NUCLEIC-ACID RELATED-COMPOUNDS .39. EFFICIENT CONVERSION OF 5-IODO TO 5-ALKYNYL AND DERIVED 5-SUBSTITUTED URACIL BASES AND NUCLEOSIDES
NUCLEIC-ACID RELATED-COMPOUNDS .39. EFFICIENT CONVERSION OF 5-IODO TO 5-ALKYNYL AND DERIVED 5-SUBSTITUTED URACIL BASES AND NUCLEOSIDES
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DOI：
10.1021/jo00159a012
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发表时间：
1983-01-01
影响因子：
3.6
通讯作者：
BARR, PJ
中科院分区：
文献类型：
--
作者：
ROBINS, MJ;BARR, PJ
在二（三苯基膦）氯化钯（II）和碘化铜（I）存在下，在温的三乙胺中，以高产率进行末端炔与5-碘-1-甲基尿嘧啶和5-碘尿嘧啶核苷（作为其对甲苯甲酰基酯保护）的偶联。几个随后脱保护的5-炔基-2“-脱氧尿苷，包括母体5-乙炔基-2”-脱氧尿苷，具有抗病毒活性;它们的5“-单磷酸抑制胸苷酸合成酶。控制5-炔基侧链的氢化，得到（Z）-5-烯基-或饱和的5-烷基-2“-脱氧尿苷。这提供了已知的5-乙基-和5-正己基-2“-脱氧尿苷和（E）-5-（2-溴乙烯基）-2”-脱氧尿苷的立体控制路线。在有利的情况下，三键的水合得到相应的尿嘧啶-5-烷酮产物。
Coupling of terminal alkynes with 5-iodo-1-methyluracil and 5-iodouracil nucleosides (protected as their p-toluyl esters) proceeded in high yields in the presence of bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide in warm triethylamine. Several of the subsequently deprotected 5-alkynyl-2''-deoxyuridines, including the parent 5-ethynyl-2''-deoxyuridine, had antiviral activity; their 5''-monophosphates inhibited thymidylate synthetase. Hydrogenation of the 5-alkynyl side chain was controlled to give (Z)-5-alkenyl- or the saturated 5-alkyl-2''-deoxyuridines. This provided a stereocontrolled route to the known 5-ethyl- and 5-n-hexyl-2''-deoxyuridines and (E)-5-(2-bromovinyl)-2''-deoxyuridine. Hydration of the triple bond gave corresponding uracil-5-alkanone products in favorable cases.