Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China.
School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
J Agric Food Chem. 2020 Apr 22;68(16):4624-4631. doi: 10.1021/acs.jafc.0c00592. Epub 2020 Apr 13.
Microbial transformations of two tetracyclic beyerane-type diterpenes, -16β-oxobeyeran-19-oic acid () and its chemical reduction product, -16β-hydroxybeyeran-19-oic acid (), by the filamentous fungus ATCC 8688a yielded eight metabolites (). Incubation of the substrate with afforded three new hydroxylated ones () along with two known ones (-), while incubation of gave three known ones (). The new compounds were characterized by 1D and 2D NMR as well as HRESIMS analysis, and the stereostructures of and were confirmed by X-ray crystallography. The bioreactions were involved not only in stereoselective incorporation of hydroxyl groups at inert positions C-7, -9, -12, and -14 of the two beyerane diterpenes but also in glucosidation at C-19 of . This is the first report on the biotransformation of the diterpenes by using . All compounds were assayed for their α-glucosidase inhibitory, neurotrophic, anti-inflammatory, and phytotoxic activity, and only in neurotrophic assay compounds, and were found to display nerve growth factor-mediated neurite-outgrowth promoting effects in PC12 cells; the others were inactive.
一株丝状真菌 ATCC 8688a 对两种四环倍半萜别海松烷型二萜，-16β-氧代别海松-19-酸（）及其化学还原产物，-16β-羟基别海松-19-酸（）进行了微生物转化，生成了八种代谢产物（）。将底物与孵育得到三种新的羟基化产物（），加上两种已知产物（），而孵育则得到三种已知产物（）。新化合物通过 1D 和 2D NMR 以及 HRESIMS 分析进行了表征，和的立体结构通过 X 射线晶体学得到了证实。生物反应不仅涉及到两个别海松烷二萜在惰性位置 C-7、-9、-12 和 -14 上的立体选择性羟基化，还涉及到在 C-19 上的葡萄糖苷化。这是首次报道使用对二萜进行生物转化。所有化合物都进行了 α-葡萄糖苷酶抑制、神经营养、抗炎和植物毒性活性测试，只有在神经营养测试中，和显示出对 PC12 细胞中神经生长因子介导的神经突生长促进作用；其他则没有活性。
