4-deoxy Analogs Research Articles

Specificity of acceptor binding to Leuconostoc mesenteroides B-512F dextransucrase: Binding and acceptor-product structure of α-methyl- d-glucopyranoside analogs modified at C-2, C-3, and C-4 by inversion of the hydroxyl and by replacement of the hydroxyl with hydrogen

The specificity of acceptor binding to the active site of dextransucrase was studied by using α-methyl- d-glucopyranoside analogs modified at C-2, C-3, and C-4 positions by (a) inversion of the hydroxyl group and (b) replacement of the hydroxyl group with hydrogen. 2-Deoxy-α-methyl- d-glucopyranoside was synthesized from 2-deoxyglucose; 3- and 4-deoxy-α-methyl- d-glucopyranosides were synthesized from α-methyl- d-glucopyranoside; and α-methyl- d-allopyranoside was synthesized from d-glucose. The analogs were incubated with [ 14C]sucrose and dextransucrase, and the products were separated by thin-layer chromatography and quantitated by liquid scintillation spectrometry. Structures of the acceptor products were determined by methylation analyses and optical rotation. The relative effectiveness of the acceptor analogs in decreasing order were 2-deoxy, 2-inverted, 3-deoxy, 3-inverted, 4-inverted, and 4-deoxy. The enzyme transfers d-glucopyranose to the C-6 hydroxyl of analogs modified at C-2 and C-3, to the C-4 hydroxyl of 4-inverted, and to the C-3 hydroxyl of 4-deoxy analogs of α-methyl- d-glucopyranoside. The data indicate that the hydroxyl group at C-2 is not as important for acceptor binding as the hydroxyl groups at C-3 and C-4. The hydroxyl group at C-4 is particularly important as it determines the binding orientation of the α-methyl- d-glucopyranoside ring.

Culcitosides C2 and C3 from the starfishCulcita novaeguineae

Two steroid glycosides not previously described have been isolated from the digestive system of the starfishCulcite novaeguiniae, and these have been called culcitosides C2 and C3. With the aid of chemical and spectral methods, the chemical structure of C2 has been established as 24ξ-methyl-5α-cholestane-3β,4β,6α,8,15β,16β,28-heptaol 28-O-[O-(2,4-di-O-methyl-β-D-xylopyranosyl)-(1 → 2)-α-L-arabinofuranoside, and that of C3 as its 4-deoxy analogue.

C-nucleoside studies. Part 17. The synthesis of 3(5)-carbamoyl-5(3)-β-Dribofuranosylpyrazole (4-deoxypyrazofurin) and 4-amino-3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole

4-Amino-3(5)-cyano-5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (10) was converted into the diazopyrazole (11) by treatment with nitrous acid. On photolysis in aqueous dioxane using visible light compound (11) gave 3(5)-cyano–5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (12)[48% from (10)] which formed the corresponding amide (13)(75%) with alkaline hydrogen peroxide. Deprotection of compound (13) with methanolic ammonia afforded 3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole (4)(74%), the 4-deoxy analogue of pyrazofurin (3).3(5)-Cyano-4-nitro-5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (1) reacted with dihydropyran and toluene-p-sulphonic acid to give the N-tetrahydropyranyl derivative (21)(66.5%). Hydrolysis of the nitrile group of compound (21), using alkaline hydrogen peroxide, afforded the amide (22)(71%) which was deprotected to give 3(5)-carbamoyl-4-nitro-5(3)-β-D-ribofuranosylpyrazole (23)(83%). Catalytic reduction of compound (23) gave 4-amino-3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole (5)(83%) which could be converted into formycin B (24)(69%).

Synthesis of analogs of methyl β- D-galactopyranoside modified at C-4

Syntheses are reported of 4-substituted, 4-deoxy analogs of methyl β- D-galactopyranoside (the 4-amino-4-deoxy, 4-azido-4-deoxy, 4-bromo-4-deoxy, 4-chloro-4-deoxy, 4-deoxy-4-fluoro, 4-deoxy-4-iodo, and 4-thio derivatives) as potential substrates of D-galactose oxidase. These syntheses involved nucleophilic displacement of the 4-( p-bromophenylsulfonyl)oxy group of appropriate D-glucose derivatives, although the more reactive (trifluoromethylsulfonyl)oxy group was also utilized as a novel leaving-group. Formation of the bromo and iodo derivatives was accompanied by appreciable halogen exchange and a resulting overall retention of configuration, and formation of the thio compound was attended by competing reactions. Optical rotatory characteristics of the halogeno compounds, their triacetates, and tribenzoates are described, and “anomalous” behavior of the last group is noted.

A non-hydrogen-bonding role for the 4-hydroxyl group of D-Galactose in its reaction with D-Galactose oxidase

Several 4-deoxy analogs of methyl β- D-galactopyranoside are oxidized by D-galactose oxidase. The rates associated with their various, axially attached 4-substituents follow the sequence OH>NH 2>F⪢>Cl> H; these differences are attributed mainly to variations in K m . Other 4-deoxy analogs, namely, the 4-azido-4-deoxy, 4-bromo-4-deoxy-, 4-deoxy-4-iodo, and 4-thio derivatives were found to be inactive. These observations indicate that the axial 4-hydroxyl group of D-galactopyranose does not play a hydrogen-bonding role primarily, but constitutes a substituent of a size optimal for interaction with the enzyme.