Microbial transformations of two tetracyclic beyerane-type diterpenes, ent-16β-oxobeyeran-19-oic acid (1) and its chemical reduction product, ent-16β-hydroxybeyeran-19-oic acid (2), by the filamentous fungus Cunninghamella echinulata ATCC 8688a yielded eight metabolites (3-10). Incubation of the substrate 2 with C. echinulata afforded three new hydroxylated ones (3-5) along with two known ones (6-7), while incubation of 1 gave three known ones (8-10). The new compounds were characterized by 1D and 2D NMR as well as HRESIMS analysis, and the stereostructures of 3 and 4 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 2. This is the first report on the biotransformation of the diterpenes by using C. echinulata. All compounds were assayed for their α-glucosidase inhibitory, neurotrophic, anti-inflammatory, and phytotoxic activity, and only in neurotrophic assay compounds, 2 and 9 were found to display nerve growth factor-mediated neurite-outgrowth promoting effects in PC12 cells; the others were inactive.

中文翻译：

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坎宁哈氏菌（Cunninghamella echinulata）对两种拜亚烷型二萜的微生物转化。

两种丝状真菌Cunninghamella echinulata ATCC对两个四环亚苄烷型二萜ent-16β-oxobeyeran-19-oicacid（1）及其化学还原产物ent-16β-hydroxybeyeran-19-oicacid（2）的微生物转化。 8688a产生八种代谢产物（3-10）。将底物2与棘孢梭菌一起温育得到三个新的羟基化的（3-5）以及两个已知的羟基化的（6-7），而温育1得到三个已知的羟基化的（8-10）。通过1D和2D NMR以及HRESIMS分析对新化合物进行了表征，并通过X射线晶体学证实了3和4的立体结构。该生物反应不仅涉及在两个拜亚烷二萜的惰性位置C-7，-9，-12和-14的立体选择性结合羟基，还涉及在C-19为2时的糖苷化反应。这是关于使用松毛线虫对二萜生物转化的首次报道。测定所有化合物的α-葡糖苷酶抑制，神经营养，抗炎和植物毒性活性，仅在神经营养测定化合物中，发现2和9个化合物在PC12细胞中显示出神经生长因子介导的神经突增生作用。其他人则不活跃。