Synthesis and biological activity of both enantiomers of kujigamberol isolated from 85-million-years-old Kuji amber

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• 作者：Yue Qi Ye^a ; Hiroyuki Koshino^a ; Daisuke Hashizume^a ; Yuki Minamikawa^b ; Ken-ichi Kimura^b ; Shunya Takahashi^a ; ^{shunyat@riken.jp}
• 关键词：Kuji amber ; Kujigamberol ; Norlabdane terpenoid ; RCM reaction ; Inhibitory activity toward HL-60 cells
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 July, 2012
• 卷：22
• 期：13
• 页码：4259-4262
• 文件大小：451 K

摘要

The full-structure of a norlabdane terpenoid, kujigamberol (1) was determined by total synthesis. Key features of the total synthesis are (1) installation of isopentyl group through an o-lithiation of benzamide, (2) construction of tetralone by the RCM reaction, and (3) optical resolution of (卤)-1 using chromatographical separation of the corresponding camphanates. X-ray crystallographical analysis of p-bromobenzoate obtained from the more polar camphanate that was identical with a natural derivative, revealed natural kujigamberol to have an S-configuration. Both the natural enantiomer and its (R)-antipode showed the same inhibitory activity toward the mutant yeast and HL-60 cells, while simple analogs without alkyl groups at the C-8 and 9 positions of (卤)-1 had no such activity