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Suitably protected (R)‐ and (S)‐HPEP {9‐[3‐hydroxy‐2‐(phosphonoethoxy)propyl]} derivatives containing adenine and thymine nucleobases were prepared as monomers for the introduction of acyclic nucleotide units into oligonucleotides. The solid phase synthesis of a series of ribo and 2′‐deoxyribo nonamers containing (R)‐HPEP and (S)‐HPEP units was successfully performed in both 5′ → 3′ and 3′ → 5′ directions. The measurement of thermal characteristics of the complexes of modified nonamers with complementary DNA and RNA strands revealed a general destabilizing effect of the introduced acyclic units on the thermal stability, but in several cases [modif.RNA*RNA and modif.DNA*RNA with (S)‐HPEPA units], the duplexes were characterized in terms of Tm values. A solid‐phase synthesis afforded a series of ribo and 2′‐deoxyribo nonamers containing acyclic nucleotide units. A general destabilizing effect of the introduced acyclic units on the thermal stability of complexes of modified nonamers with the complementary DNA and RNA strands was observed, but in cases with (S)‐HPEPA units, the duplexes were characterized in terms of Tm values. [ABSTRACT FROM AUTHOR]

The lack of antiviral activity of recently described (S) -3-(adenin-9-yl)-2-(phosphonomethoxy)propanoic acid, or ( S )-CPMEA in brief, has been speculated to possibly be due to the increased hydrophilicity of the molecule and, thus, by its limited cellular permeability. Efficient syntheses of novel lipophilic prodrugs of ( S )-CPMEA masking either the carboxylic group or preferably both the phosphonate and carboxylic moieties, have been developed in order to increase bioavailability of the parent compound. Two prodrugs of ( S )-CPMEA, namely phosphonate bis-amidate 15 and phenyloxy amidate 16 , exhibited pan-genotypic anti-HCV activity at submicromolar concentrations. [ABSTRACT FROM AUTHOR]

An efficient route to acylated acyclic nucleosides containing a branched hemiaminal ether moiety is reported via three-component alkylation of N-heterocycle (purine nucleobase) with acetal (cyclic or acyclic, variously branched) and anhydride (preferentially acetic anhydride). The procedure employs cheap and easily available acetals, acetic anhydride, and trimethylsilyl trifluoromethanesulfonate (TMSOTf). The multi-component reaction is carried out in acetonitrile at room temperature for 15 min and provides moderate to high yields (up to 88%) of diverse acyclonucleosides branched at the aliphatic side chain. The procedure exhibits a broad substrate scope of N-heterocycles and acetals, and, in the case of purine derivatives, also excellent regioselectivity, giving almost exclusively N-9 isomers. [ABSTRACT FROM AUTHOR]