Search

A detailed comparison of the hybridisation characteristics of oligonucleotides with 4-hydroxy-N-acetylprolinol or 3-hydroxy-N-acetylprolinol as sugar substitute, reveals dramatic differences. The 4-HO oligonucleotides are able to form stable complexes which are in general duplexes when natural nucleic acids are used as the complement, and the system has a strong preference for isochiral interaction. For the 3-HO oligonucleotides on the other hand complexes are generally weak, triple stranded, and often isochiral and heterochiral hybrids have a similar stability. more...

A high yield synthesis of different O-ribofuranosylnucleosides has been achieved. Kinetics of the acid-catalysed hydrolysis of disaccharide nucleosides has been studied. Chemical and enzymatic incorporation of 2′-O-ribofuranosyl-nucleoside residue into oligonucleotides was investigated. more...

As part of a project concerning the investigation of new hexitol nucleic acids (HNA), the 1,5-anhydro-2-deoxy-D-altritol nucleoside building blocks with a uracil, cytosine, adenine and guanine base moiety were synthesized. The uracil analogue was used for the automated synthesis of corresponding oligonucleotides. Hybridization capabilities of these altritol nucleic acids (ANA) are illustrated by the Tm values obtained for the (a hU)13/(dA)13 duplex. more...

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). more...

2′, 5′-phosphodiester bond-linked oligoadenylate trimers with 3′-fluoro-3′-deoxyadenosine residues incorporated at specific positions of the nucleotide sequence were synthesized by the solid phase phosphite triester (phosphoramidite) method. The syntheses were in the 2′ to 5′ direction and were performed manually using commercially available microcolumns. The oligonucleotides were 5′-end phosphorylated on the support before deprotection. more...

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

A liquid chromatographic method was developed for the separation of thymidine from its anomer and isomers. The method was implemented during a comparative stability study of thymidine and 1- (2-deoxy-α-D-erythro-pentofurano-syl)thymine. more...

2′-Deoxy-2′-fluoro-D-arabinopyranosyl nucleosides were synthesized by condensation of 1,3,4-tri-O-benzoyl-2-deoxy-2-fluoro-D-arabinopyranose with the appropriate silylated bases in the presence of trimethylsilyl triflate. Scission of the 3′,4′-bond by periodate oxidation followed by sodium borohydride reduction resulted in the formation of the 3′,4′-seco analogues of the 2′-deoxy-2′-fluoro-D-arabinofuranosyl nucleosides. more...

The synthesis of pyrimidine nucleosides with a 2, 3, 4-tri-deoxy-D-glycero-hex-3-enopyranose, 2, 3, 4-trideoxy-D-glycero-hexopyranose, 2-deoxy-D-erythro-pentopyranose and 2-deoxy-2-fluoro-D-arabino-pentopyranose sugar moiety are described. more...

The title compound was prepared by reaction of the 5-bromo congener with potassium cyanide in DMF. X-ray analysis revealed its solid state structure and the obtained conformation was compared to the con-formation of 3′-azido-3′-deoxythymidine (AZT) and of 2′,3′-dideoxy-3′-fluoro-5-chlorouridine, respectively, two very selective anti-HIV agents. They both show two separate molecules in their asymmetric unit, one of each fairly resembling the conformation of the title compound 4. The latter, however, displayed only very moderate activity. more...

The preparation of ON derivatives with regiospecifically incorporated dialdehyde reactive groups and their successful use as affinity labels was described.

Nucleoside analogues with a 1,4-dioxane, 1,4-oxathiane or 1,4-oxazine ring structure were prepared from the corresponding dimesylated seconucleosides.

5-(Thien-2-yl)-2′-deoxyuridine, synthesized by coupling of 5-iodo-2′-deoxyuridine with 2-trimethylstannylthiophene in the presence of a Pd catalyst, shows potent anti-HSV-1 activity in vitro.

The synthesis of thymidine analogues with a N-cyanoimido substituent in the 3′- or 5′-position is described.

Dideoxycytidine analogues with a trideoxy-D-hexopyranosyl or hexenopyranosyl moiety were synthesized starting from 2-deoxyglucosyl bromide or tri-O-acetyl-D-glucal.

The synthesis and enzymatic stability of oligonucleotides with 1-(2, 3-dideoxy-β-D-erythro-hexopyranosyl) thymine and (S)-9-(3,4-dihydroxybutyl)adenine as monomeric units are described.

The phosphotriester method for synthesis of oligonucleotides has been used for evaluating silica with spacer groups. Three different spacers were synthesized of which a long chain alkylamine, a double glycine and a double y-aminobutyric acid unit. Only the double glycine spacer improved the yields of the first condensations and is now routinely used in our laboratory. more...

Reaction of O-protected xanthosines with p-nitrophenyl ethanol under Mitsunobu conditions yields the doubly alkylated O2,O6- and N1-,O2-derivatives. Deoxyxanthosine protected on both oxygens with a 2-(4-nitrophenyl)-ethyl group was synthesized starting from deoxyguanosine. Both protecting groups can be eliminated with DBU in pyridine. more...

The reaction of O-protected inosine with p-nitrophenyl ethanol under Mitsunobu conditions yields a mixture of the 1- and 0° -alkylated derivatives. 2′-Deoxyinosine protected on 06 -, can be synthesized fairly easy from deoxyguanosine with a Mitsunobu reaction followed by reductive deamination. more...

The mono- and diamino analogues of 9-(2-deoxy-α-D-erythro-pen-tofuranosyl)adenine la, 9-(2-deoxy-α-D-threo-pentofuranosyl)adenine 4a, 9-(3-deoxy-α-D-erythro-pentofuranosyl)adenine 2a and 9-(3-deoxy-α-D-threo-pentofuranosyl)adenine 3a were synthesized by triphenylphosphine reduction of the corresponding azido compounds. The azido group was introduced by a substitution reaction with lithium azide on mesylates or, more directly, by reaction with lithium azide, triphenylphosphine and carbon tetrabromide. Of the newly synthesized compounds, only 3′-amino-2′,3′-dideoxyadenosine proved, albeit slightly, inhibitory to murine leukemia L1210 and mammary carcinoma FM3A, and human B-lymphoblast Raji, T-lymphoblast Molt/4F and T-lymphocyte MT-4 cell proliferation in vitro (50 % inhibitory dose : 43.1-323 μM). None of the compounds inhibited human immunodeficiency virus-induced cytopathogenicity in MT-4 cells. more...

A survey is given of the different methods that have been used for the synthesis of nucleosides fluorinated in the carbohydrate moiety. In this article we describe the use of diethylaminosulfur trifluoride (DAST) as a fluorinating agent in the nucleoside field. more...

Successful incorporation of p-nitrophenylethyl protected deoxyino-sine and deoxyxanthosine and of deoxynebularine into oligonucleotides following a triester strategy, is demonstrated.