SYNTHESIS AND PROPERTIES OF N-4-HEXADECYL -2'-DEOXYCYTIDYL-(3'-5')-5-ETHYL-2'-DEOXYURIDINE AND )-N-4-HEXADECYL-1-BETA-D-ARABINOFURANOSYLCYTOSINE, 2 REPRESENTATIVES OF A NEW KIND OF PRODRUGS

The gram-scale condensation of N-4-hexadecyl-2'-deoxycytidine with the antiviral 5-ethyl-2'-deoxyuridine and of 2'-deoxythymidine with the a ntineoplastic N-4-hexadecyl-1-beta-D-arabinofuranosylcytosine via a 3' -5'-phosphodiester linkage using the hydrogen phosphonate method is de scribed. The purity and the structure of the synthetic products were d etermined chromatographically (TLC, HPLC) and spectroscopically (MS-MS , 2D-NMR). The resulting amphiphilic dinucleoside phosphates represent two examples of a new kind of prodrugs in which lipophilic or hydroph ilic nucleoside residues are applied for the masking of 5'-phosphoryla ted nucleoside analogues which are known as chemotherapeutics. The pro drugs are soluble in water and can also be incorporated together with matrix lipids into stable liposome dispersions.