Smardaesidins A-G, isopimarane and 20-nor-isopimarane diterpenoids from Smardaea sp., a fungal endophyte of the moss Ceratodon purpureus.
Smardaesidins A-G, isopimarane and 20-nor-isopimarane diterpenoids from Smardaea sp., a fungal endophyte of the moss Ceratodon purpureus.
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DOI：
10.1021/np2000864
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发表时间：
2011-10-28
影响因子：
5.1
通讯作者：
Gunatilaka AA
中科院分区：
文献类型：
--
作者：
Wang XN;Bashyal BP;Wijeratne EM;U'Ren JM;Liu MX;Gunatilaka MK;Arnold AE;Gunatilaka AA
从一株内生真菌中分离得到5个新的异海松烷二萜，分别为smardaesidins A-E（1 - 5）和2个新的20-去甲异海松烷二萜，smardaesidins F（6）和G（7），以及sphaeropsidins A（8）和C-F（10 - 13）。其中，以不可分离的异构体混合物的形式获得smardaesidin B（2）和C（3）。Sphaeropsidin A（8）经化学还原得到Sphaeropsidin B（9），而8经催化氢化得到7-O-15，16-四氢Sphaeropsidin A（14）及其新衍生物7-羟基-6-氧代-异海松-7-烯-20-酸（15）。经乙酰化和重氮甲烷化反应，分别得到6-O-乙酰基sphaeropsidin A（16）和8，14-亚甲基sphaeropsidin A甲酯（17）。10的甲基化产生Sphaeropsidin C甲酯（18）。通过MS、1D和2D NMR实验确定了新化合物1 - 7和15的平面结构和相对构型，并通过改进的Mosher酯法、圆二色性光谱和比旋光度数据与文献值的比较确定了化合物4和6 - 8的立体中心的绝对构型。使用几种癌细胞系和来源于正常人原代成纤维细胞的细胞评价化合物1 - 18的潜在抗癌活性。其中，化合物8、11和16显示出显著的细胞毒活性。更重要的是，球壳孢菌素A（8）在细胞毒性试验中显示出细胞类型选择性，并在亚细胞毒性浓度下抑制转移性乳腺癌（MDA-MB-231）细胞的迁移。
Five new isopimarane diterpenes, smardaesidins A – E (1 – 5) and two new 20-nor-isopimarane diterpenes, smardaesidins F (6) and G (7) together with sphaeropsidins A (8), and C – F (10 – 13) were isolated from an endophytic fungal strain, Smardaea sp. AZ0432, occurring in living photosynthetic tissue of the moss Ceratodon purpureus. Of these, smardaesidins B (2) and C (3) were obtained as an inseparable mixture of isomers. Chemical reduction of sphaeropsidin A (8) afforded sphaeropsidin B (9) whereas catalytic hydrogenation of 8 yielded 7-O-15,16-tetrahydrosphaeropsidin A (14), and its new derivative, 7-hydroxy-6-oxo-isopimara-7-en-20-oic acid (15). Acetylation and diazomethane reaction of sphaeropsidin A (8) afforded two of its known derivatives, 6-O-acetylsphaeropsidin A (16) and 8,14-methylenesphaeropsidin A methyl ester (17), respectively. Methylation of 10 yielded sphaeropsidin C methyl ester (18). The planar structures and relative configurations of the new compounds 1 – 7, and 15 were elucidated using MS, and 1D and 2D NMR experiments while the absolute configurations of the stereocenters of 4 and 6 – 8 were assigned using modified Mosher’s ester method, CD spectra, and comparison of specific rotation data with literature values. Compounds 1 – 18 were evaluated for their potential anticancer activity using several cancer cell lines and cells derived from normal human primary fibroblasts. Of these, compounds 8, 11, and 16 showed significant cytotoxic activity. More importantly, sphaeropsidin A (8) showed cell-type selectivity in cytotoxicity assay and inhibited migration of metastatic breast adenocarcinoma (MDA-MB-231) cells at sub-cytotoxic concentrations.
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影响因子：
5.8
作者：
Posada, D;Crandall, KA
通讯作者：
Crandall, KA
DOI：
10.1073/pnas.2533483100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Arnold, AE;Mejía, LC;Herre, EA
通讯作者：
Herre, EA
影响因子：
11.5
作者：
Ehlers, JP;Worley, L;Harbour, JW
通讯作者：
Harbour, JW
影响因子：
3.8
作者：
Evidente, A;Sparapano, L;Motta, A
通讯作者：
Motta, A
影响因子：
3.8
作者：
Evidente, A;Sparapano, L;Frisullo, S
通讯作者：
Frisullo, S