4'-SUBSTITUTED NUCLEOSIDES .5. HYDROXYMETHYLATION OF NUCLEOSIDE 5'-ALDEHYDES
4'-SUBSTITUTED NUCLEOSIDES .5. HYDROXYMETHYLATION OF NUCLEOSIDE 5'-ALDEHYDES
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DOI：
10.1021/jo01322a025
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发表时间：
1979-01-01
影响因子：
3.6
通讯作者：
MOFFATT, JG
中科院分区：
文献类型：
--
作者：
JONES, GH;TANIGUCHI, M;MOFFATT, JG
不同取代的5”-核苷醛和甲醛在水中氢氧化钠存在下发生交叉醛缩反应，经过限制性坎尼扎罗还原，生成相应的4”-羟甲基核苷衍生物。通过在初始醛产物中加入硼氢化物还原而不是依赖于正常的坎尼扎罗还原，上述反应的速度和总体效率得到了提高。与2',3' -未取代核苷5‘ -醛进行的这种反应在C3’得到4' -羟甲基核苷外聚物的混合物，可能是通过反向醛醇裂解然后再循环。对于这些反应，建议使用碱稳定的2',3' -O保护基团。在n6 -苯甲酰腺苷和n4 -苯甲酰胞苷5 -醛的2',3' - o -异丙基衍生物中，观察到丙酮被亚甲基交换，并提出了其机制。延伸到2''-脱氧核苷系列，相应的3''- o -苄基胸腺嘧啶5''-醛羟甲基化，然后催化氢解得到4''-（羟甲基）胸腺嘧啶。合成了一些新的，各种保护核苷5''-醛描述。
Crossed aldol condensations between variously substituted nucleoside 5''-aldehydes and formaldehyde in the presence of aqueous NaOH lead, following rate-limiting Cannizzaro reduction, to the corresponding 4''-hydroxymethyl nucleoside derivatives. The speed and overall efficiency of the above reactions are improved by incorporating a borohydride reduction of the initial aldol product rather than relying upon the normal Cannizzaro reduction. Such reactions conducted with 2'',3''-unsubstituted nucleoside 5''-aldehydes give mixtures of 4''-hydroxymethyl nucleosides epimeric at C3'' presumably via a reverse aldol cleavage followed by recyclization. The use of base stable 2'',3''-O protecting groups is recommended for these reactions. In the case of 2'',3''-O-isopropylidene derivatives of N6-benzoyladenosine and N4-benzoylcytidine 5''-aldehydes, some exchange of the acetonide by a methylene group is observed and a mechanism is proposed. For extension to the 2''-deoxynucleoside series, the corresponding hydroxymethylation of 3''-O-benzylthymidine 5''-aldehyde followed by catalytic hydrogenolysis leads to 4''-(hydroxymethyl)thymidine. Syntheses of a number of new, variously protected nucleoside 5''-aldehydes are described.