Yang Li-Ming, Hsu Feng-Lin, Cheng Juei-Tang, Chang Cheng-Hao, Liu Pan-Chun, Lin Shwu-Jiuan
Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Planta Med. 2004 Apr;70(4):359-63. doi: 10.1055/s-2004-818949.
ent-16beta-Hydroxybeyeran-19-oic acid ( 1) has potential antihypertensive activity. To obtain novel and more-effective compounds, 1 was incubated with Bacillus megaterium ATCC 14 581 and Aspergillus niger CCRC 32 720. The structures of the metabolites were determined by HR-FAB-MS, 1D- and 2D-NMR spectral data, and enzymatic hydrolysis. Bacillus megaterium hydroxylated and glucosidated 1 to yield ent-7alpha,16beta-dihydroxybeyeran-19-oic acid ( 2), ent-16beta-hydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 3), and ent-7alpha,16beta-dihydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 4). Aspergillus niger hydroxylated 1 to yield ent-1beta,7alpha,16beta-trihydroxybeyeran-19-oic acid ( 5) and ent-1beta,7alpha-dihydroxy-16-oxobeyeran-19-oic acid ( 6). Metabolites 3 - 5 were characterized as new compounds. In addition, 2, 3, 5, and 6 were tested for antihypertensive effects, and we found that 5 and 6 were more potent than the parent compound 1.
对映-16β-羟基贝壳杉烷-19-酸（1）具有潜在的抗高血压活性。为了获得新型且更有效的化合物，将1与巨大芽孢杆菌ATCC 14581和黑曲霉CCRC 32720一起培养。通过高分辨快原子轰击质谱（HR-FAB-MS）、一维和二维核磁共振光谱数据以及酶促水解确定代谢产物的结构。巨大芽孢杆菌使1发生羟基化和葡萄糖苷化反应，生成对映-7α,16β-二羟基贝壳杉烷-19-酸（2）、对映-16β-羟基贝壳杉烷-19-酸α-D-吡喃葡萄糖苷酯（3）和对映-7α,16β-二羟基贝壳杉烷-19-酸α-D-吡喃葡萄糖苷酯（4）。黑曲霉使1发生羟基化反应，生成对映-1β,7α,16β-三羟基贝壳杉烷-19-酸（5）和对映-1β,7α-二羟基-16-氧代贝壳杉烷-19-酸（6）。代谢产物3至5被鉴定为新化合物。此外，对2、3、5和6进行了抗高血压作用测试，我们发现5和6比母体化合物1的活性更强。
