Li N S, Tang X Q, Piccirilli J A
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, The University of Chicago, 5841 S. Maryland Avenue, MC 1028, Chicago, Illinois 60637, USA.
Org Lett. 2001 Apr 5;3(7):1025-8. doi: 10.1021/ol0155687.
[structure: see text]. The first synthesis of 2'-C-beta-trifluoromethyl pyrimidine ribonucleosides is described. 1,2,3,5-Tetra-O-benzoyl-2-C-beta-trifluoromethyl-alpha-D-ribofuranose (3) is prepared from 1,3,5-tri-O-benzoyl-alpha-D-ribofuranose (1) in three steps and converted to 3,5-di-O-benzoyl-2-C-beta-trifluoromethyl-alpha-D-1-ribofuranosyl bromide (5). The 1-bromo derivative (5) is found to be a powerful reaction intermediate for the synthesis of ribonucleosides. The reaction of silylated pyrimidines with (5) in the presence of HgO/HgBr2 affords exclusively the beta-anomers (6-8). Deprotection of (6-8) with ammonia in methanol yields the 2'-C-beta-trifluoromethyl nucleosides (9-11).
[结构：见正文]。描述了2'-C-β-三氟甲基嘧啶核糖核苷的首次合成。1,2,3,5-四-O-苯甲酰基-2-C-β-三氟甲基-α-D-呋喃核糖（3）由1,3,5-三-O-苯甲酰基-α-D-呋喃核糖（1）分三步制备，并转化为3,5-二-O-苯甲酰基-2-C-β-三氟甲基-α-D-1-呋喃核糖基溴（5）。发现1-溴衍生物（5）是合成核糖核苷的有力反应中间体。在HgO/HgBr2存在下，硅烷化嘧啶与（5）反应仅生成β-异头物（6-8）。在甲醇中用氨对（6-8）进行脱保护得到2'-C-β-三氟甲基核苷（9-11）。
