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Synthese und Eigenschaften von N 4 ‐Hexadecyl‐2′‐desoxycytidylyl‐(3′‐5′)‐5‐ethyl‐2′‐desoxyuridin und 2′‐Desoxythymidylyl‐(3′‐5′)‐ N 4 ‐hexadecyl‐1‐β‐ D ‐arabinofuranosylcytosin, zwei Vertreter einer neuen Prodrug‐Gruppe
Author(s) -
Schott Herbert,
Häussler Markus P.,
Schwendener Reto A.
Publication year - 1994
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199419940309
Subject(s) - chemistry , prodrug , nucleoside , phosphonate , amphiphile , liposome , chromatography , stereochemistry , organic chemistry , biochemistry , copolymer , polymer
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.