Thienyl-Substituted Nucleosides and Their Triphosphates

Abstract

A series of thienyl-substituted nucleosides and their triphosphates has been prepared and the compounds evaluated as antiviral agents. The compounds investigated were 1-(5′-triphosphate-β-D-arabinofuranosyl)-5-(2″-thienyl)uracil (6), 1-(5′-triphosphate-β-D-arabinofuranosyl)-5-(2″-thienyl)cytosin (13) and 1-(5′-triphosphate-2′, 3′-dideoxynbofuranosyl)-5-(2″-thienyl)uracil (19). The activities of (6), (13) and (19) was shown to be inferior to that of the previously prepared compound 5-(2″-thienyl)-β-2′-deoxyuridine triphosphate (20).

Postsynthetic on Column RNA Labeling via Stille Coupling

“…Considering the strong dependence and sensibility of altered conditions and types of nucleobases, other Pd catalysts such as Pd(PPh 3 ) 2 Cl 2 [bis-(triphenylphosphine) palladiumdichloride], were applied for the reaction of 2-iodo adenosine 1 with vinyl(tributyl)stannane. Pd(PPh 3 ) 2 Cl 2 was also introduced more recently for Stille cross-couplings of, e.g., furane to purines by Persson et al 67 and to uridine by Tor et al 68 under reflux conditions in THF or dioxane. In our case, the reaction was carried out in DMF at room temperature yielding in 27% product 2 after 23 h and 45% 2 after 48 h (Table 2, exp.…”

Synthesis of Mimics to 5-(2″-thienyl)-2′,3′-β-Dideoxyuridine Triphosphate

“…The reduction of the bromoacetate with Zn/Cu in methanol (Starret et al, 1990) gave three components. From this crude mixture the 2',3'-didehy-~1~1 *Persson, et al, (1994).…”

“…The protected uridine analogue was iodinated in the 5-position with ceric ammonium nitrate (CAN) and iodine following the method used by Asakura and Robins, (1988). Pd(O)-catalysed cross-coupling reaction of 5' -Ovacetyl-z ,3'-dideoxy-5-iodo-uridine and 2-tributylstannylthiophene in an inert atmosphere (Persson et a/., 1994) yielded the protected 5' -O-acetyl-2',3' -dideoxy-5-(2" -thienyl) uridine in 58% yield. Removal of the acetyl group was achieved by standard hydrolysis using sodium methoxide in methanol.…”

“…In this paper the synthesis of some 5'-amido derivatives of 5-(2"-thienyl)-2',3',5'-~-trideoxyuridine is described ( Fig. 1) (Persson et al, 1994). In order to prevent possible cleavage of the 5'-a-ester nucleoside, the ester group was replaced with the more stable amido group.…”

“…The 2',3'-dideoxy analogue is active against HIV-RT, although less so than 2",3'-dideoxythymidine. These 5-(2"-thienyl) uridine analogues are inactive against HIV in cell-culture assays, most probably due to phosphorylation inefficiencies at some stage of the intracellular triphosphate synthesis (Persson et a/., 1994).…”