N‐Bearing Furanone Derivatives from an Endophytic Fungus in Huperzia serrata

Abstract

Two new polyketide derivatives, huaspenones C and D (1 and 2, resp.), were isolated from the cultures of an endophytic fungus Peyronellaea sp. HS-12, derived from the stems of Huperzia serrata. They share N-bearing furan-3(2H)-one backbone, and 2 has an unprecedented furo[3,2-c]pyridine skeleton. Their structures including the absolute configuration were elucidated by extensive spectroscopic analysis combined with quantum-chemical calculations. (2E,4E)-6-hydroxy-2-methylocta-2,4dienoic acid (3), a key intermediate of the biosynthesis of 1 and 2, was also obtained from the endophyte.Introduction. -Endophytic fungi are microorganisms which spend their life cycle, as a whole or partly, colonizing inter-and/or intra-cellularly inside the healthy tissues of their host plant, typically causing no apparent symptoms of disease [1]. The research on endophytes showed that they are potential sources of novel biologically active secondary metabolites for exploitation in medicine, agriculture, and industry [2 -5]. Furthermore, results from many researches indicated that they could metabolize the same substance as their own host plants [6 -8], rendering them an alternative source of plant secondary metabolites.Huperzia serrata, a Chinese folk medicinal herb, is well-known for the discovery of hupzine A, a potent, highly specific, and reversible inhibitor of acetylcholinesterase [9] [10]. In a previous study, two new furan-3(2H)-one derivatives, huaspenones A and B (4 and 5, resp.), were isolated from Aspergillus sp. XW-12 derived from the stems of H. serrata [11] 1 ). In this work, two novel N-containing furan-3(2H)-one derivatives, 1 and 2, were isolated from the rice culture of an endophytic fungus Peyronellaea sp. HS-12 obtained from the stems of H. serrata, together with a key intermediate of the biosynthesis of 1 and 2, i.e., (2E,4E)-6-hydroxy-2-methylocta-2,4-dienoic acid (3). In addition, two known compounds, andrastin A (4) [13] and huaspenone B (5) [11], were also obtained from the endophytic fungus. Their structures were elucidated by NMR spectroscopy, especially 2D-NMR spectra. The absolute configurations of 1 and 2 were determined by CD analysis, combined with quantum-chemical calculation. To the best of our knowledge, huaspenones C and D (1 and 2, resp.) are the first examples of Nbearing furan-3(2H)-one derivatives in nature, and 2 has an unprecedented furo[3,2c]pyridine skeleton.

Discovery of Enzyme Inhibitors from Mangrove Sediment Derived Fungus Trichoderma harzianum SCSIO 41051

“…The 1 H and 13 C NMR data (Table 1) of 1 displayed the presence of a characteristic for a carboxyl (δ C 169.2), a sp 2 quaternary carbon (δ C 126.2), three olefinic methine groups (δ H/C 6.21/143.2, 7.10/137.5, 6.54/124.8), two oxygenated methylene groups (δ H/C 3.88/75.3, 3.49/69.7) and two methyl groups (δ H/C 1.04/19.2, 1.84/12.5). The above data were similar to those of the known compound (2E,4E)-6hydroxy-2-methylocta-2,4-dienoic acid, [15] except for an additional oxygenated methylene carbon signal and the absence of a methine carbon signal. Based on the proton spin coupling system in the 1 H-1 H COSY spectrum (Figure 2) of H 3 -8/H-7/H-6/ H-5/H-4/H-3, the connection fragment from C-3 to C-8 was established.…”

“…As part of our research on discovering structurally novel enzyme inhibitors from mangrove fungi, [10][11][12][13] the fungus strains of Trichoderma harzianum SCSIO 41051, obtained through in situ culture [14] in mangrove sediment, collected from Gaoqiao mangrove wetland in the Zhanjiang coastline of the northern part of Beibu Gulf. Further chemical investigations of their crude extract led to the isolation of 17 compounds, including a new fatty acid derivative (1), night known polyketides (2-10), five known alkaloids (11)(12)(13)(14)(15), and two known sesquiterpenoids (16 and 17) (Figure 1). The in vitro enzyme inhibitory assay showed that compounds 9 and 14 exhibited moderate AChE inhibitory activities and compounds 8 and 9 displayed moderate inhibition on PL.…”

The diversity of endophytic fungi in the above-ground tissue of two Lycopodium species in Poland

“…Budziszewska and Szypuła 2010 ; Chen et al 2011 ; Wang et al 2011 ), and two have been driven by an interest in identifying possible novel bioactive chemical compounds (e.g. Zhu et al 2010 ; Xiang et al 2013 ). Indeed, some endophytic fungi from lycophyte Huperzia serrata that is used in chinese medicine are known to produce bioactive metabolites such as huaspenones, (Xiang et al 2013 ) or huperzine (see Zhu et al 2010 ; Zhang et al 2011 , and literature therein).…”

“…Zhu et al 2010 ; Xiang et al 2013 ). Indeed, some endophytic fungi from lycophyte Huperzia serrata that is used in chinese medicine are known to produce bioactive metabolites such as huaspenones, (Xiang et al 2013 ) or huperzine (see Zhu et al 2010 ; Zhang et al 2011 , and literature therein). Only two studies, by Holm and Holm ( 1981 ) and by Engelhardt ( 1987 ), have been dedicated studying the fungal communities of above-ground organs of Lycopodiaceae.…”

Bioactivity Screening and Chemical Characterization of Biocompound from Endophytic Neofusicoccum parvum and Buergenerula spartinae Isolated from Mangrove Ecosystem

“…and is the first naturally occurring N-bearing furanone derivative reported in nature. This study represents the second report of its kind [ 74 ].…”