Synthesis Of Novel Nucleoside Analogues Research Articles

Design and Synthesis of Bicyclo[4.3.0]nonene Nucleoside Analogues.

Nucleoside analogues are effective antiviral agents, and the continuous emergence of pathogenic viruses demands the development of novel and structurally diverse analogues. Here, we present the design and synthesis of novel nucleoside analogues with a carbobicyclic core, which mimics the conformation of natural ribonucleosides. Employing a divergent synthetic route featuring an intermolecular Diels-Alder reaction, we successfully synthesized carbobicyclic nucleoside analogues with high antiviral efficacy against respiratory syncytial virus.

An expeditious synthesis of novel DNA nucleobase mimics of (+)-anisomycin

A glycal based expeditious synthesis of novel nucleoside analogues of (+)-anisomycin is reported. Readily available tri-O-benzyl-D-glucal was converted to a partially protected trihydroxypyrrolidine that is used as a common scaffold for the introduction of various nucleobases at the primary hydroxyl centre. Nucleoside analogues possessing all four DNA bases have been synthesized. Selective acetylation at C3 position was carried out with two of these unnatural nucleosides in order to mimic the structure of (+)-anisomycin. Cytotoxicity studies of some of these nucleosides showed that they display weaker activity on HeLa cells than Ara-C.

Diastereoselective Synthesis of Arabino- and Ribo-like Nucleoside Analogues Bearing a Stereogenic C3' All-Carbon Quaternary Center.

The synthesis of novel nucleoside analogues bearing a C3' all-carbon quaternary center and a C2'-hydroxy substituent is described. The all-carbon stereogenic center was generated through an intramolecular 7-endo attack of a silyl-tethered allyl moiety on a tertiary radical using photoredox catalysis. Subsequent allylic oxidation and diastereoselective hydride reductions provided the hydroxy substituent at C2', which then controls the stereoselective introduction of pyrimidine nucleobases on the corresponding furanose scaffold. Density functional theory (DFT) calculations provided insights into the origin of the high syn diastereoselectivity resulting from the radical cyclization. This original methodology grants access to a wide range of 1',2'-cis and 1',2'-trans arabino- and ribo-like analogues bearing an all-carbon quaternary center at C3'. These molecules are currently being tested for their antiviral and anticancer properties.

ChemInform Abstract: Multicomponent Reactions in Nucleoside Chemistry

AbstractReview: 126 refs.

Multicomponent reactions in nucleoside chemistry.

This review covers sixty original publications dealing with the application of multicomponent reactions (MCRs) in the synthesis of novel nucleoside analogs. The reported approaches were employed for modifications of the parent nucleoside core or for de novo construction of a nucleoside scaffold from non-nucleoside substrates. The cited references are grouped according to the usually recognized types of the MCRs. Biochemical properties of the novel nucleoside analogs are also presented (if provided by the authors).

Synthesis of 5-(2-Hydroxybenzoyl)-1,3-Disubstituted Uracils

A new synthesis of novel nucleoside analogues is reported. These 5-(2-hydroxybenzoyl)-1,3-disubstituted uracils have been prepared by the coupling of chromone-3-carboxylic acid with carbodiimides, leading to 3-chromone- N -acylureas, which underwent organocatalyzed N-cyclization and chromone ring opening. In the case of ditolylcarbodiimide, the corresponding uracil was obtained by a one-pot, uncatalyzed reaction with chromone-3-carboxylic acid.

Study of the Endocyclic versus Exocyclic C–O Bond Cleavage Pathways of α- and β-Methyl Furanosides

The activation and ring-opening of methyl furanosides in the four natural sugar scaffolds (ribo, lyxo, arabino, and xylo) efficiently afforded acyclic thioacetals with high S(N)2-like selectivity at the acetal center in the presence of Me2BBr and thiophenol. The stereochemical outcome of these reactions provides important mechanistic insights into the activation pathway of five-membered semicyclic acetals. The thioacetal products should find applications in oligosaccharides synthesis and allow further development of acyclic strategies for the synthesis of novel nucleoside analogues.

Preparation of both enantiomers of a synthon for novel nucleoside analogs by enzymatic desymmetrization of a meso-diol with a methylene cyclopropane skeleton

The enzymatic desymmetrization of methylenecyclopropane diol or its corresponding diacetate derivative, generated from a [2+1] cycloaddition between dioxepin and methylchlorocarbene, is described. After screening five commercial lipases, the two enantiomers of acetic acid 2-hydroxymethyl-3-methylene-cyclopropylmethyl ester are obtained in high yields and excellent enantioselectivities by using PFL or LPP in organic solvent. The stereostructure of the desymmetrization products was established by X-ray analysis. We also reported a new example with this non racemic chiral building block where the sign of optical rotation is dramatically solvent dependent and inverted. Using these enantiopure building blocks, a synthesis of novel nucleoside analogs is also presented.

Synthesis of Novel Nucleoside Analogues Based on 1,3‐Dihydrobenzo[c]furan Core.

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Synthesis of Novel Nucleoside Analogues Based on 1,3‐Dihydrobenzo[c]furan Core

AbstractA novel efficient synthetic route to 1,3‐dihydrobenzo[c]furan glycone was developed and the corresponding 5‐fluoro, 5‐iodo uracil and guanosine derivatives, the aromatic analogues of the well known antiviral 2′,3′‐dideoxy‐2′,3′‐dihydronucleosides (d4N), were synthesized.