Tetsuta Oshitari

Synthesis of 2-O-(3-O-carbamoyl-α-D-mannopyranosyl)-L-gulopyranose: Sugar moiety of antitumor antibiotic bleomycin

A new route to the disaccharide moiety (2-O-(3-O-carbamoyl-α-d-mannopyranosyl)-l-gulopyranose) of the antitumor agent bleomycin was developed. Both the l-gulose synthon 21 and the 3-O-carbamoyl-d-mannose segment 30 were prepared from d-mannose in a regioselective manner by applying stannylene acetal methodology. Glycosylation of 21 with 30 proceeded smoothly, and further conversion to disaccharide derivatives (33 and 34) was successfully accomplished.

New method for the preparation of L-gulose from D-mannose : synthetic study on the sugar moiety of bleomycin

Abstract l -gulose, a key building block of the carbohydrate moiety of antitumor antibiotic bleomycins, is prepared from d -mannose by the inversion at C-5.

Preparation of 2-O-(3-O-carbamoyl-α-d-mannopyranosyl)-l-gulopyranose: Synthetic study on the sugar moiety of antitumor antibiotic bleomycin

Abstract A new practical route to the disaccharide moiety of bleomycin was developed. Both of key building blocks 9 and 16 were prepared from d -mannose in a regioselective manner by applying stannylene acetal methodology. Glycosylation of the allyl alcohol 9 with the trichloroacetimidate 16 proceeded smoothly, and the further incorporation to the disaccharide moiety was successfully accomplished.

A synthetic model approach to the sugar moiety of bleomycin

In order to investigate the role of the sugar moiety of antitumor antibiotic bleomycin, glycosylation of erythro-β-hydroxy-L-histidine derivative is examined and several glycosylated model compounds are prepared by the chloroacetimidate method. These models show excellent dioxygen activating capability

[Development of a therapeutic agent for Menkes disease: solubilization of a copper-disulfiram complex].

Menkes disease (MD) is a neurodegenerative disorder characterized by copper deficiency. It is caused by defective intestinal absorption of copper resulting from a deficiency of a copper-transporting ATPase, ATP7A. We investigated the effects of combination therapy with copper and disulfiram, a known lipophilic chelator. We synthesized a copper-disulfiram complex (Cu-DSF) and determined its crystal structure by X-ray crystallographic analysis. Unfortunately, Cu-DSF was not orally bioavailable due to its lipophilicity. We therefore planned to use cyclodextrin as a solubilizing agent to increase the water solubility of Cu-DSF. After comparisons of the effects of cyclodextrins (α, β, γ), it was found that addition of β-cyclodextrin (β-CyD) increased the solubility of Cu-DSF. Moreover, the modified β-CyD, hydroxypropyl-β-cyclodextrin, was yet more effective as a solubilizing agent. For the development of a convenient method to determine the concentration of Cu-DSF included by β-cyclodextrins, a standard curve based on UV-visible(VIS) absorption was derived.