Density Functional Theory Calculations in Stereochemical Determination of Terpecurcumins J鈥揥, Cytotoxic Terpene-Conjugated Curcuminoids from Curcuma longa L.

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• 作者：Xionghao Lin ; Shuai Ji ; Xue Qiao ; Hongbo Hu ; Ni Chen ; Yinhui Dong ; Yun Huang ; Dean Guo ; Pengfei Tu ; Min Ye
• 刊名：Journal of Organic Chemistry
• 出版年：2013
• 出版时间：December 6, 2013
• 年：2013
• 卷：78
• 期：23
• 页码：11835-11848
• 全文大小：660K
• 年卷期：v.78,no.23(December 6, 2013)
• ISSN：1520-6904

文摘

Fourteen novel terpene-conjugated curcuminoids, terpecurcumins J鈥揥 (1鈥?b>14), have been isolated from the rhizomes of Curcuma longa L. Among them, terpecurcumins J鈥換 and V represent four unprecedented skeletons featuring an unusual core of hydrobenzannulated[6,6]-spiroketal (1 and 2), bicyclo[2.2.2]octene (3鈥?b>7), bicyclo[3.1.3]octene (8), and spiroepoxide (13), respectively. The structures of compounds 1鈥?b>14 were elucidated by extensive spectroscopic analysis, and their absolute configurations were established by electronic circular dichroism, vibrational circular dichroism, and ¹³C NMR spectroscopic data analysis, together with density functional theory calculations. The structure and configuration of 1 was further confirmed by single-crystal X-ray diffraction (Cu K伪). The biogenetic pathways of 1鈥?b>14 were proposed, involving Michael addition, condensation, Diels鈥揂lder cycloaddition, and electrophilic substitution reactions. Terpecurcumins showed more potent cytotoxic activities than curcumin and ar-/尾-turmerone. Among them, terpecurcumin Q (8) exhibited IC₅₀ of 3.9 渭M against MCF-7 human breast cancer cells, and mitochondria-mediated apoptosis played an important role in the overall growth inhibition. Finally, LC/MS/MS quantitative analysis of five representative terpecurcumins indicated these novel compounds were present in C. longa at parts per million level.