中草藥標準品gentianine, honokiol, wogonin之研究，開發及檢驗技術之研究
陳清漂
東華大學
合成中草藥標準品gentianine、honokiol、wogonin及開發檢驗技術。黃芩素可以苦味酸1為起始物，用重氮甲烷處理，產生2,4,6-三硝基甲氧基苯2，以鈀/碳為催化劑，在60 psi氫氣中將硝基還原成胺基，產生2,4,6-三胺基甲氧基苯3，在鹽酸的醋酸溶液中加熱即可生成2,4,6-三羥基甲氧基苯4，將之與苯甲醯基乙酸乙酯5一起加熱至200oC即可生成漢黃芩素6和oroxylin A (7)。合成Honokiol (和厚朴酚)：取5-溴水楊酸8溶於甲醇中，加入催化量之濃硫酸，產生酯化反應可得5-溴水楊酸甲酯9，緊接著與氯甲基甲基醚作用，將羥基保護成甲氧基甲基醚10，在PdCl2(pddf)催化下與bis(pinacolato)diborane反應產生11，在PdCl2(pddf)催化下與12作用產生13，接著以氫化鋁鋰還原產生14，以HF/Pyridine將TBS保護基切除生成15，將二個羥基以NBS和PPh3處理將之轉變成溴化物16，接著在碘化亞銅(CuI)的催化下與vinylmagnesium bromide反應產生17，以2M鹽酸處理即得Honokiol 18。而化合物12可由4-羥基苯甲酸19製備得到，首先將12以甲醇和催化量濃硫酸處理，即可產生4-羥基苯甲酸甲酯20，再以NBS和HBF4處理可生成3-溴-4-羥基苯甲酸甲酯21，緊接著與氯甲基甲基醚作用，將羥基保護成甲氧基甲基醚22，將22之酯基以DIBAL還原成醇23，而23之羥基以TBS保護即可得到化合物12。
關鍵字：gentianine；honokiol；wogonin；標準品
The preparations of Chinese herbal standard, gentianine, honokiol and wogonin, and the studies of their examing methods.
Chen, Chinpiao
National Dong Hwa University
Abstract The preparations of Chinese herbal standard, gentianine, honokiol and wogonin, and the studies of their examing methods. Wogonin will be prepared stating from picric acid. Picric acid (1) reacts with diazomethane to form 2,4,6-trinitroanisole (2), and then reduces by hydrogenation condition (Pd/C, 60 psi H2) to produce 2,4,6-triaminoanisole (3). Compound 3 heats with hydrochloric acid in acetic acid to give 2,4,6-trihydroxyanosole (4). Compound 4 heats with ethyl benzoylacetate up to 200oC to form wogonin (6) and oroxylin A (7). Honokiol can be prepared from 5-bromosalicylic acid (9). 5-Bromosalicylic acid treats with methanol in acidic condition to form the methyl ester (9), which follow treats with chloromethyl methyl ether to give the ether (10). Compound 10 reacts with bis(pinacolato)diborane by catalyzing with PdCl2(pddf) to give 11, and then reacts with 12 to form 13. The ester group of 13 be reduced to alcohol 14 by using lithium aluminium hydride. Two TBS groups can be cleaved by treating with HF/pyridine to afford 15. Both hydroxyl groups of 15 be converted to bromides by treating with NBS and triphenylphosphine to generate compound 16. Compound 16 reacts with vinylmagnesium bromide and catalyze by CuI to give 17, and then treat with hydrochloric acid to cleave the MOM ethers to produce honokiol 18. Compound 12 will be prepared from 4-hydroxybenzoic acid.
關鍵字：gentianine；honokiol；wogonin；standard
