Preparation of 6-azafulleroid-6-deoxy-2,3-di-O-myristoylcellulose

6-Azafulleroid-6-deoxy-2,3-di-O-myristoylcellulose (3) was synthesized from 6-azido-6-deoxycellulose (1) by two reaction steps. The myristoylation of compound 1 with myristoyl chloride/pyridine proceeded smoothly to give 6-azido-6-deoxy-2,3-di-O-myristoylcellulose (2) in 97.0% yield. The reaction of compound 2 with fullerene (C₆₀) was carried out by microwave heating to afford compound 3 in high yield. It was found from FT-IR, ¹³C NMR, UV–vis, differential pulse voltammetry (DPV), SEC analyses that compound 3 was the expected C₆₀-containing polymer. Consequently, maximum degree of substitution of C₆₀ (DS_C60) of compound 3 was 0.33.     

Preparation of 3-deoxy-3-deuteroestrone and 3-deoxy-4-14C-estrone

3-Deoxy-3-deuteroestrone (1,3,5(10)-estratrien-17-one-3-d) and 3-deoxy-4-¹⁴C-estrone (1 ,3 ,5(10)-estratrien-17-one-¹⁴C) have been prepared. The mechanism of reductive dehalogenation of aryl iodides with lithium aluminum deuteride is discussed. The ¹³C-NMR spectrum of 3-deoxy-3-deuteroestrone is discussed.     

Synthesis of 6-deoxy-5-thio- -glucose

Three routes were investigated for the conversion of -glucose into the title compound. In the first approach, reduction of the 5,6-thürane ring of 5,6-dideoxy-5,6-epithio-1,2-O-isopropylidene α- -glucofuranose (17) as well as that of its 3-O-allyl derivative (13) with lithium aluminium hydride was investigated; 17 afforded the corresponding 6-deoxy derivative besides di-, tri-, and poly-mers, whereas only polymers were formed from 13. In the second approach, the oxirane ring of

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was reduced by sodium borohydride and the resulting 6-deoxy derivative was converted into the 5-thiobenzoate; the corresponding hex-4-enofuranose was formed as a byproduct. In the third approach partial mesylation of methyl 5-thio-α- -glucopyranoside was attempted, but the 6-mesylate 27 could be isolated only in modest yield (28%) together with rearranged 2,5-thioanhydromannofuranoside derivatives. The mechanism of this rearrangement is discussed in detail. The 6-mesylate 27 was converted via the 6-iodo derivative into the title compound.     

Synthesis and structural analysis of 6-deoxy-6-hydroxyphosphinyl-D-fructopyranose derivatives

3,4-Di-O-benzyl-6-deoxy-6-diethoxyphosphinyl-1,2-O-isopropylidene-beta-D-fructofuranose (13) was prepared from the known 1,2-O-isopropylidene-6-O-tosyl-beta-D-fructofuranose in five steps. Reduction of 13 with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the 6-deoxy-6-hydroxyphosphinyl-D-fructopyranose derivative. This was converted into the 1,2,3,4,5-penta-O-acetyl-6-deoxy-6-methoxyphosphinyl-D-fructopyranoses, whose structure and conformation were established by 1H NMR spectroscopy.     

Synthesis of 6-deoxy-6-chloro and 6-deoxy-6-bromo derivatives of scleroglucan as intermediates for conjugation with methotrexate and other carboxylate containing compounds

Polysaccharides are widely used as carriers in the field of drug delivery. We present a methodology to obtain water soluble drug-conjugates based on scleroglucan. Selective C-6 halogenation gives access to C-6 esters; conjugates between methotrexate and scleroglucan are described, potentially useful for antitumour therapy or in rheumatoid arthritis treatment.     

Synthesis and stereochemistry of 6-deoxy-6-halogeno-D-glucofuranose cyclic phosphates.

1, 2-O-Cyclohexylidene- and 1, 2-O-isopropylidene-alpha-D-glucofuranose react with hexa-alkylphosphorous triamides to give the corresponding 3, 5, 6-phosphites. Treatment of the latter compounds with chlorine and bromine affords 1, 2-substituted 6-deoxy-6-halogeno-alpha-D-glucofuranose 3, 5-phosphorohalogenidates. Replacement of halogen at phsophorus by hydroxyl and amino groups has been investigated. Cyclic phosphorohalogenidates isomerize in N, N-dimethylformamide. The stereochemistry of the compounds investigated was established by using 1H- and 13C-n.m.r. data.     

The action of Bacillus subtilis liquefying amylase on 6-deoxy-6-iodoamylose

Benzyl 2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-glucopyranoside (1) was chosen as a model bioside to develop a standard procedure for the selective cleavage of glycosidic linkages in polysaccharides containing 2-amino-2-deoxyhexose residues. Treatment of 1 with hydrazine in the presence of hydrazine sulphate resulted in quantitative N-deacetylation with the formation of benzyl 2-amino-2-deoxy-3-O-β-D-galactopyranosyl-α-D-glucopyranoside (2). The galactosyl glycosidic linkage in 2 could be selectively cleaved by acid hydrolysis. Oxidation of 2 with periodate destroyed the galactose residue. Treatment of 2 with nitrous acid cleaved the 2-amino-2-deoxy-D-glucosyl linkage to give 2,5-anhydro-3-O-β-D-galactopyranosyl-D-mannose (3) and benzyl alcohol.     

Preparation of glycosides of 2-deoxy-2-methylamino-D-mannose, 2-deoxy-2-methylamino-D-glucose,and 2-deoxy-2-methylamino-D-galactose: observations on N-methylation of amides

Benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-α-D-mannopyranoside (10) and its furanose isomer (9), the derived N-methyloxazolidinones 11 and 6, benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-β-D-glucofuranoside (15) and methyl 2-deoxy-2-methylacetamido-β-D-galactofuranoside (20), were prepared from appropriate diethyl dithioacetals. They were considered the most suitable starting materials for synthesis of O-methyl-2-deoxy-2-methylamino-hexoses because of their ease of preparation and the presence of suitable blocking groups. Oxazolidinones were prepared from N-benzyloxycarbonyl derivatives of 2-amino-2-deoxy-D-mannose by using methanolic sodium methoxide. Their use in preparation of 2-deoxy-2-methyl-amino derivatives is discussed. The Kuhn reagent was used in these syntheses for N-methylating amides. However, certain amides containing comparatively bulky substituents in the vicinity of the NH group are resistant to methylation.     

Transport of 4-deoxy- and 6-deoxy-D-glucose in baker's yeast

Tritium-labelled 4-deoxy-D-glucose (4-dglc) and 6-deoxy-D-glucose (6-dgcl) were prepared by catalytic hydrogenolysis of the corresponding deoxyiodo derivatives with gaseous tritium. The two sugars are transported into Saccharomyces cerevisiae by both the constitutive glucose and the inducible galactose carrier. Uranyl ions are powerful inhibitors. The pH optimum in uninduced cells lies at 5.5 for both sugars, the apparent activation energies (between 15 and 35 degrees C) are 25.1 kJ/mol and 16.5 kJ/mol, respectively. The steady-state intracellular concentration of both sugars is less than the extracellular one (no uphill transport). Neither of them is a substrate of yeast hexokinase. 4-Deoxy-D-glucose undergoes a dinitrophenol-sensitive conversion to an unknown metabolite which is not phosphorylated and may represent one of its oxidation products.     

New 6-butylamino-6-deoxycellulose and 6-deoxy-6-pyridiniumcellulose derivatives with highest regioselectivity and completeness of reaction

This paper investigates the nucleophilic substitution (S(N)) reactions of tosylcellulose with butylamine and pyridine, respectively. The S(N) reactions of tosylcellulose 1 (DS(Total) 2.02; DS(C-6) 1.0) with butylamine carried out at 25, 50, 75 and 100 degrees C in both dimethyl sulfoxide (DMSO) and pure butylamine showed that the regioselectivity of substitution at C-6 of cellulose is temperature dependent: the highest regioselectivity at C-6 can be reached at 25 and 50 degrees C; substitution at C-2 also occurred at 75 and 100 degrees C. The substitution speed in pure butylamine is greater than that in the presence of DMSO. A complete and regioselective substitution at C-6 with a DS of 1.0 was obtained under the conditions of 50 degrees C, 40 h in butylamine. The substitution reactions of 1 with pyridine carried out at 25, 50, 75 and 100 degrees C for 24h in DMSO did not occur. In contrast to this the S(N) reactions done in pure pyridine showed that a temperature- and steric-dependent, regioselective substitution took place at C-6 at temperatures from 25 to 145 degrees C. The highest regioselectivity and completeness at C-6 can be obtained at 100 degrees C for 90 h, whereas at 145 degrees C substitution also occurs at C-2. The results were proved by 1H NMR and 13C NMR spectroscopy.     

Studies on the substrate specificity of Taka-amylase A1. XIV. Preparation of 6-deoxy-6-halogenomaltotrioses and their hydrolysis by Taka-amylase A.

1. O-6-Deoxy-alpha-D-glucopyranosyl-(1 leads to 4)-O-alpha-D-glucopyranosyl-(1 leads to 4)-D-glucopyranose, O-6-chloro-6-deoxy-alpha-D-glucopyranosyl-(1 leads to 4)-O-alpha-D-glucopyranosyl-(1 leads to 4)-D-glucopyranose, O-6-bromo-6-deoxy-alpha-D-glucopyranosyl-(1 leads to 4)-O-alpha-D-glucopyranosyl-(1 leads to 4)-D-glucopyranose, and O-6-deoxy-6-iodo-alpha-D-glucopyranosyl-(1 leads to 4)-O-alpha-D-glucopyranosyl-(1 leads to 4)-D-glucopyranose were prepared, taking advantage of the substrate specificities of Taka-amylase A and glucoamylase, and the action of Taka-amylase A on these substrates was investigated. 2. The Michaelis constant Km and the molecular activity ko were determined at 37 degrees C and pH 5.2 using the modified maltotrioses. The values of Km and ko decreased upon modification of maltotriose and those of ko/Km were in agreement with the comparative initial rates for the corresponding derivatives of phenyl alpha-maltoside at low substrate concentrations. This result suggested that a subsite of the enzyme may have a specific interaction with halogen atoms in the substrate. 3. All halogenomaltotrioses examined showed substrate inhibition at high substrate concentrations.     

Solvolytic desulfation of 2-deoxy-2-sulfoamino-D-glucose and D-glucose 6-sulfate

Solvolytic desulfation of the pyridinium salts of 2-deoxy-2-sulfoamino-D-glucose and D-glucose 6-sulfate in dimethyl sulfoxide containing 5% of water or methanol was studied to develop a method for selective N-desulfation of heparin. The first-named salt was the most susceptible to N-desulfation.     

Purin-6-yl 6-deoxy-1-thio-beta-D-glucopyranoside. Enzymology, chemistry, and cytotoxicity

Purin-6-yl 6-deoxy-1-thio-beta-D-glucopyranoside (4) is a substrate for almond beta-glucosidase and a weak competitive inhibitor of bovine liver beta-D-glucuronidase (Ki approximately 20mM). Both 4 and purine-protonated 4 undergo hydrolysis catalyzed by dilute acid in the pH range 0.17-2.59. These results are compared with those previously obtained with ammonium (purin-6-yl 1-thio-beta-D-glucopyranosid)uronate, (purin-6-yl 1-thio-beta-D-glucopyranosid)uronamide, purin-6-yl 1-thio-beta-D-glucopyranoside, and purin-6-yl 2-deoxy-1-thio-beta-D-glucopyranoside, and it is concluded that the data support an involvement of substituents at C-5 in producing productive Michaelis-complex conformers. The 6-deoxyglucoside is more active than the D-glucosiduronic acid in an L1210 mouse screen.