Preparation of Purine 2'-Deoxy-5'-O-phosphonomethylnucleosides and 2'-Deoxy-3'-O-phosphonomethylnucleosides

Abstract

Sodium salt of 2'-deoxy-N6-dimethylaminomethylene-3'-O-(tetrahydro-2H-pyran-2-yl)adenosine (VIII) reacted with dibenzyl p-toluenesulfonyloxymethanephosphonate (Ia) to give dibenzyl ester of 2'-deoxy-N6-dimethylaminomethylene-5'-O-phosphonomethyl-3'-O-(tetrahydro-2H-pyran-2-yl)adenosine (XI) which after deprotection afforded the final 2'-deoxy-5'-O-phosphonomethyladenosine (XII). 2'-Deoxy-5'-O-hydroxymethanephosphonyladenosine (XIV) and 5'-O-benzyloxymethanephosphonyl-2'-deoxyadenosine (XIII) were isolated as a side product. The preparation of 2'-deoxy-5'-O-phosphonomethylguanosine (XVI) and protection of the starting nucleoside were analogous to those of compound XII. In the 2'-deoxy-3'-O-phosphonomethylnucleosides series, 2'-deoxy-3'-O-phosphonomethylcytidine (XXI) and 2'-deoxy-3'-O-phosphonomethyladenosine (XXVII) were prepared, using N4-benzoyl-5'-O-tert-butyldiphenylsilyl-2'-deoxycytidine (XVIII) and 5'-O-tert-butyldiphenylsilyl-2'-deoxy-N6-dimethylaminomethyleneadenosine (XXIV), respectively, as starting compounds.