The synthesis of cyclopropano nucleosides.

A tricyclic, fused cyclopropano nucleoside 8 containing a ketal group was synthesized by the one-pot seven sequential reactions of a trimesylated allofuranosyl adenine derivative 6 with Mg(OMe)2. When KOH was used instead of Mg(OMe)2, an alpha, beta-unsaturated ketonucleoside 7 was obtained.     

The synthesis of 2-pyrimidinone nucleosides and their incorporation into oligodeoxynucleotides.

The synthesis of 1-(beta-D-2'-deoxyribosyl)-2-pyrimidinone (dK) and its 5-methyl derivative (d5) from 2'-deoxycytidine or 2'-deoxythymidine, respectively, via silver oxide oxidation of 4-hydrazinopyrimidines is described. The necessary hydrazine substituted pyrimidine nucleosides have been prepared by transamination of a protected cytidine derivative or by addition/elimination reactions to an O4-sulfonated thymidine derivative. Oxidation of the 4-hydrazino pyrimidines was complicated by a competing hydrolytic reaction which generated 2'-deoxyuridine or 2'-deoxythymidine. However, in the presence of an organic base such as triethylamine, oxidation became the predominant reaction. After suitable protection and formation of the 3'-phosphoramidite derivatives, these modified nucleosides were incorporated into seven self-complementary oligodeoxynucleotides by chemical synthesis using phosphite triester methodology. Oligodeoxynucleotides were prepared such that dA-dT and dG-dC base pairs were substituted by dA-d5 or dG-dK base pairs, respectively. Both circular dichroism spectra and thermal denaturation studies were used to characterize the modified oligodeoxynucleotides.     

New approaches to the synthesis of antiviral nucleosides.

There is a pressing, worldwide need for new antiviral agents. The chemical synthesis of novel nucleosides for chemotherapeutic screening usually involves multistage processes which can be time consuming. The application of enzymatic methods for the synthesis and modification of antiviral nucleosides shows great promise because of the simplicity and high specificity of enzymatic reactions.     

The latest progress in the synthesis of carbocyclic nucleosides

This review presents the latest developments in the field of carba-nucleosides (1994-1998). Special attention is paid to the synthesis of key precursors to those carba-nucleosides that possess significant biological activities or have novel structures.     

The synthesis of [([beta-D-ribofuranosyloxy)methyl]nucleosides

The coupling reaction of acetoxymethoxy ribofuranoside 4 with nucleic acid bases 5a-f to synthesize novel (ribofuranosyloxy)methyl uracil, thymine, cytosine, adenine, guanine derivatives 6a-g respectively in preference to the expected formation of natural nucleosides 2',3',5'-tri-O-benzoyl uridine, methyluridine, cytidine, adenosine and guanosine 7a-g is described. Detailed study of these reactions catalysed by Lewis acids TMSOTf and SnCl4 is described. TMSOTf exhibited selectivity for the formation of ribofuranosyloxy methyl derivatives 6a-g rather than 7a-g. Reason for formation of 6a-g is explained by HSAB principle.     

Design and synthesis of novel fluorocyclopropanoid nucleosides

Novel fluorocyclopropanoid nucleosides were designed, synthesized and evaluated their antiviral activities against poliovirus, HSV, HIV, and HBV.     

Microbial synthesis of 2,6-diaminopurine nucleosides

2,6-Diaminopurine nucleosides are used as pharmaceutical drugs or prodrugs against cancer and viral diseases.

The synthesis of 2,6-diaminopurine riboside, -2′-deoxyriboside, -2′,3′-dideoxyriboside and -arabinofuranoside was efficiently carried out by transglycosylation using bacterial whole cells as biocatalysts. The preparation of 2,6-diaminopurine-2′,3′-dideoxyriboside catalysed by whole cells is here reported for the first time.