Enantioseparation of four cis and trans diastereomers of 2',3'-didehydro-2',3'-dideoxythymidine analogs, by high-performance liquid chromatography and capillary electrophoresis.

Compounds 1-4 are the four stereoisomers of a synthetic new potential antiviral agent (d4T analog) containing two chiral centers and a base (uracil). Both high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) techniques were used to separate and quantify enantiomers with high resolution. The determination of enantiomeric purity of the compounds was developed using both amylose chiral stationary phase by HPLC and anionic cyclodextrins (highly S-CD) as chiral selectors in CE. The HPLC method was found to be superior in sensitivity to the CE method.

Spirohydantoins from D-ribose as new potent enzymatic inhibitors.

Anomeric spirohydantoin derivatives from monosaccharides are known for various biological properties. We describe herein the synthesis of the 3-spirohydantoin derivatives of D-allose and D-ribose. The key step is the stereoselective glyco-alpha-aminonitrile formation from ulose derivatives of D-glucose and D-xylose using titanium tetra-isopropoxide as a mild and efficient catalyst. Target compounds were synthesized from these intermediates. The glucidic moiety was partially or totally deprotected under acidic conditions. These new heterocyclic monosaccharidic derivatives are potent glycogen phosphorylase inhibitors.

Synthesis and antifungal activity of novel bisdithiocarbamate derivatives of carbohydrates against Fusarium oxysporum f. sp. lini.

Novel carbamic esters possessing a carbohydrate moiety derived from glycerol or D-glucose with two N,N-diethyldithiocarbamoyl groups and a series of bisdithiocarbamic esters having a ketone or an alkyl ester have been synthesized. The in vitro activity of these new compounds was evaluated against Fusarium oxysporum f. sp. lini. Some of the compounds [bis[1,3-S-(N,N-diethyldithiocarbamoyl)]-1, 3-dideoxyglycerol) and diethyl N,N'-(1,3-dideoxyglycer-1, 3-diyl)bis(dithiocarbamate)] were more active for inhibiting vegetative mycelium growth than, respectively, the commercial N, N-diethyldithiocarbamic acid sodium salt and Maneb. The structure activity of these new compounds is discussed.

3-Acetyl deoxynivalenol production in a strain ofFusarium culmorum insensitive to the fungicide difenoconazole.

The production of the mycotoxin, 3-acetyl deoxynivalenol (3-ADON), was investigated in a strain ofFusarium culmorum insensitive to the systemic fungicide, difenoconazole. On exposure to graded concentrations of the fungicide, the insensitive strain continued to synthesise 3-ADON when difenoconazole levels of 100 and 200µg/ ml media were used. In contrast, a control (sensitive) strain ceased production of 3-ADON at difenoconazole levels of 100 µg/ml. Differences between the two strains were also observed for 3-ADON production with time. Following incubation with fungicide at 0.1 µg/ ml, 3-ADON production occurred more rapidly in CS than in IS cultures. This is the first report of increased persistence and alteration of the pattern of production of a mycotoxin following the development of fungicide insensitivity in a fungal phytopathogen.

Novel monoacetoneglucose derivatives with calcium antagonist activity.

Ethers and thioethers of monosaccharides have been synthesised which show potent toxicity to mouse (LD50 > or = 4 g.kg-1 O.W. and 0.2 to 1.5 g.kg-1 I.P.W.). A study of calcium antagonist activity for the full series of compounds indicated that the activity was similar for both O- and S- ethers and maximum activities were observed for monoacetoneglucose ethers possessing carbon chain close to 8 carbons.

[Effect of the nature of the heteroatom of a monosaccharide derivative on its inhibitory action in relation to P-type calcium channels expressed in the Xenopus oocyte]. / Influence de la nature de l'hétéroatome d'un dérivé monosaccharidique sur son action inhibitrice vis à vis de canaux calciques apparentés au type P exprimés dans l'ovocyte de Xenopus.

Our results demonstrate that saccharidic derivatives obtained by adding a C8 alkyl group through various heteroatomes (O, N or S) to a monoacetonide residue possess an inhibitory effect towards putative P-type calcium channels expressed in Xenopus oocytes. These derivatives partially and reversibly inhibit the activity these channels without changing their electrophysiological properties. Nevertheless, the derivative containing the heteroatome N also affects the fast and tetrodotoxin-sensitive sodium channel activity. Thus, only ether and thioether compounds (heteroatome O or S) can be selected for their inhibitory effect on P-type apparented calcium channels.