Regioselective solid-phase synthesis of nucleosides and carbohydrates triphosphates and triphosphotrithioates

ORGN 587

Yousef Ahmadibeni, and Keykavous Parang, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 41 Lower College Road, University of Rhode Island, Kingston, RI 02881
Nucleosides are activated to triphosphate forms in the presence of kinases. Nucleosides triphosphates are required for the synthesis of nucleotides and nucleic acids and the biological activity of nucleosides including several antiviral drugs. The regioselective synthesis of unprotected nucleosides and carbohydrate triphosphates is a challenging effort for organic chemists. Two classes of aminomethyl polystyrene resin-bound linkers of p-acetoxybenzyl alcohol were subjected to reactions with a triphosphitylating reagent containing bis(1,3-diisoproylphosphoramidite) in the presence of 1H-tetrazole to yield the corresponding polymer-bound triphosphitylating reagents. A number of unprotected carbohydrates (e.g., galactose, mannose, melibiose) and nucleosides (e.g., thymidine, uridine, adenosine, AZT) were reacted with the polymer-bound reagents. Oxidation with tert-butyl hydroperoxide or sulfurization with Beaucage's reagent, followed by removal of cyanoethoxy group with DBU, afforded the polymer-bound triphosphodiesters or triphosphotrithiodiesters. The acidic cleavage of polymer-bound compounds with TFA gave nucleosides and carbohydrates triphosphates and triphosphotrithioates with high regioselectivity in 39-74 % overall yield.


Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster

8:00 PM-10:00 PM, Monday, 29 August 2005 Washington DC Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005