Colman-Saizarbitoria T, Gu Z M, Zhao G X, Zeng L, Kozlowski J F, McLaughlin J L
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacacol Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
J Nat Prod. 1995 Apr;58(4):532-9. doi: 10.1021/np50118a008.
Asimicin and a new cytotoxic Annonaceous acetogenin, venezenin [1], were isolated from the bark of Xylopia aromatica by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings and possessing a double bond located two methylenes away from a vicinal diol in the hydrocarbon chain. The structure of 1 was elucidated by 1H- and 13C-nmr, COSY, single-relayed COSY, and by HMBC techniques, and derivatization. Annomontacin 10-one [6] and 18/21-cis-annomontacin-10-one [7], two semi-synthetic mono-THF acetogenins were prepared from 1. These acetogenins showed cytotoxicity, comparable or superior to adriamycin, against three human solid tumor cell lines. Reduction of the 10-keto of 1 to the racemic OH-10 derivative enhanced the bioactivity, as did the conversion of 1 to 6 and 7. Venezenin [1], like other Annonaceous acetogenins, showed inhibition of oxygen uptake by rat liver mitochondria and demonstrated that the THF ring may not be essential to this mode of action.
通过利用卤虫致死率进行生物活性导向分级分离，从芳香肉豆蔻的树皮中分离出了番荔枝辛和一种新的具有细胞毒性的番荔枝产乙酸素——venezenin [1]。化合物1代表一种不寻常类型的C37番荔枝产乙酸素，既没有四氢呋喃（THF）环也没有环氧环，并且在烃链中离邻二醇两个亚甲基的位置有一个双键。通过1H-和13C-核磁共振、COSY、单中继COSY以及HMBC技术和衍生化确定了1的结构。由1制备了两种半合成的单THF产乙酸素——番荔枝蒙他星10-酮[6]和18/21-顺式-番荔枝蒙他星-10-酮[7]。这些产乙酸素对三种人类实体瘤细胞系显示出与阿霉素相当或优于阿霉素的细胞毒性。将1的10-酮还原为外消旋OH-10衍生物增强了生物活性，将1转化为6和7时也是如此。Venezenin [1]与其他番荔枝产乙酸素一样，显示出对大鼠肝线粒体氧摄取的抑制作用，并表明THF环对于这种作用方式可能不是必需的。
