Synthesis of a TNF inhibitor, flurbiprofen and an i-Pr analogue in enantioenriSynthesis of a TNF inhibitor, flurbiprofen and an i-Pr analogue in enantioenriched forms by copper catalyzed propargylic substitution with Grignard reagents
Synthesis of a TNF inhibitor, flurbiprofen and an i-Pr analogue in enantioenriSynthesis of a TNF inhibitor, flurbiprofen and an i-Pr analogue in enantioenriched forms by copper catalyzed propargylic substitution with Grignard reagents
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TNF 抑制剂、氟比洛芬和 i-Pr 类似物的对映体合成通过铜催化用格氏试剂进行炔丙取代，合成对映体富集形式的 TNF 抑制剂、氟比洛芬和 i-Pr 类似物
DOI：
10.1039/d1ob01944a
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
and Y. Kobayashi
中科院分区：
文献类型：
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作者：
Yuji Y. Takashima;Y. Isogawa;A. Tsuboi;N. Ogawa;and Y. Kobayashi
由TMSCCCH（OH）CH_2CH_2 OTBDPS衍生的磷酸二乙酯在铜催化下与3-c-C_5 H_9 -4-MeOC_6 H_3 MgBr发生取代反应，经多次转化，得到一种含Ph-乙炔基的肿瘤坏死因子抑制剂。以苯乙炔磷酸酯PhCCCH（OP（O）（OEt）2）CH 2CH 2 OTBDPS为原料合成了缓蚀剂。此外，TMSCCCH（OH）CH 3和TMSCCCH（OH）-i-Pr衍生的磷酸酯分别被3-F-4-PhC 6 H3 MgBr取代，得到相应的取代产物，并分别转化为氟比洛芬及其i-Pr类似物。在这些合成中的铜催化的取代进行区域和立体选择性的方式。
The copper-catalyzed substitution reaction of diethyl phosphate derived from TMSCCCH(OH)CH2CH2OTBDPS with 3-c-C5H9-4-MeOC6H3MgBr, 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)2)CH2CH2OTBDPS. Furthermore, the substitution of phosphates derived from TMSCCCH(OH)CH3 and TMSCCCH(OH)-i-Pr with 3-F-4-PhC6H3MgBr gave the corresponding substitution products, which were transformed to flurbiprofen and its i-Pr analogue, respectively. The copper-catalyzed substitutions in these syntheses proceeded in a regio- and stereoselective manner.