Synthesis of Novel 3‘-<i>C</i>-Methylene Thymidine and 5-Methyluridine/Cytidine H-Phosphonates and Phosphonamidites for New Backbone Modification of Oligonucleotides
作者:Haoyun An、Tingmin Wang、Martin A. Maier、Muthiah Manoharan、Bruce S. Ross、P. Dan Cook
DOI:10.1021/jo001699u
日期:2001.4.1
ne)-protected H-phosphonate monomer 7. 5'-O-MMT-protected 3'-C-methylene-modified H-phosphonates 5, 3, and 7 were converted to the corresponding cyanoethyl H-phosphonates 50, 51, and 56 using DCC as a coupling reagent. One-pot three-step reactions of 50, 51, and 56 provided the desired 3'-C-methylene-modified phosphonamidite monomers 8-10. Some of these new 3'-methylene-modified monomers 1-10 have
新型5'-O-DMT-和MMT保护的3'-C-亚甲基修饰的胸苷,5-甲基尿苷和5-甲基胞苷H-膦酸酯1-7与O-甲基,氟,氢和O-(2通过一种新的有效策略,由相应的关键中间体3'-C-碘甲基核苷和中间体BTSP(通过Arbuzov反应原位制备)合成了2'-位的-甲氧基乙基)取代基。Arbuzov反应的修饰反应条件防止了DMT和MMT保护基的丢失,并直接提供了所需的5'-O-DMT-和/或MMT保护的3'-C-亚甲基修饰的H-膦酸酯1 -6虽然在PC键形成后也通过操纵保护基制备了一些。3'-C-碘甲基-5-甲基胞嘧啶53的修饰Arbuzov反应 由其5-甲基尿苷衍生物42制备,并用BTSP提供5-甲基胞嘧啶H-膦酸酯54,将其进一步转移到相应的4-N-(N-甲基吡咯烷-2-亚基)-保护的H-膦酸酯单体7。5使用DCC作为偶联剂,将'-O-MMT保护的3'-C-亚甲基改性的H-膦酸酯5、3和7