Synthesis of N-methyl-d-ribopyranuronamide nucleosides

Abstract

a b s t r a c tThe synthesis of N-methyl-D-ribopyranuronamide nucleosides is described. The key route is the rearrangement of a 1,2-O-isopropylidene protected furanose sugar with a carboxamide function in the 4-position to a ribopyranuronamide ring. The Lewis acid catalyzed condensation of adenine and thymine nucleobases with the per-O-acetylated N-methyl-D-ribopyranuronamide sugar is used to give the target nucleosides as a mixture of the a and b anomers. The mixture was separated and the final compounds were obtained by deacetylation in basic conditions.

The synthesis of piperidine nucleoside analogs—a comparison of several methods to access the introduction of nucleobases

“…N-methyl-D-ribopyranuronamide nucleosides 10aeb and 11aeb were synthesized and evaluated in antiviral and cytotoxic assays, however, no activity was found. 25,26 Piperidine nucleoside 12 was prepared by Kim et al, 27 and it seemed that oligonucleotides containing this modification exhibited a strong hybridization with RNA depending on the location and number of substitutions. Also, the increase of hydrophobicity in these modified oligonucleotides can be advantageous for cellular uptake.…”

The Synthesis and Conformation of Dihydroxypiperidinyl Derivates of Nucleobases as Novel Iminosugar Nucleoside Analogs

“…[15] N-Methyld-ribopyranuronamide nucleosides 13a-b and 14a-b were synthesized and evaluated in antiviral and cytotoxic assays, however, no activity was found. [16][17] Piperidine nucleoside 15 was prepared by Kim et al, [18] and it seemed that oligonucleotides containing this modification exhibited a strong hybridization with RNA counterparts, depending on the location and number of substitutions. Furthermore, it was suggested that the increase of hydrophobicity in these modified oligonucleotides can be advantageous for cellular uptake.…”

An Update Mini-Review on the Progress of Azanucleoside Analogues

“…It is worth mentioning that the endocyclic nitrogen atoms of N-azanucleosides are conveniently protected since the N, N-acetals in N-azanucleosides, such as aza-thymidine (Figure 1), are prone to spontaneous hydrolysis. 11,[13][14][15][16][17][18][19] However, glycosidic C-C bonds are resistant to acidcatalyzed and enzymatic hydrolysis, making C-azanucleosides more stable. 20) In some cases, azaribofuranosyl moieties are replaced by chains containing nitrogen atoms, and these molecules are termed acyclic azanucleosides, such as aza-analogue of acyclovir (Figure 1).…”