Kutrzeba Lukasz, Dayan Franck E, Howell J'Lynn, Feng Ju, Giner José-Luis, Zjawiony Jordan K
Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.
Phytochemistry. 2007 Jul;68(14):1872-81. doi: 10.1016/j.phytochem.2007.04.034. Epub 2007 Jun 14.
Salvinorin A, a neoclerodane diterpenoid, isolated from the Mexican hallucinogenic plant Salvia divinorum, is a potent kappa-opioid receptor agonist. Its biosynthetic route was studied by NMR and HR-ESI-MS analysis of the products of the incorporation of [1-(13)C]-glucose, [Me-(13)C]-methionine, and [1-(13)C;3,4-(2)H2]-1-deoxy-D-xylulose into its structure. While the use of cuttings and direct-stem injection were unsuccessful, incorporation of (13)C into salvinorin A was achieved using in vitro sterile culture of microshoots. NMR spectroscopic analysis of salvinorin A (2.7 mg) isolated from 200 microshoots grown in the presence of [1-(13)C]-glucose established that this pharmacologically important diterpene is biosynthesized via the 1-deoxy-D-xylulose-5-phosphate pathway, instead of the classic mevalonic acid pathway. This was confirmed further in plants grown in the presence of [1-(13)C;3,4-(2)H2]-1-deoxy-D-xylulose. In addition, analysis of salvinorin A produced by plants grown in the presence of [Me-(13)C]-methionine indicates that methylation of the C-4 carboxyl group is catalyzed by a type III S-adenosyl-L-methionine-dependent O-methyltransferase.
从墨西哥致幻植物鼠尾草中分离出的新克罗烷二萜类化合物萨尔维诺林A是一种强效κ-阿片受体激动剂。通过对[1-(13)C]-葡萄糖、[Me-(13)C]-甲硫氨酸和[1-(13)C;3,4-(2)H2]-1-脱氧-D-木酮糖掺入其结构的产物进行核磁共振（NMR）和高分辨电喷雾电离质谱（HR-ESI-MS）分析，研究了其生物合成途径。虽然使用插条和直接茎注射未成功，但通过微芽的体外无菌培养实现了(13)C掺入萨尔维诺林A。对在[1-(13)C]-葡萄糖存在下生长的200个微芽中分离出的2.7毫克萨尔维诺林A进行核磁共振光谱分析，确定这种具有重要药理作用的二萜是通过1-脱氧-D-木酮糖-5-磷酸途径生物合成的，而不是经典的甲羟戊酸途径。在[1-(13)C;3,4-(2)H2]-1-脱氧-D-木酮糖存在下生长的植物中进一步证实了这一点。此外，对在[Me-(13)C]-甲硫氨酸存在下生长的植物产生的萨尔维诺林A的分析表明，C-4羧基的甲基化是由III型依赖S-腺苷-L-甲硫氨酸的O-甲基转移酶催化的。
