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Synthese und Eigenschaften vonN4-Hexadecyl-2′-desoxycytidylyl-(3′-5′)-5-ethyl-2′-desoxyuridin und 2′-Desoxythymidylyl-(3′-5′)-N4-hexadecyl-1-β-D-arabinofuranosylcytosin, zwei Vertreter einer neuen Prodrug-Gruppe

✍ Scribed by Schott, Herbert ;Häussler, Markus P. ;Schwendener, Reto A.


Publisher
John Wiley and Sons
Year
1994
Tongue
English
Weight
625 KB
Volume
1994
Category
Article
ISSN
0947-3440

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✦ Synopsis


Synthesis and Properties of N^4^‐Hexadecyl‐2′‐deoxycytidylyl‐(3′‐5′)‐5‐ethyl‐2′‐deoxyuridine and 2′‐Deoxythymidylyl‐(3′‐5′)‐N^4^‐hexadecyl‐1‐β‐D‐arabinofuranosylcytosine, Two 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 antineoplastic N^4^‐hexadecyl‐1‐β‐D‐arabinofuranosylcytosine via a 3′‐5′‐phosphodiester linkage using the hydrogen phosphonate method is described. The purity and the structure of the synthetic products were determined 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 hydrophilic nucleoside residues are applied for the masking of 5′‐phosphorylated nucleoside analogues which are known as chemotherapeutics. The prodrugs are soluble in water and can also be incorporated together with matrix lipids into stable liposome dispersions. magnified image