Published May 31, 2021
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Bioactive metabolites from the desert plant-associated endophytic fungus Chaetomium globosum (Chaetomiaceae)
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- 1. * & Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese
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Zhang, Xiao-Yan, Tan, Xiang-Mei, Yu, Meng, Yang, Jian, Sun, Bing-Da, Qin, Jian-Chun, Guo, Lan-Ping, Ding, Gang (2021): Bioactive metabolites from the desert plant-associated endophytic fungus Chaetomium globosum (Chaetomiaceae). Phytochemistry (112701) 185: 1-7, DOI: 10.1016/j.phytochem.2021.112701, URL: http://dx.doi.org/10.1016/j.phytochem.2021.112701
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- urn:lsid:plazi.org:pub:0D12845AFFEB0A769B6FC10CF922FF9C
References
- The relative configuration of 1 was determined by NOESY correlations (Fig. 2). The NOESY correlations from 15-OH to 6-Me ' confirmed that 15-OH and the aliphatic chain at C-2' were on the same face of the pyrrolidine-2,4-dione ring and that 6-Me ' and 15-OH were close spatially, allowing determination of the relative configuration of the tetrameric acid ring system (Fig. 2). As the left part in 1 exhibited the same structure and nearly the same chemical shift values as those of 3, which was co-isolated from the same fungus, the stereochemistry of C-7 in 1 was suggested to be R (Fig. 3). The absolute configuration of 1 was established by ECD experiments combined with time-dependent density functional theory (TDDFT)-based quantum-chemical calculations (Frisch et al., 2009; MOE 2009.10, http://www.chemcomp.com). According to the results of NOESY correlations, there exist two possible structures with different absolute configurations (1a and 1b). The simulated spectra of the conformers were averaged according to Boltzmann distribution theory and their relative Gibbs free energy (Δ G) values (Frisch et al., 2009; MOE 2009.10, http://www. chemcomp. com). The theoretical ECD spectrum of the corresponding enantiomer was obtained by directly inverting the ECD spectrum of the calculated model molecule. By comparing the experimental spectrum with the calculated ECD spectra (Fig. 4), the stereochemistry of 1 was concluded to be that of 1a.
- The molecular formula of globosumone (2) was determined to be C24H27ClO7 on the basis of the HRESIMS data (m/z 463.1524 [M+H]+; Calcd 463.1524) with 11 degrees of unsaturation, which is one less than that of chaetoviridine E (4) (Chen et al., 2012). A comparison of the 1H NMR spectra of 2 and 4 revealed that the H-1 (δ H = 8.78 ppm) in 4 disappeared, whereas two additional peaks were observed at δ H =5.30 ppm and 3.08 ppm (-OCH3). These results implied that the double bond might be oxygenated and methylated to form hemiacetal and hydroxyl or hydroxymethyl groups at C-1 and C-8a, respectively. The HMBC correlations from -OCH3 to C-1 and from H-1 to -OCH3 and C-8a confirmed that -OCH3 was connected to C-1 (Fig. 2). Considering the chemical shift value and molecular formula, the remaining hydroxyl group was determined to be linked at C-8a. This hypothesis was also supported by the NMR spectra of 2 in DMSO -d6. The 1H NMR spectra of 2 in both deuterated solvents (CDCl3 and DMSO -d6) were nearly the same except that an additional singlet signal (δ H =7.47 ppm) was observed in the DMSO -d6 spectrum, and its lack of correlation with any carbon in the HMQC spectrum confirmed it to be a hydroxyl group. The HMBC correlations from the signal at δ H = 7.47 ppm to C-1, C-4a, C-8 and C-8a demonstrated that this hydroxyl group was connected to C-8a. Thus, the planar structure of 2 was determined. Structurally, compound 2 might come from 4 by a series of post-modification reactions, including oxygenation, hydration and methylation at double bonds C-1 and C-8a. Thus, 2 possessed the same configuration as chaetoviridine E (4) except at C-1 and C-8a. The NOESY correlations from 8a-OH to 7-CH3 and H-1 revealed that these protons all adopted β -configurations. The absolute configuration of C-7 in azaphilones is usually determined by circular dichroism (Zhang et al., 2012; Li et al., 2014). The CD spectrum of compound 2 was nearly the same as those of chaetoviridine E (4) (Phonkerd et al., 2008; Chen et al., 2012), chaetoviridin A (5) (Takahashi et al., 1990), and chaetoviridide A-C (Wang et al., 2018), resulting in assignment of the S -configuration of C-7 in 2, and then the stereochemistry of C-1 and C-8a was established as S and S, respectively (Fig. 5).
- The phytotoxin spiciferone A (3) and its analogues were isolated from plant pathogens. The unique carbon skeleton of 3 implied its unusual biosynthetic pathway, which has not been elucidated to date, although a key retro-aldol reaction was suggested for its PKS biosynthesis (Tan et al., 2018; Nakajima et al., 1989, 1994). The tetramic acid ring is formed via a PKS-NRPS pathway and constitutes the key skeleton of many fungal metabolites (Schobert and Schlenk, 2008; Boettger and Hertweck, 2013). The structure of 1 contains a spiciferone A (3) unit and a tetramic acid ring linked by a carbon-carbon bond (between C-9 and C-15), which has not previously been encountered in nature. The structural features imply an unusual biogenetic pathway of 1: a PKS-PKS-NRPS hybrid route. First, a PKS synthase biosynthesizes a polyketide intermediate (1A) to form phytotoxin spiciferone A (3) by a unique retro -aldol reaction (Tan et al., 2018; Nakajima et al., 1989, 1994). Another NRPS-PKS megasynthase biogenetically synthesizes the tetramic acid ring, which is subsequently oxygenated to be form intermediate 1B. Condensation and dehydration from 1A and 1B then form the unique structure of 1 (Fig. 6). Azaphilones are abundant polyketides isolated from different fungal resources, but globosumone (2) possesses a 1-OMe unit and an 8a-OH group, which might originate from 7-epi--chaetoviridin E (4) by oxidation. This is the first report of this undescribed compound despite previous reports of more than 400 azaphilone analogues (Gao et al., 2013).