Highly diastereoselective synthesis of modified nucleosides via an asymmetric multicomponent reaction

The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2’-O positions of the viral RNA cap (GpppA-RNA→m7GpppA-RNA→m7GpppAm-RNA), using S-adenosyl-L-methionine (SAM) as a methyl donor. We report here the synthesis and biological evaluation of a series of novel nucleoside analogs. Two of these compounds can effectively and competitively inhibit the WNV MTase with IC50 values in micromolar range and, more importantly, do not inhibit human MTase. The compounds can also suppress the WNV replication in cell culture.

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“…The nucleoside analogs were synthesized as previously described (Ghosh and Kass, 2010). Sinefungin (SIN) was purchased from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs

et al. 2013

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“…In addition, adenine amides have widespread use in the multi-step synthesis of nucleosides or peptide nucleic acids (26). At the same time, adenine analogues exhibit highly desirable traits such as anti-cancer (27), anti-viral (28), anti-bacterial (29), anti-sense therapeutics (30) and anti-leukaemic (31) properties.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular synthons and pattern recognition in adenine amides – synthesis, structures and thermal properties

Adamski

Bogucki

S̀wietlik

et al. 2015

Supramolecular Chemistry

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An effective method for the synthesis of novel adenine amides was developed and successfully implemented, leading to 4-propyloxy-N-(9H-purin-6-yl)benzamide (1) and 4-dodecyloxy-N-(9H-purin-6-yl)benzamide (2). The compounds were fully characterised by means of spectroscopic ( 1 H NMR, 13 C NMR, FT-IR) and thermal (TG, DSC) analysis. The crystallographic analysis revealed that the formation of supramolecular chains relies on hydrogen bonding between amide functionalities. All supramolecular synthons found in the crystal structure of 1 were confirmed with the temperature-dependent IR method. The temperature-dependent IR method is useful in determining supramolecular interactions for compound 2, for which the crystal structure could not be obtained. A detailed analysis of temperature-dependent FT-IR spectra was used for the first time to identify the hydrogen bonds that exist in the solid state of our compounds; it can therefore be considered a promising method for the pattern recognition of hydrogen bonding in supramolecular chemistry.

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“…1). 14 Since carbohydrates have high degree of functionalization they can be used as templates by linking different active ends such as -NH 2 , -CN, -COOH, -NC, -N 3 and multiple bonds etc. For instance modied nucleosides 4 and 5 were synthesized by combination of optically active dihydrofuran, ethyl acetoacetate and corresponding substituted bis(trimethysilyl)thymine (Fig.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in multicomponent reactions involving carbohydrates

2015

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Being an attractive class of naturally occurring molecules with fascinating properties sugars and their derivatives have wide applications in different fields especially in drug discovery. Due to their highly diverse nature they play various important key roles in biological systems. In terms of providing both desirable structural diversity and compound libraries, multicomponent reactions (MCRs) are most efficient strategies. MCRs are widely employed by chemists to generate sugar based derivatives with significantly extended variations having various benefits to society. The advances in the synthesis of structurally diversified sugar based derivatives through new MCRs of the previous decade are reviewed. Scheme 2 Ugi-MCR based synhesis of divalent neoglycoconjugates where diacid acting as bridge. Scheme 3 Four component synthesis of N-glycosyl-Asp-urea conjugate. Scheme 4 Multicomponent reaction with symmetric and asymmetric carbodiimide. 57886 | RSC Adv., 2015, 5, 57883-57905 This journal is Scheme 13 Synthesis of thiosugar annulated dihydropyrimidines 63 and 64. Scheme 14 Complementry Mannich and Reformatsky route for the synthesis of C-glycosyl aminoesters. Scheme 15 Synthesis of furanose C-nucleoside enantiomer 75 and 76 via Hantzsch reaction. 57890 | RSC Adv., 2015, 5, 57883-57905 This journal is Scheme 26 Multicomponent synthesis of polyhydroxyl thiomidazoles from aldoses and ketoses.Fig. 6 Synthesised polyhydroxy imidazoles using different aldoses and ketoses. Scheme 27 Multicomponent synthesis of annulated pyrroles in choline chloride : urea (CC/U). Scheme 28 Multicomponent synthesis of sugar derived triaozolodiazepine. 57894 | RSC Adv., 2015, 5, 57883-57905 This journal is Scheme 36 Total synthesis of (À) muramycin D 2 Ugi based multicomponent reaction. Scheme 37 Ugi-4CR synthesis of trypsin-CMC and trypsin-ALG conjugate. This journal is Scheme 41 Three component sequential synthesis of glyco-hydantoin conjugates. Scheme 42 Mechanism showing the favourable O-N acyl migration and slow intramolecular aza-Micheal step. Scheme 43 Conversion of glyco-hydantoin conjugates into sugar-pseudopeptide. Scheme 44 Synthesis of sugar lactone fused spiropyrrolizidine oxindole. 57902 | RSC Adv., 2015, 5, 57883-57905 This journal is

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Highly diastereoselective synthesis of modified nucleosides via an asymmetric multicomponent reaction

Abstract: We have developed a practical synthesis of unique nucleoside derivatives via TiCl4 promoted multicomponent reaction of optically active dihydrofuran, ethyl pyruvate/glyoxylate, and a TMS protected nucleobase in a single-pot operation.

Cited by 12 publications

References 21 publications

Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs

Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs

Supramolecular synthons and pattern recognition in adenine amides – synthesis, structures and thermal properties

Recent advances in multicomponent reactions involving carbohydrates

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