Department of Biomolecular Engineering, Tokyo Institute of Technology, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan.
Department of Applied Chemistry, Meiji University, 1-1-1, Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan.
Org Biomol Chem. 2021 Nov 25;19(45):9906-9909. doi: 10.1039/d1ob01944a.
The copper-catalyzed substitution reaction of diethyl phosphate derived from TMSCCCH(OH)CHCHOTBDPS with 3--CH-4-MeOCHMgBr, followed by several transformations, afforded a tumor necrosis factor inhibitor possessing a Ph-acetylene moiety. The inhibitor was also synthesized from phenylacetylene phosphate PhCCCH(OP(O)(OEt))CHCHOTBDPS. Furthermore, the substitution of phosphates derived from TMSCCCH(OH)CH and TMSCCCH(OH)--Pr with 3-F-4-PhCHMgBr gave the corresponding substitution products, which were transformed to flurbiprofen and its -Pr analogue, respectively. The copper-catalyzed substitutions in these syntheses proceeded in a regio- and stereoselective manner.
三甲基硅基乙炔基甲醇磷酸酯与 3--CH-4-MeOCHMgBr 的铜催化取代反应，随后经过几步转化，得到了一个具有 Ph-乙炔部分的肿瘤坏死因子抑制剂。该抑制剂也可以由苯乙炔磷酸酯 PhCCCH(OP(O)(OEt))CHCHOTBDPS 合成。此外，三甲基硅基乙炔基甲醇和三甲基硅基乙炔基丙醇磷酸酯与 3-F-4-PhCHMgBr 的取代反应得到了相应的取代产物，分别转化为氟比洛芬及其丙基类似物。这些合成中的铜催化取代反应以区域和立体选择性的方式进行。
