Homo-C-nucleoside analogs IV. Synthesis of 4-(2,5-anhydro-D-altro-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole homo-C-nucleoside. CD assignment of the absolute configuration of the carbon bridge.
Dehydrative cyclization of 4-(D-altro-pentitol-1-yl)2-phenyl-2H-1,2,3-triazole in basic medium with one moler equivalent of p-toluene sulfonyl chloride in pyridine solution gave the homo-C-nucleoside 4-(2,5-anhydro-D-altro-1-yl)-2-phenyl-2H-1,2,3-triazole. The structure and anomeric configuration was determined by acylation, nuclear magnetic resonance (NMR), and mass spectroscopy. The stereochemistry at the carbon bridge of homo-C-nucleoside 2-phenyl-2H-1,2,3-triazoles was determined by circular dichroism (CD) spectroscopy.
Circular dichroism as a reliable tool for anomeric assignment of glycosyl-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs. A rule for prediction of their anomeric configuration.
The circular dichroism (CD) of a series of acyclic C-nucleoside analogs; 4-(pentahydroxypentyl-1-yl)-2-phenyl-2H-1,2,3-triazoles [1-5] and 4-(D-glycero-D-gulo)-2-phenyl-2H-1,2,3-triazole 6, are reported. A correlation between the sign of the Cotton effect at the maximal UV absorption and the absolute configuration of the carbon atom alpha- to the triazole base moiety is reported. The CD of anomeric 4-(alpha,beta-D-arabinofuranosyl)- and 4-(alpha,beta-D-arabinopyranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleosides are reported. The assignment of the anomeric configuration of C-glycosyl-2-phenyl-2H-1,2,3-triazoles from their CD spectra was found to be a simple method that relies on comparison of the sign of the Cotton effect at the maximal UV absorption and the absolute configuration of the anomeric carbon atom. A correlation between the anomeric configuration and the sign of the Cotton effect at the maximal UV absorption is deduced and generalized as a rule for prediction of the anomeric configuration of C-glycosyl-2-phenyl-2H-1,2,3-triazoles. Nuclear Overhauser effect and 13C NMR spectra supported the CD assignment rule.
Pyrimidine homonucleoside analogues from 2,5-anhydroaldose derivatives
Abstract 3,4-Di- O -acetyl-2,5-anhydro- D -xylose diisobutyl dithioacetal ( 1 ) reacts with bromine to give a monobromo derivative which, on condensation with 2,4-diethoxy-pyrimidine or its 5-methyl analogue, affords the protected nucleoside derivatives 4 and 11 , respectively; ammonolysis of 4 gave the cytosine “homonucleoside” 7 , and hydrolysis of 11 gave the thymine “homonucleoside” 12 . The same type of “homonucleoside” may be produced by cyclization of the sugar chain in a suitable acyclic-sugar nucleoside, as in the conversion of 1- S -ethyl-1-thio-1-(uracil-1-yl)- D -xylitol ( 16 , obtained from tetra- O -acetyl- D -xylose diethyl dithioacetal, 9 ), by the action of one molar equivalent of p -toluenesulfonyl chloride, into a homonucleoside isolated as its diacetate 17; acyclic-sugar derivatives not susceptible to such cyclization afford instead the 5- p -toluenesulfonates, as exemplified by the conversion of the D - arabino analogue ( 13 ) of 16 into the 5′-ester 14 . When cyclohexene is used to remove the excess of bromine in the preparation of nucleoside analogues from dithioacetals, the alkylsulfenyl bromide produced may react, by way of its cyclohexene adduct, with the hoterocyclic base to give cyclohexane-base adducts, for example, compounds 6 and 10 .