Smardaesidins A鈥揋, Isopimarane and 20-nor-Isopimarane Diterpenoids from Smardaea sp., a Fungal Endophyte of the Moss Ceratodon purpureus

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• 作者：Xiao-Ning Wang ; Bharat P. Bashyal ; E. M. Kithsiri Wijeratne ; Jana M. U鈥橰en ; Manping X. Liu ; Malkanthi K. Gunatilaka ; A. Elizabeth Arnold ; A. A. Leslie Gunatilaka
• 刊名：Journal of Natural Products
• 出版年：2011
• 出版时间：October 28, 2011
• 年：2011
• 卷：74
• 期：10
• 页码：2052-2061
• 全文大小：421K
• 年卷期：v.74,no.10(October 28, 2011)
• ISSN：1520-6025

文摘

Five new isopimarane diterpenes, smardaesidins A鈥揈 (1鈥?5) and two new 20-nor-isopimarane diterpenes, smardaesidins F (6) and G (7), together with sphaeropsidins A (8) and C鈥揊 (10鈥?b>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-oxoisopimara-7-en-20-oic acid (15). The 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鈥?b>7 and 15 were elucidated using MS and 1D and 2D NMR experiments, while the absolute configurations of the stereocenters of 4 and 6鈥?b>8 were assigned using a modified Mosher鈥檚 ester method, CD spectra, and comparison of specific rotation data with literature values. Compounds 1鈥?b>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 the cytotoxicity assay and inhibited migration of metastatic breast adenocarcinoma (MDA-MB-231) cells at subcytotoxic concentrations.