Synthesis of 5-fluoroalkylated pyrimidine nucleosides via Negishi cross-coupling
Synthesis of 5-fluoroalkylated pyrimidine nucleosides via Negishi cross-coupling
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DOI：
10.1021/jo800444y
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发表时间：
2008-07-04
影响因子：
3.6
通讯作者：
Kung, Hank F.
中科院分区：
文献类型：
--
作者：
Chacko, Ann-Marie;Qu, Wenchao;Kung, Hank F.
5-氟烷基化嘧啶核苷（1）具有作为靶向HSV 1-tk自杀基因治疗的治疗剂和分子成像剂的潜力。因此，已经开发了5-氟烷基化核苷衍生物的直接制备。本文报道了Pd催化的Negishi交叉偶联3-N-苯甲酰基-3 '，5'-二-O-苯甲酰基-5-碘-2 '-脱氧尿苷（2a）和3-N-苯甲酰基-3'，5 '-二-O-苯甲酰基-5-碘-2'-脱氧-2 '-氟阿拉伯尿苷（2b）与未活化的CSp（3）氟烷基溴化锌的第一个实例。本文首次合成了6个具有3 - 5个亚甲基链长的5-氟烷基-2 '-脱氧嘧啶核苷衍生物（5）。此外，这种方法已被扩展到创建一系列的13个5-烷基取代的核苷，包括目标核苷5和5-甲硅烷基氧基丙基和5-氰基丁基衍生物。
5-Fluoroalkylated pyrimidine nucleosides (1) have potential as therapeutic agents and molecular imaging agents targeting HSV1-tk suicide gene therapy. Thus, straightforward preparation of 5-fluoroalkylated nucleoside derivatives has been developed. Reported herein are the first examples of Pd-catalyzed Negishi cross-coupling of 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine (2a) and 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxy-2'-fluoroarabinouridine (2b) with unactivated CSp(3) fluoroalkylzinc bromides. This paper demonstrates the first synthesis of six 5-fluoroalkyl-2'-deoxypyrimidine nucleoside derivatives with three to five methylene chain lengths (5). Furthermore, this methodology has been extended to create a series of 13 5-alkyl-substituted nucleosides, including the target nucleosides 5 and 5-silyloxypropyl and 5-cyanobutyl derivatives.