ORGN 217 |
| Nucleosides are intracellularly converted to nucleoside triphosphates in the presence of kinases. The synthesis and biological properties of nucleosides β-triphosphates have not been reported, possibly due to the challenges in their synthesis. A solid-phase method was developed for β-triphosphorylation of unprotected nucleosides. First, the synthesis of a β-triphosphitylating reagent was accomplished in 91% yield using phosphorus trichloride, 3-hydroxypropionitrile, and diisopropylamine as starting materials. Aminomethyl polystyrene resin-bound linker of p-acetoxybenzyl alcohol was subjected to reaction with the β-triphosphitylating reagent to yield the corresponding polymer-bound β-triphosphitylating reagent (1). The solid-phase reagent (1) was reacted with unprotected nucleosides (e.g., AZT, cytidine, thymidine, uridine, inosine, adenosine) in the presence of 1H-tetrazole to afford 2. Polymer-bound nucleosides underwent oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford 5'-O-β-triphosphorylated nucleosides (3a-f, 63-87% isolated yields) with high regioselectivity.
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Asymmetric Reactions and Syntheses, Metal-Mediated Reactions, Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 PM-10:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Organic Chemistry |
