Considerable attention has been focused on the development of phosphonate-containing drugs for application in many therapeutic areas. However phosphonate diacids are deprotonated at physiological pH and thus phosphonate-containing drugs are not ideal for oral administration, an extremely desirable requisite for the treatment of chronic diseases. To overcome this limitation several prodrug struc...

Two gem-difluoromethylenated nucleoside moieties of liposidomycins, 3 and 4, were designed and synthesized. Compound 3 was assembled from lactol 5 and gem-difluoromethylenated nucleoside 6. In the synthesis of target molecule 4, the coupling of the trichloroacetimidate derivative of gem-difluoromethylenated furanose 7 with nucleoside 8 in the presence of TMSOTf gave the unexpected compound 16 w...

In order to assemble the sequence, addition of each nucleoside requires four chemical reaction steps and each of these reaction steps is expected to be quantitative (100%). In reality, efficiencies of these reaction steps vary from 97 to 99.9% depending on the reagents, nucleoside building blocks (phosphoramidite) and moisture in the solvent. Depending on the efficiency of each nucleoside addit...

Nucleoside diphosphokinase from Salmonella typhimurium has been purified and characterized. In many respects, the enzyme is similar to those from higher organisms in that it has a broad speciCcity for both phosphate donor and recipient and that it functions via a ping-pong mechanism. The enzyme activity of cells is very high at all growth rates but decreases as growth rate increases. Evidence i...

Novel 2'(β)-methyl-5'-deoxyapiose purine phosphonic acid analogues were designed and synthesized from 2-propanone1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbrüggen conditions. Condensation of aldehyde 14 with Wittig reagent [(diethoxyphosphinyl)methylidene] triphenylphosphorane gave the desired nucleoside phosphonate analogues 15. Ammonolysis and hydroly...

We are reporting on the synthesis of fluorescent nucleoside analogs with modified sugar moieties (e.g., sugars other than ribose and 2'-deoxyribose). Four novel derivatives of the fluorescent thymidine analog 6-methyl-3-(beta-D-2'-deoxyribofuranosyl) furano-[2,3-d]pyrimidin-2-one were synthesized via Sonogashira reaction and subsequent copper-catalyzed cycloaddition. These compounds represent p...

An investigational nucleoside analogue drug, viramidine, has recently emerged as a potentially safer alternative to ribavirin for the treatment of hepatitis C viral infection. We have reported that viramidine mainly functions as a prodrug of ribavirin that is enriched in the liver. This in vitro study further explores viramidine's activity against nucleoside phosphorylase, a host enzyme that is...

There are currently six approved nucleoside analogue reverse transcriptase inhibitors. Data are available from clinical trials in human pregnancy for zidovudine and lamivudine, while didanosine and stavudine are under study. Zalcitabine and abacavir have not been studied in pregnant women. Tenofovir disoproxil fumarate is the first acyclic nucleotide analogue reverse transcriptase inhibitor. Th...