ORGN 641 |
| Modified nucleoside triphosphates are urgently needed to investigate the roles of phosphate transfer in biological systems and to elucidate the mechanism of the enzymatic reactions that use natural nucleoside triphosphates as substrates. As part of our ongoing investigation to synthesize modified triphosphate analogues, nucleoside 5'-O-b-triphosphates containing a-b-methylene bridge were synthesized. First, a, b-methylene b-triphosphitylating reagent was synthesized by the reaction of bis(dichlorophosphino)methane with 3-hydroxypropionitrile,diisopropylamine, and water. Then aminomethyl polystyrene resin-bound linker of 4-acetoxy-3-phenylbenzyl alcohol was subjected to reaction with the b-triphosphitylating reagent to yield the corresponding polymer-bound b-triphosphitylating reagent. Finally, the solid-phase reagent was reacted with unprotected nucleosides (e.g., adenosine, 3¢-azido-3¢-deoxythymidine, 3¢-fluoro-3¢-deoxythymidine, 2',3'-didehydro-2',3'-dideoxythymidine, cytidine, inosine) in the presence of 5-(ethylthio)-1H-tetrazole, followed by oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford nucleoside 5'-O-a,b-methylene-b-triphosphates in 47-73% isolated yields and high selectivity.
|
|
Asymmetric Reactions, Combinatorial Chemistry, Molecular Recognition and Self-Assembly, Proteins, Peptides, Amino Acids and Enzyme Inhibitors
8:00 PM-10:00 PM, Wednesday, March 28, 2007 Hyatt Regency Chicago -- Riverside Center, Poster
Division of Organic Chemistry |
