化学
氨基
迈克尔反应
生物碱
有机催化
催化作用
有机化学
组合化学
对映选择合成
作者
Kyosuke Yamanishi,Gin Ashihara,Shinya Shiomi,Shingo Harada,Mariko Kitajima,Hiromitsu Takayama,Mariko Kitajima
摘要
Natural products have historically been actively evaluated for their biological activity in the development of pharmaceuticals, while their evaluation as asymmetric catalysts has rarely been explored. In this study, we evaluated the catalytic activity of the natural product library. Three naturally occurring alkaloids, gardnerine, spiradine A, and calycanthine, were found to catalyze an asymmetric Michael reaction using oxindole and nitrostyrene. We further studied (+)-calycanthine, which is characterized by its aminal structure. Concise synthetic and extraction protocols were developed to provide both enantiomers of calycanthine. Further derivatization of this alkaloid led to improved enantioselectivity in a model reaction. Computational studies suggested that the aminal moiety of the catalyst activated nucleophiles and electrophiles through multiple hydrogen bonding interactions, including nonclassical hydrogen bonds between carboxylic acid and the aminal C-H.
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