Boesen Thomas, Madsen Christian, Pedersen Daniel Sejer, Nielsen Brian M, Petersen Asger B, Petersen Michael A, Munck Michael, Henriksen Ulla, Nielsen Claus, Dahl Otto
Department of Chemistry, University of Copenhagen, The H. C. Ørsted Institute, Universitetsparken 5, DK-2100 Copenhagen, Denmark.
Org Biomol Chem. 2004 Apr 21;2(8):1245-54. doi: 10.1039/b316304k. Epub 2004 Mar 16.
Acyclic, achiral nucleoside derivatives 1b-e of adenine, cytosine, 5-methylcytosine, and guanine, containing a 3-hydroxy-2-(hydroxymethyl)prop-1-enyl group on N-1 or N-9, have been prepared analogously to the previously described thymine derivative 1a. In contrast to the adenine and guanine derivatives, the cytosine derivative 9 was unstable, and was obtained in a low yield due to side reactions. These include cleavage of the propenyl group from the base, and the formation of a bicyclic compound. The thymine derivative, although stable under neutral conditions, likewise underwent a reversible cyclization reaction (Michael addition) in the presence of acids or bases. The 5-methylcytosine derivative was stable under neutral and basic conditions. Four other nucleoside derivatives 26a-d containing a 2,3-dihydroxy-2-(hydroxymethyl)propyl group on N-1 or N-9, three of which are new, have likewise been prepared. All compounds were evaluated as antiviral agents against HIV-1 and HSV-1 but were devoid of antiviral activity.
已按照与先前描述的胸腺嘧啶衍生物1a类似的方法制备了腺嘌呤、胞嘧啶、5-甲基胞嘧啶和鸟嘌呤的无环、非手性核苷衍生物1b - e，其在N - 1或N - 9上含有一个3 - 羟基 - 2 - (羟甲基)丙 - 1 - 烯基。与腺嘌呤和鸟嘌呤衍生物不同，胞嘧啶衍生物9不稳定，由于副反应产率较低。这些副反应包括丙烯基从碱基上断裂以及双环化合物的形成。胸腺嘧啶衍生物虽然在中性条件下稳定，但在酸或碱存在下同样会发生可逆的环化反应（迈克尔加成）。5 - 甲基胞嘧啶衍生物在中性和碱性条件下稳定。同样制备了另外四种核苷衍生物26a - d，其在N - 1或N - 9上含有一个2,3 - 二羟基 - 2 - (羟甲基)丙基，其中三种是新的。所有化合物均作为抗HIV - 1和HSV - 1的抗病毒剂进行了评估，但均无抗病毒活性。
