Synthesis of acyclic nucleotide analogues derived from N3-substituted isoguanine

被引：0
|
作者：
Alexander, P [1 ]
Holy, A [1 ]
Budesínsky, M [1 ]
Masojídková, M [1 ]
机构：
[1] Acad Sci Czech Republ, Inst Organ Chem & Biochem, CR-16610 Prague 6, Czech Republic
来源：
COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS | 2000年 / 65卷 / 11期
关键词：
purines; nucleosides; nucleotides; acyclic analogs; phosphonates; alkylation; antivirals;
D O I：
10.1135/cccc20001713
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Reaction of 9-benzyl-6-{[(dimethylamino)methylidene]amino}purin-2(3H)-one (7) with ethylene carbonate gave a mixture of 9-benzyl-2-(2-hydroxyethoxy)purin-6-amine (10) and 2-amino-9-benzyl-3-(2-hydroxyethyl)purin-2(3H)-one (11). This mixture reacted with diisopropyl (tosyloxymethyl)phosphonate in the presence of NaH followed by catalytic hy drogenation and bromotrimethylsilane treatment to afford isomeric 6-amino-3-[2-(phosphonomethoxy)ethyl]purin-2(3H)-one (3) and 2-[2-(phosphonomethoxy)ethoxy]purin-6-amine (15). Similar treatment of compound 7 with tritylglycidol gave two isomeric 2-hydroxy-3-(trityloxy)propyl derivatives 18, 20 which were subsequently condensed with diisopropyl (tosyloxymethyl)phosphonate to afford protected diester intermediates 21 and 22; these compounds were transformed by hydrogenolysis and ester cleavage with bromotrimethlylsilane to the isomeric 6-amino-3-[3-hydroxy-2-(phosphonomethoxy)propyl]-purin-2(3H)-one (2) and 2-[3-hydroxy-2-(phosphonomethoxy)propoxy]purin-6-amine (24). None of the free phosphonates 2, 3, 15 or 24 exhibited any antiviral or cytostatic activity.
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页码：1713 / 1725
页数：13
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