Cytotoxic Serratane Triterpenes from Diphasiastrum complanatum with a Hydroxy Group at C-27

Abstract

Four serratane-type triterpenes (1–4) were isolated from D. complanatum. Their chemical structures were elucidated as 14α,15α,20β,21β,24,27α,29-heptahydroxyserrat-3-one (1), 3β,14α,15α,20β,21β,24,27α,29-octahydroxyserratane (2), 3α,14α,20β,21β,24,27α,29-heptahydroxyserratane (3) and 3β,14α,21β,24,27α-pentahydroxyl-serratane-29-yl (E)-p-coumarate (4) by spectroscopic methods (MS, 1D and 2D NMR) and X‐ray crystallography. Interestingly, the most characteristic methylene (C-27) of the serratane ring C was oxidized to a methine. Compound 4 showed significant cytotoxic activity against the human leukemia K562/S and the doxorubicin-resistant K562/R cell lines, but the other compounds were inactive.

Key words

Lycopodiaceae - Diphasiastrum complanatum - serratane‐type - complanatumols A–D - leukemia

References

• 1 Ma X Q, Gang D R. The Lycopodium alkaloids.  Nat Prod Rep. 2004;  21 752-772
• 2 Bhutani K K, Kapoor R, Atal C K. Three bridged 14β, 26-epoxy-C-chomo-pentacycle triterpenes from Primula rosea.  Phytochemistry. 1984;  23 403-406
• 3 Kulshreshtha M J, Kulshreshtha D K, Rastogi R P. Review article: the triterpenoids.  Phytochemistry. 1972;  11 2369-2381
• 4 Ghisalberti E L, DeSouza N J, Rees H H, Goodwin T W. Biosynthesis of the triterpene hydrocarbons of Polypodium vulgare.  Phytochemistry. 1970;  9 1817-1823
• 5 Ageta H, Shiojima K, Masuda K. Fern constituents: onoceroid, onoceradiene, serrtene and onoceranoxide, isolated from lemmaphyllum microphyllum varieties.  Chem Pharm Bull. 1982;  30 2272-2274
• 6 Orhan I, Terzioglu S, Sener B. α-Onocerin: an acetylcholinesterase inhibitor from Lycopodium clavatum.  Planta Med. 2003;  69 265-267
• 7 Tanaka R, Kinouchi Y, Tokuda H, Nishino H, Matsunaga S. Bioactive triterpenoids from the stem bark of Picea glehni.  Planta Med. 2000;  66 630-634
• 8 Tanaka R, Minami T, Ishikawa Y, Tokuda H, Matsunaga S. Cancer chemopreventive activity of serratane-type triterpenoids from Picea jezoensis.  Chem Biodivers. 2004;  1 878-885
• 9 Yan J, Chen B H, Zhang X M, Qiu M H. Three new triterpenoids with serratane-type from Phlegmariurus squarrosus.  Helv Chim Acta. 2006;  89 2975-2980
• 10 Yan J, Zhang X M, Li Z R, Zhou L, Chen J C, Sun L R, Qiu M H. Three new triterpenoids from Lycopodium japonicum Thunb.  Helv Chim Acta. 2005;  88 240-244
• 11 Yan J, Yi P, Chen B H, Lu L, Li Z R, Zhang X M, Zhou L, Qiu M H. Five new serratane triterpenoids with poly-hydroxyl from Diphasiastrum complanatum.  Phytochemistry. 2008;  69 506-510
• 12 Lin Z X, Hoult J R S, Raman A. Sulphorhodamine B assay for measuring proliferation of a pigmented melanocyte cell line and its application to the evaluation of crude drugs used in the treatment of vitiligo.  J Ethnopharmacol. 1999;  66 141-150
• 13 Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Waren T J, Bokesch H, Kenney S, Boyd M R. New colorimetric cytotoxicity assay for anticancerdrug screening.  J Natl Cancer Inst. 1990;  82 1107-1112
• 14 Tanaka R, Tsujimoto K, In Y, Ishida T, Matsunaga S, Terada Y. Structure and stereochemistry of epoxyserratanes from the cuticle of Picea jezoensis var. jezoensis.  J Nat Prod. 2001;  61 1044-1047
• 15 Zhou H, Tan C H, Jiang S H, Zhu D Y. Serratene-type triterpenoids from Huperzia serrata.  J Nat Prod. 2003;  66 1328-1332
• 16 Cai X, Pan D J. Novel pentacycIic triterpene esters of Δ¹⁴-serratene type from Lycopodium obscurum L.  Acta Chim Sin. 1992;  50 60-66
• 17 Zhang Z, Elsohly H N, Jacob M R, Pasco D S, Walker L A, Clark A M. Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum.  J Nat Prod. 2002;  65 979-985
• 18 Haruo S, Kazuo F, Xu G Y, Cao X, Pan D J. Assignment of the ¹H-and ¹³C-NMR spectra of four Lycopodium triterpenoids by the application of new two-dimensional techinique, heteronuclear multiple bond connectivity (HMBC).  Agric Biol Chem. 1988;  52 1797-1801
• 19 Conner A H, Nagasampagi B A, Rowe J W. New serratane triterpenes from western white pine bark.  Tetrahedron. 1984;  40 4217-4226
• 20 Zhou H, Li Y S, Tong X T, Liu H Q, Jiang S H, Zhu D Y. Serratane-type triterpenoids from Huperzia serrata.  Nat Prod Res. 2004;  18 453-459
• 21 Wang X M, Lou H X. Complete NMR chemical shift assignments for three serratane triterpenoids isolated from moss Homalia trichomanoides.  Chin J Magn Reson. 2005;  22 35-41