Synthesis and cytotoxic profile of glycosyl-triazole linked to 1,2,4-oxadiazole moiety at C-5 through a straight-chain carbon and oxygen atoms.

The convergent synthesis of an unusual (but simple) class of compounds 5a-g has been achieved by the copper-catalyzed [3+2] cycloaddition reaction of 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide 4 with propynyl 3-[3-(aryl)-1,2,4-oxadiazol-5-yl] propionates 3a-g. The formerly known azide 4 has been prepared according to the literature procedure; however, the synthesis of esters 3a-g is being reported for the first time. The infrared as well as (1)H NMR spectra of all new products are in agreement with their proposed structures. By carrying out the nOe experiment of one of the final compounds 5a, we have been able to establish that only the 1,4-regioisomers have been formed in the cycloaddition reaction. All final products presented weak cytotoxic activity, but 5e and 5g had somewhat better behaviour showing 22-25% cell growth inhibition against two cell strains: NCI-H(292) (lung carcinoma) and HEp-2 (larynx carcinoma).

Synthesis of glycosyl-triazole linked 1,2,4-oxadiazoles.

The synthesis of four different types of oxadiazoles containing a terminal acetylenic group is described. Reaction of these oxadiazoles with various azidoglycosides via a copper-catalyzed [3+2] cycloaddition ('click chemistry') afforded the corresponding glycosyl-triazole linked 1,2,4-oxadiazoles in good yields.

Total synthesis and identification of two diastereoisomers of 1-methyl-2-[N-(p-tolylsulfonyl)-2-pyrrolidinyl]ethyl beta-L-fucopyranoside.

The reaction of a racemic mixture of (2R,2'S)- and (2S,2'R)-N-(p-tolylsulfonyl)-2-pyrrolidinyl-2-propanol, prepared from (S)-proline, with 2,3,4-tri-O-acetyl-alpha-L-fucopyranosyl trichloroacetimidate led to both diastereoisomers of the title compound after O-deacetylation.

Epoxidation and bis-hydroxylation of C-phenyl-delta(2,3)-glycopyranosides.

Epoxidation and cis-hydroxylation of C-phenyl-delta(2,3)-glycopyranosides have been carried out with a view to developing C-aryl glycoside synthesis. Epoxidation of (2,3- and (6-O-tert-butyldimethylsilyl-2,3-dideoxy-D-erythro-hex-2-enopyranosyl)benzenedideoxy-D-erythro-hex-2-enopyranosyl)benzene gave predominantly the allo-adducts whatever the configuration at the anomeric center. Epoxidation of (4,6-di-O-tert-butyl-dimethylsilyl-2,3-dideoxy-D-erythro-hex-2-enopyranosyl)benzene gave the manno- and allo-adducts in a 89:11 and 40:60 ratios for the alpha- and beta-anomers, respectively. Hydroxylation of alpha-C-phenyl-(2,3)-glycopyranosides using OsO4 afforded the manno-adduct only, whatever the substituents at positions 4 and 6, whereas hydroxylation of (2,3-dideoxy-beta-D-erythro-hex-2-enopyranosyl)benzene and (4,6-di-O-tert-butyldimethylsilyl-2,3-dideoxy- beta-D-erythro-hex-2-enopyranosyl)benzene gave the manno- and allo-adducts in 25:75 and 80:20 ratios, respectively.

Enantiopure fluorous bis(oxazolines): synthesis and applications in catalytic asymmetric reactions.

Various enantiopure fluorous bis(oxazolines) with fluorine content between 52.7 and 58.7% have been synthesized by a simple reaction sequence that involved the introduction of two fluorinated ponytails by alkylation of the corresponding nonfluorous bis(oxazolines). These new ligands have been used in palladium-catalyzed alkylation of rac-(E)-1,3-diphenylpropenyl acetate with carbon nucleophiles and in copper-catalyzed oxidation of cycloalkenes; these ligands exhibited enantioselectivities up to 98 and 77%, respectively, quite close to the values obtained using the analogous nonfluorous bis(oxazolines). These ligands could be easily recovered by liquid-liquid extraction or solid-liquid separation and reused with the same enantioselectivities.

Synthesis of new branched-chain amino sugars.

1,3-Dipolar cycloaddition of methylideneaniline N-oxide to sugar enones is described. The addition occurred exclusively from the side opposite to the aglycone affording the corresponding alkyl alpha-D-lyxo-hexopyranosid-(2,3:5',4')-phenylisoxazolidin-4-uloses. Hydrogenation of these compounds readily yielded the corresponding alkyl 3-deoxy-3-N-phenylaminomethyl-alpha-D-talopyranoside, that were readily transformed to the acetates. The structure and conformation of the bicyclic compounds were determined by 1H NMR studies and semi-empirical molecular orbital calculations employing the AM1 method.

Synthesis of alpha- and beta-C-Aryl Delta(2)-Glycopyranosides from p-tert-Butylphenyl Delta(2)-Glycopyranosides via Grignard Reagents.

Treatment of p-tert-butylphenyl 4,6-di-O-benzyl-2,3-dideoxy-alpha-D-erythro-hex-2-enopyranoside (1aalpha) or the 4,6-di-O-(tert-butyldimethylsilyl) analogue (1balpha) with various functionalized arylmagnesium bromides in the presence of a catalytic amount of PdCl(2)(dppf) at 25 degrees C in THF afforded the corresponding unsaturated C-arylglycosides 2-14 having the alpha-configuration in quite good yields. Benzyl-, allyl-, and vinylmagnesium bromides gave also the corresponding unsaturated alpha-C-glycosides 15-18, although in lower yields. When the same reaction was performed in the presence of NiCl(2)(dppe) as the catalyst at -40 degrees C, only the formation of the corresponding unsaturated C-arylglycosides having the beta-configuration was observed. As expected, reaction of phenylmagnesium bromide with p-tert-butylphenyl 4,6-di-O-benzyl-2,3-dideoxy-beta-D-erythro-hex-2-enopyranoside (1abeta) in the presence of NiCl(2)(dppe) gave only the unsaturated beta-C-phenylglycoside 2abeta, while palladium-catalyzed reaction led to the preponderant formation of C-phenylglycoside 2aalpha. Reaction of PhMgBr with p-tert-butylphenyl 4-O-benzyl-2,3,6-trideoxy-alpha-L-erythro-hex-2-enopyranoside (20) afforded stereospecifically the unsaturated alpha- and beta-C-phenylglycoside 25 in the presence of PdCl(2)(dppf) and NiCl(2)(dppe), respectively.