J. Rozenski

Use of Cyclohexene Epoxides in the Preparation of Carbocyclic Nucleosides

Abstracts A simple route towards 4,4-dihydroxymethyl-cyclohexane nucleosides has been developed. The structure of 4,4-dihydroxymethyl-1-(thymin-1-y1)-cyclohexane was confirmed by X-ray analysis. The synthesized compounds were inactive against all viruses tested.

Synthesis, enzymatic stability and physicochemical properties of oligonucleotides containing a N-cyanoguanidine linkage.

Abstract Nucleoside dimers with a N-cyanoguanidine linkage were synthesized and used as building blocks for oligonucleotide synthesis. Oligonucleotides composed of alternating phosphodiester and cyanoguanidine functions are still able to hybridize with a complementary natural oligodeoxynucleotide.

2′-Deoxyuridines with a 5-Heteroaromatic Substituent: Synthesis and Biological Evaluation

A series of novel 2′-deoxyuridines with a thienyl substituent in the 5-position were synthesized as potential anti-HSV-1 agents. The brominated derivatives (1d, 1e and 3b) were obtained via halogenation reactions of the protected 5-(thien-2-yl)-2′-deoxyuridine and 5-(thien-3-yl)-2′-deoxyuridine, respectively. The palladium-catalysed cross-coupling reaction with stannylated thiophene was used for the synthesis of (E)-5-(2-thienylvinyl)-2′-deoxyuridine and 5-(5,2′-dithien-2-yl)-2′-deoxyuridine. These compounds show moderate to good activity against herpes simplex virus type 1 (HSV-1) in the order of decreasing activity 1d>4>1e>3b∼5. Finally, two substituted 5-isoxazol derivatives of 2′-deoxyuridine (6a and 6b) were obtained via a 1,3-dipolar cycloaddition of the protected 5-ethynyl-2′-deoxyuridine. These new compounds demonstrated poor affinity for the virus-specific enzyme thymidine kinase.

Synthesis of N-6-alkylated adenosine derivatives

Abstract N 6-ablated adenosine can be synthesized by reduction of the corresponding carboxylic acid amides using Lm. Starting from 2′,3′-O-isopropylidene adenosine, N 6-ethyladenosine, N 6-propyladenosine, N 6-isobutyladenosine, N 6-benzyladenosine and N 6-furfuryladenosine were obtained in a three step procedure (acylation, reduction, deprotection).

Increased RNA affinity of HNA analogues by introducing alkoxy substituents at the C-1 or C-3 position

1,5-Anhydrohexitol nucleoside congeners with alkoxy substituents, were prepared, resulting in a further improvement of their RNA affinity and antisense potential.

2-Hydroxyethoxyethylated Bases as Acyclic Analogues of 1,5-Anhydrohexitol Nucleoside Derivatives

Abstract The synthesis and antiviral activity of a new series of acyclic nucleoside analogues containing a (2-hydroxyethoxy)ethyl moiety is discussed.

Mixed oligonucleotide analogues with an acyclic carbohydrate moiety and a N-cyanoguanidine functionality

Abstract Mixed aligonucleotide analogues having a backbone structure with a N-cyanoguanidine functionality and an acyclic sugar moiety were synthesized. This combination, however, has a detrimental effect on duplex stability of DNA-DNA hybrids.

The N-1-(3'-deoxythymidin-3'-yl)-N-2-cyano-N-3-(5'-deoxythymidin-5'-yl) guanidine dimeric building block in automated DNA synthesis and mass spectrometric analysis of its integrity

Nucleoside dimers with an N-cyanoguanidine linkage were synthesized and incorporated in oligonucleotides on an automated DNA synthesizer. The integrity of the dimer was investigated using mass spectrometry.

Methylated hexitol nucleic acids, towards congeners with improved antisense potential.

Abstract In an effort to further improve the hybridisation potential of anhydro-hexitol nucleoside analogues, the 1′-methoxyl and 3′-methoxyl substituents were introduced and evaluated for their antisense potential. In view of the selectivity of pairing with RNA, especially the introduction of a 3′-O-alkyl moiety deserves further study.