- 作者: 程正禹 ; 劉邦一 ; 紀孝慈
- 作者服務機構: 台灣大學藥學系
- 中文摘要: Diethylaluminum trimethylsilylacetylide reacted stereospecifically with the mesylate of trans-2-(N- pyrrolidinyl)cyclohexanol to give trans-N- [ 2-(trimethylsilylacetylenyl)cyclohexyl ] pyrrolidine (3). The trimethylsilyl group in 3 was displaced with a 3,4- dichlorobenzoyl group to give ynone, which then underwent 1, 4-addition with lithium dimethylcuprate to give trans enone and its cis isomer in a ratio 5:1. Reduction of the enones with NaBH/sub 4//CeCl/sub 3/ resulted in cis and trans allylic alcohols 9 and 10. Both 9 and 10 were successfully deoxygenated with Znl/sub 2/-NaCNBH/sub 3/ reducing system to give trans-(E)-N- { 2- [ 4-(3,4-dichlorophenyl)but-2- en-2-yl ] cyclohexyl } pyrrolidine (11) as the only product. Olefin 11, a carbon-carbon double bond isostere of the prototype .kappa.-selective opioid analgesic U-50488, showed a 10/sup 3/ fold reduction in .kappa.-affinity(K/sub i,.kappa./=1.6*10/sup 4/nM vs. 15nM for U-50488).
- 英文摘要: --
- 中文關鍵字: Organoaluminum Acetylide; Alkene; Kappa Opioid; Stereospecificity; Stereoselectivity; Pyrrolidine
- 英文關鍵字: 有機鋁炔類化合物;烯屬烴;卡巴鴉片;立體特異性;立體選擇性;喀啶