthesis of the antibiotic (−)-hygromycin A (1) has been achieved by a coupling reaction of the sugar moiety (2) and the cyclitol moiety (3). Both components were synthesized in homochiral forms starting from D-glucose. This synthesis fully confirmed the unique structure of 1, which is much different from other usual aminocyclitol antibiotics

78 citations

Journal ArticleDOI
TL;DR: A preliminary biological assay revealed that the stereochemistry at the 2-position of lycoricidine plays an important role in its cytotoxic activity.
Abstract: Stereoselective total synthesis of antimitotic alkaloid (+)-lycoricidine (1) and its 2-epimer (30) was accomplished starting from D-glucose. The key steps in this synthesis are (i) a catalytic version of the Ferrier rearrangement for the preparation of the optically active substituted cyclohexenone (the C-ring of lycoricidine) and (ii) a Pd-catalyzed intramolecular Heck-type reaction for construction of the phenanthridone skeleton. A preliminary biological assay revealed that the stereochemistry at the 2-position of lycoricidine plays an important role in its cytotoxic activity

75 citations


Cited by
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Journal ArticleDOI
TL;DR: In this paper, a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach called click chemistry is defined, enabled, and constrained by a handful of nearly perfect "springloaded" reactions.
Abstract: Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

9,069 citations

Journal ArticleDOI
TL;DR: In this paper, the authors show how in der Natur am haufigsten vorkommenden Verbindungen, so fallt auf, dass the Bildung von Kohlenstoff-Heteroatom-Bindungen gegenuber der von KHO-Kohlenstoffs-KHO-Bindingsen deutlich bevorzugt is, and das Medium naturlicher Reaktionen zumeist Wasser ist.
Abstract: Betrachtet man die in der Natur am haufigsten vorkommenden Verbindungen, so fallt auf, dass die Bildung von Kohlenstoff-Heteroatom-Bindungen gegenuber der von Kohlenstoff-Kohlenstoff-Bindungen deutlich bevorzugt ist Da zum einen Kohlendioxid die Basisverbindung der Natur ist und andererseits das Medium naturlicher Reaktionen zumeist Wasser ist, uberrascht dies sicherlich nicht Nucleinsauren, Proteine und Polysaccharide sind polymere Kondensationsprodukte kleiner Untereinheiten, die durch Kohlenstoff-Heteroatom-Bindungen verknupft sind Sogar die etwa 35 Baueinheiten, aus denen diese essentiellen Verbindungen bestehen, enthalten nicht mehr als sechs aufeinander folgende C-C-Bindungen, sieht man einmal von den drei aromatischen Aminosauren ab Mit der Natur als Vorbild richteten wir unser Interesse auf die Entwicklung leistungsfahiger, gut funktionierender und selektiver Reaktionen fur die effiziente Synthese neuartiger nutzlicher Verbindungen sowie kombinatorischer Bibliotheken mittels Heteroatomverknupfungen (C-X-C) Diese Synthesestrategie nennen wir „Click-Chemie“ Click-Chemie ist durch eine Auswahl einiger weniger nahezu idealer Reaktionen charakterisiert, mit all ihren Grenzen und Moglichkeiten In diesem Beitrag werden zum einen die strengen Kriterien, die Reaktionen erfullen mussen, um die Bezeichnung „Click-Chemie“ zu verdienen, definiert, zum anderen werden Beispiele fur molekulare Strukturen gegeben, die mit dieser spartanischen, aber dennoch leistungsfahigen Synthesestrategie leicht hergestellt werden konnen

1,380 citations

Journal ArticleDOI
TL;DR: The Shikimate Pathway as mentioned in this paper is a metabolic tree with many branches, which is a tree-structured approach for the analysis of the human metabolic pathway. Critical Reviews in Biochemistry and Molecular Biology: Vol. 25, No. 5, pp 307-384.
Abstract: (1990). The Shikimate Pathway — A Metabolic Tree with Many Branche. Critical Reviews in Biochemistry and Molecular Biology: Vol. 25, No. 5, pp. 307-384.

682 citations