Synthesis of 1-[cis-3-(hydroxymethyl)cyclobutyl]-uracil, -thymine and -cytosine
Synthesis of 1-[cis-3-(hydroxymethyl)cyclobutyl]-uracil, -thymine and -cytosine
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DOI：
10.1039/a803878c
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发表时间：
1998-09-07
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影响因子：
--
通讯作者：
Song, QL
中科院分区：
文献类型：
--
作者：
Frieden, M;Giraud, M;Song, QL
以1-苯甲酰基尿嘧啶10a为起始原料，经三步反应制得4-（苄硫基）嘧啶-2（1H）-酮6a，总收率令人满意。通过烯丙基苄基醚与二氯烯酮的环加成反应，找到了可重复的反应条件，得到了高产率的环丁酮衍生物17。反式-3-（苄氧基甲基）环丁-1-醇15在标准Mitsunobu条件下与嘧啶衍生物6a在O-2上反应，得到化合物20，其以良好的总产率转化为2-[顺式-3-（羟甲基）环丁氧基]嘧啶-4（3 H）-酮24。在相同的Mitsunobu条件下，3-苯甲酰基尿嘧啶11 a和3-苯甲酰基胸腺嘧啶11b与N-1上的反式醇15反应，分别得到它们的1-[顺式-3-（苄氧基甲基）环丁基]衍生物27 a和27 b。后者化合物27 a和27 b以令人满意的总产率转化为1-[顺式-3-（羟甲基）环丁基]尿嘧啶13 a和1-[顺式-3-（羟甲基）环丁基]胸腺嘧啶13 b。尿嘧啶衍生物13 a以良好的产率转化为1-[顺式-3-（羟甲基）环丁基]胞嘧啶14。
4-(Benzylsulfanyl)pyrimidin-2(1H)-one 6a is prepared from 1-benzoyluracil 10a in three steps and in satisfactory overall yield. Reproducible conditions are found for the cycloaddition reaction between allyl benzyl ether and dichloroketene, leading to the cyclobutanone derivative 17 in good yield. trans-3-(Benzyloxymethyl)cyclobutan-1-ol 15 reacts under standard Mitsunobu conditions with the pyrimidine derivative 6a on O-2 to give compound 20, which is converted into 2-[cis-3-(hydroxymethyl)cyclobutoxy]pyrimidin-4(3H)-one 24 in good overall yield. Under the same Mitsunobu conditions, 3-benzoyluracil 11a and 3-benzoylthymine 11b react with the trans-alcohol 15 on N-1 to give their 1-[cis-3-(benzyloxymethyl)cyclobutyl] derivatives 27a and 27b, respectively. The latter compounds 27a and 27b are converted into 1-[cis-3-hydroxymethyl)cyclobutyl]uracil 13a and 1-[cis-3-(hydroxymethyl)cyclobutyl]thymine 13b in satisfactory overall yields. The uracil derivative 13a is converted into 1-[cis-3-(hydroxymethyl)cyclobutyl]cytosine 14 in good yield.