ORGN 639 |
| Modified nucleoside triphosphates have received much attention in the study of numerous biochemical and pharmacological processes. Nucleoside triphosphate derivatives containing a, b- or b, g-methylene groups are commonly used in nucleic acid research since they are resistant to hydrolysis by enzymatic dephosphorylation. The solution-phase synthesis of these compounds is challenging, because of the requirements for the synthesis and purification of intermediates, protection and deprotection steps, and low yields. Bis(dichlorophosphino)methane was converted to a, b- or b, g-methylene-triphosphitylating reagents with reactions with 3-hydroxypropionitrile, diisopropylamine, and water. The reagents were reacted with aminomethyl polystyrene resin-bound linker of 4-acetoxy-3-phenylbenzyl alcohol to afford the corresponding polymer-bound a, b- or b, g-methylene-triphosphitylating reagents. The solid-phase reagents were reacted with unprotected nucleosides (e.g., thymidine, adenosine) 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 yield 5'-O-a, b- and b, g-methylene nucleoside triphosphates in 53-84% isolated yields and high selectivity.
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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 |
