RIKEN ASI, Wako-shi, Saitama 351-0198, Japan.
Bioorg Med Chem Lett. 2012 Jul 1;22(13):4259-62. doi: 10.1016/j.bmcl.2012.05.022. Epub 2012 May 15.
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 (±)-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 (±)-1 had no such activity.
通过全合成确定了诺拉烷萜烯的完整结构，库加伯醇（1）。全合成的关键特点是：（1）通过苯甲酰胺的 o-锂化反应引入异戊基；（2）通过 RCM 反应构建四氢萘酮；（3）通过相应的樟脑酸盐的色谱分离对（±）-1 进行光学拆分。从极性较大的樟脑酸盐中获得的对溴苯甲酸酯的 X 射线晶体学分析表明，天然库加伯醇具有 S 构型。天然对映体及其（R）对映异构体对突变酵母和 HL-60 细胞均表现出相同的抑制活性，而（±）-1 中 C-8 和 9 位没有烷基的简单类似物则没有这种活性。
