Efficient one-step Suzuki arylation of unprotected halonucleosides, using water-soluble palladium catalysts
Efficient one-step Suzuki arylation of unprotected halonucleosides, using water-soluble palladium catalysts
复制标题
DOI：
10.1021/jo034289p
复制
发表时间：
2003-08-22
影响因子：
3.6
通讯作者：
Shaughnessy, KH
中科院分区：
文献类型：
--
作者：
Western, EC;Daft, JR;Shaughnessy, KH
核苷的修饰以获得具有药物活性的化合物，诱变模型和寡核苷酸结构探针仍然是人们非常感兴趣的。本文报道了无保护卤核苷的水相修饰。以三（3-磺基苯基）膦（TPPTS）和醋酸钯为催化剂，8-溴-2′-脱氧鸟苷（8-BrdG）与芳基硼酸偶联得到8-芳基-2′-脱氧鸟苷加合物（8-ArdG），在2:1的水：乙腈溶剂混合物中收率很高。在这种偶联反应中，发现TPPTS配体优于水溶性烷基膦。偶联化学已扩展到8-溴2'-脱氧腺苷（8-BrdA）和5-碘-2'-脱氧尿苷（5-IdU），以及8-溴鸟苷和8-溴腺苷的核糖核苷。在所有情况下，芳基化加合物的收率都很好。使用三（4,6-二甲基-3-磺酰基）膦（TXPTS）， 8-BrdA和5-IdU的铃木偶联可以在室温下不到1小时完成。这种方法代表了一种有效和通用的卤核苷芳化方法，不需要事先保护核苷。
Modification of nucleosides to give pharmaceutically active compounds, mutagenesis models, and oligonucleotide structural probes continues to be of great interest. The aqueous-phase modification of unprotected halonucleosides is reported herein. Using a catalyst derived from tris(3-sulfonatophenyl)phosphine (TPPTS) and palladium acetate, 8-bromo-2'-deoxyguanosine (8-BrdG) is coupled with arylboronic acids to give 8-aryl-2'-deoxyguanosine adducts (8-ArdG) in excellent yield in a 2:1 water: acetonitrile solvent mixture. The TPPTS ligand was found to be superior to water-soluble alkylphosphines for this coupling reaction. The coupling chemistry has been extended to 8-bromo2'-deoxyadenosine (8-BrdA) and 5-iodo-2'-deoxyuridine (5-IdU), as well as the ribonucleosides 8-bromoguanosine and 8-bromoadenosine. Good to excellent yields of arylated adducts are obtained in all cases. With use of tri(4,6-dimethyl-3-sulfonatophenyl)phosphine (TXPTS), the Suzuki coupling of 8-BrdA and 5-IdU can be accomplished in less than 1 h at room temperature. This methodology represents an efficient and general method for halonucleoside arylation that does not require prior protection of the nucleoside.