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(+)- and (−)-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452
Tetrahedron Letters xxx (xxxx) xxx
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(+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452 Wei-Mao Zhong a,c, Jun-Feng Wang a, Xiao-Yi Wei b, Qi Zeng a,c, Xia-Yu Chen a,c, Yao Xiang a,c, Xin-Peng Tian a, Si Zhang a, Li-Juan Long a,⇑, Fa-Zuo Wang a,⇑ a CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China b Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, 723 Xingke Road, Guangzhou 510650, China c University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 27 February 2019 Revised 16 April 2019 Accepted 13 May 2019 Available online xxxx
(±)-Eurotone A [(±)-1], a pair of new enantiomeric polyketide dimers, as well as six known biogenetically related polyketides (2–7) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by comprehensive spectroscopic methods, X-ray diffraction and quantum chemical calculations. Compound 1 represented the first pair of spirodihydrobenzanthracene enantiomers isolated from marine fungi with their absolute configurations assigned. A plausible biosynthetic pathway involving a key acid-mediated dimerization was proposed for 1. The antioxidative activities of the new enantiomers were evaluated. Ó 2019 Published by Elsevier Ltd.
Keywords: Marine-derived fungi Polyketide Enantiomeric dimers Structure elucidation
Introduction Marine-derived fungi have received great attention as a promising reservoir for structurally diverse and biologically significant secondary metabolites in recent decades [1,2]. Thousands of natural products have been reported from marine fungi, including meroterpenoids, alkaloids, polyketides, and cyclic peptides, which exhibit different kinds of biological activities such as antiviral, antiinflammatory, and cytotoxic activities [3–6]. Marine fungi derived dimeric polyketides represent a class of natural products that originated from monomer polyketides and generally exhibit a wide range of bioactivities [7–9]. During our endeavors for bioactive metabolites from South China Sea derived fungi, we disclosed a series of compounds with intriguing architectures and activities [10–12]. Prior chemical investigation on a fungus Eurotium sp. SCSIO F452, which was isolated from a South China Sea sediment sample and found to produce diketopiperazine alkaloids, polyketides, especially three pairs of spirocyclic diketopiperazine-anthraquinone enantiomers [13–15]. A further chemical study on the remaining subfraction of its extract afforded a new pair of enantiomeric polyketide dimers (±)-eurotone A [(±)-1], along with a ser-
ies of known polyketides (2–7) (Fig. 1). Herein we report the isolation, structure elucidation, plausible biosynthetic pathway, and antioxidative evaluation of new compounds. Results and discussion (±)-Eurotone A [(±)-1] was obtained as yellow crystals. Its molecular formula was deduced to be C34H28O9 by HRESIMS at
⇑ Corresponding authors. E-mail addresses: (F.-Z. Wang).
[email protected]
(L.-J.
Long),
[email protected] Fig. 1. Chemical structures of compounds (+)-1, (-)-1, and 2–7.
https://doi.org/10.1016/j.tetlet.2019.05.025 0040-4039/Ó 2019 Published by Elsevier Ltd.
Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025
2
W.-M. Zhong et al. / Tetrahedron Letters xxx (xxxx) xxx
m/z 579.1654 [MH] (calcd for 579.1660), corresponding to an index of hydrogen deficiency of 21. The UV spectrum of 1 displayed characteristic absorptions at 208, 277, 323, 372 nm. The 1H NMR (Table 1) spectrum of 1 recorded in CD3COCD3 showed two tertiary methyls at dH 2.13 (s), 2.41 (s), two methoxyls at dH 3.33 (s), 3.76 (s), seven aromatic protons at dH 6.35 (d, J = 1.1 Hz), 6.37 (d, J = 2.5 Hz), dH 6.42 (d, J = 2.5 Hz), dH 6.49 (s), dH 6.66 (s), dH 6.84 (s), dH 7.25 (s), five exchangeable protons at dH 5.20 (br s), 12.36 (br s), 12.69 (br s), 12.83 (br s), and 13.00 (br s). Its 13C NMR and HSQC spectra exhibited a total of 34 carbon resonances divided into 4 methyls (2 oxygenated), 2 aliphatic methylenes, 7 aromatic methines, and 21 nonprotonated carbons (2 carbonyls, 17 aromatic carbons, 1 oxygenated aliphatic carbon, and 1 quaternary carbon). Detailed analysis of its 1D and 2D NMR (Fig. 2) allowed for the assignment of two partial structures 1a and 1b, as well as their connectivity. The 1D NMR data of partial structure 1a displayed high similarities with physcion (2) [16], which was also isolated from this fungus. Their main difference was that a carbonyl (C-10) in physcion was replaced by an oxygenated nonprotonated carbon linking a methylene. This assignment was verified by the key HMBC correlations from H-12a (dH 2.66, dt, J = 14.0, 3.4 Hz) and H-12b (dH 2.29, dt, J = 14.0, 3.4 Hz) to C-10a (dC 147.8), C-4a (dC 145.1), and C-10 (dC 65.8), from 10-OH (dH 5.20, br s) to C-4a, C-10, and C-12 (dC 29.5), from H-4 (dH 7.25, s) to C-10, and C-9a (dC 112.7). The partial substructure 1b was similar to 1a, with the main difference that the oxygenated nonprotonated carbon at C-10 in 1a was replaced by a quaternary carbon at C-100 (dC 46.7) in 1b. This elucidation could be verified by the HMBC correlations from H-40 (dH 6.35, d, J = 1.1 Hz) to C-20 (dC 116.5), C-90 a (dC 111.7), and C-100 ; from H50 (dH 6.42, d, J = 2.5 Hz) to C-80 a (dC 109.0), and C-100 ; from H120 a (dH 2.89, dt, J = 10.5, 3.4 Hz) and H-120 b (dH 1.89, overlap) to C-100 a (dC 159.7), C-40 a (dC 152.7), and C-100 . Hitherto, structure moieties 1a and 1b had occupied twenty degrees of unsaturation, indicating another ring in 1. Detailed analysis of its 2D NMR data revealed that 1a and 1b were connected by C-12–C-120 and C-5–C-100 , forming a cyclohexene ring. This connection could be determined by the key COSY cross peak of H212/H2-120 and diagnostic HMBC correlations from H2-12 to C-100 , from H2-120 to C-5, and C-10. Finally, the planar structure of 1 was established with its trivial name eurotone A. However, the 2D NMR spectra did not provide sufficient information to elucidate the relative configuration of 1. Fortunately, a single crystal of 1
Fig. 2. Key 1H–1H COSY and HMBC correlations of (±)-1.
suitable for X-ray diffraction was obtained (CCDC 1899159, Fig. 3), confirming its planar structure as well as determining its relative configuration as (10S*, 100 S*) unambiguously. Additionally, the crystal of 1 occupied a Pccn space group, indicating its racemic nature, which was also supported by its lack of optical activity. Subsequently, 1 was successfully separated to two optically pure enantiomers [(+)-1 and ()-1] by chiral HPLC (Fig. S2). Furthermore, the quantum calculated electronic circular dichroism (ECD) spectrum at the B3LYP/def2-TZVP level with the PCM model in MeCN for (10S, 100 S)-1 agreed well with the measured one for (+)-1 (Fig. 4). Therefore, the absolute configurations of (+)-1 and ()-1 were unambiguously assigned. The known compounds 2–7 were identified as physcion (2) [16], questin (3) [17], catenarin (4) [17], variecolorquinone B (5) [18], 2-O-methyl-9-dehydroxyeurotinone (6) [19], and 1,6,8-trihydroxy-4-benzoyloxy-3-methylanthraquinone (7) [20] based on the comparison of their spectroscopic data with literatures. Additionally, compound 3 was confirmed by a single-crystal X-ray diffraction experiment (CCDC 1899141, Fig. S1). According to the structure characteristics of (+)-1 and ()-1, they should be polyketide dimers possessing an unusual spirodihydrobenzanthracene carbon skeleton. To the best of our knowledge,
Table 1 H and 13C NMR Data for 1 recorded in CD3COCD3 (700, 175 MHz, TMS, d in ppm).
1
Position 1 2 3 4 4a 5 6 7 8 8a 9 9a 10 10a 11 12 6-OMe 1-OH 8-OH 10-OH
dH (J, Hz) 6.84, s 7.25, s
6.49, s
2.41, s a 2.66, dt (14.0, 3.4) b 2.29, dt (14.0, 3.4) 3.33, s 12.36, br s 13.00, br s 5.20, br s
dC
Position
163.8 118.4 149.5 118.7 145.1 123.6 165.5 102.0 166.4 107.7 192.5 112.7 65.8 147.8 22.3 29.5
10 20 30 40 40 a 50 60 70 80 80 a 90 90 a 100 100 a 110 120
56.3
60 -OMe 10 -OH 80 -OH
dH (J, Hz) 6.66, s 6.35, d (1.1) 6.42, d (2.5) 6.37, d (2.5)
2.13, s a 2.89, dt (10.5, 3.4) b 1.89, overlap 3.76, s 12.69, br s 12.83, br s
dC 164.6 116.5 148.3 118.7 152.7 105.5 167.8 99.1 166.9 109.0 191.9 111.7 46.7 159.7 22.2 40.3 56.0
Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025
W.-M. Zhong et al. / Tetrahedron Letters xxx (xxxx) xxx
Fig. 3. X-ray crystallographic structure of (±)-1.
3
Scheme 1. Proposed biosynthetic pathway of compound (±)-1.
dehydration reaction to give the key intermediate 10-methyleneanthrone II. Then, an acid-mediated nucleophilic addition dimerization between II and III produced the carbocation intermediate IV. A cyclization between C-5 and C-100 occurred by p-system nucleophilic attack on the carbocation at C-100 producing intermediate V, which went through keto-enol tautomerism and oxidation to finally yield (±)-1 (Scheme 1). Compounds (+)-1 and ()-1 were screened for their antioxidative activity against DPPH [26], but neither of them exhibited obvious antioxidative potency (IC50 > 200 mM). In conclusion, a pair of new enantiomeric polyketide dimers, (+)- and ()-eurotone A, representing the first spirodihydrobenzanthracene enantiomers, along with six known biologically related polyketides were isolated from a South China Sea derived fungus Eurotium sp. SCSIO F452. The racemate was confirmed through single crystal X-ray diffraction experiment, and resolved into optically pure enantiomers by chiral HPLC. Their configurations were assigned by ECD quantum chemical calculation. Acknowledgments
Fig. 4. Comparison between calculated and experimental ECD spectra of (±)-1 in MeCN.
spirobenzanthracene derivatives are mainly reported as synthetic chemical entities [21–24], rarely derived as natural products [25]. (+)- and ()-Eurotone A are not only represented the first pair of spirodihydrobenzanthracene enantiomers isolated from marine fungi, but also confirmed their planar structures and absolute configurations by X-ray diffraction experiment, chiral separation, and ECD quantum chemical calculation for the first time. Inspired by the (±)-spirooxanthromicin A [21], we proposed a plausible mechanism with a different polyketide precursor for the biosynthetic pathway of (±)-1, involving a key acid-mediated dimerization step [24]. Firstly, we speculated that the precursor physcion (2) went through a methylation reaction to afford I, which underwent a
This work was financially supported by the National Natural Science Foundation of China (Nos. 41476136, 41776169, 41230962), the National Key Research and Development Program of China (2017YFC0506300), Guangdong Province Science and Technology Plan Project (2015B090904003, 2016A020222010), Pearl River S&T Nova Program of Guangzhou (No. 201710010136). We gratefully acknowledge support from the Guangzhou Branch of the Supercomputing Center of Chinese Academy of Sciences and the analytical facilities in SCSIO. Appendix A. Supplementary data This section includes 1D and 2D NMR spectroscopic data, computational details of the new compound 1, as well as the X-ray crystal data of 1 and 3. Supplementary data to this article can be found online at https://doi.org/10.1016/j.tetlet.2019.05.025. These data include MOL files and InChiKeys of the most important compounds described in this article.
Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025
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Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
(+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452 Wei-Mao Zhong a,c, Jun-Feng Wang a, Xiao-Yi Wei b, Qi Zeng a,c, Xia-Yu Chen a,c, Yao Xiang a,c, Xin-Peng Tian a, Si Zhang a, Li-Juan Long a,⇑, Fa-Zuo Wang a,⇑ a CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China b Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, 723 Xingke Road, Guangzhou 510650, China c University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 27 February 2019 Revised 16 April 2019 Accepted 13 May 2019 Available online xxxx
(±)-Eurotone A [(±)-1], a pair of new enantiomeric polyketide dimers, as well as six known biogenetically related polyketides (2–7) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by comprehensive spectroscopic methods, X-ray diffraction and quantum chemical calculations. Compound 1 represented the first pair of spirodihydrobenzanthracene enantiomers isolated from marine fungi with their absolute configurations assigned. A plausible biosynthetic pathway involving a key acid-mediated dimerization was proposed for 1. The antioxidative activities of the new enantiomers were evaluated. Ó 2019 Published by Elsevier Ltd.
Keywords: Marine-derived fungi Polyketide Enantiomeric dimers Structure elucidation
Introduction Marine-derived fungi have received great attention as a promising reservoir for structurally diverse and biologically significant secondary metabolites in recent decades [1,2]. Thousands of natural products have been reported from marine fungi, including meroterpenoids, alkaloids, polyketides, and cyclic peptides, which exhibit different kinds of biological activities such as antiviral, antiinflammatory, and cytotoxic activities [3–6]. Marine fungi derived dimeric polyketides represent a class of natural products that originated from monomer polyketides and generally exhibit a wide range of bioactivities [7–9]. During our endeavors for bioactive metabolites from South China Sea derived fungi, we disclosed a series of compounds with intriguing architectures and activities [10–12]. Prior chemical investigation on a fungus Eurotium sp. SCSIO F452, which was isolated from a South China Sea sediment sample and found to produce diketopiperazine alkaloids, polyketides, especially three pairs of spirocyclic diketopiperazine-anthraquinone enantiomers [13–15]. A further chemical study on the remaining subfraction of its extract afforded a new pair of enantiomeric polyketide dimers (±)-eurotone A [(±)-1], along with a ser-
ies of known polyketides (2–7) (Fig. 1). Herein we report the isolation, structure elucidation, plausible biosynthetic pathway, and antioxidative evaluation of new compounds. Results and discussion (±)-Eurotone A [(±)-1] was obtained as yellow crystals. Its molecular formula was deduced to be C34H28O9 by HRESIMS at
⇑ Corresponding authors. E-mail addresses: (F.-Z. Wang).
[email protected]
(L.-J.
Long),
[email protected] Fig. 1. Chemical structures of compounds (+)-1, (-)-1, and 2–7.
https://doi.org/10.1016/j.tetlet.2019.05.025 0040-4039/Ó 2019 Published by Elsevier Ltd.
Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025
2
W.-M. Zhong et al. / Tetrahedron Letters xxx (xxxx) xxx
m/z 579.1654 [MH] (calcd for 579.1660), corresponding to an index of hydrogen deficiency of 21. The UV spectrum of 1 displayed characteristic absorptions at 208, 277, 323, 372 nm. The 1H NMR (Table 1) spectrum of 1 recorded in CD3COCD3 showed two tertiary methyls at dH 2.13 (s), 2.41 (s), two methoxyls at dH 3.33 (s), 3.76 (s), seven aromatic protons at dH 6.35 (d, J = 1.1 Hz), 6.37 (d, J = 2.5 Hz), dH 6.42 (d, J = 2.5 Hz), dH 6.49 (s), dH 6.66 (s), dH 6.84 (s), dH 7.25 (s), five exchangeable protons at dH 5.20 (br s), 12.36 (br s), 12.69 (br s), 12.83 (br s), and 13.00 (br s). Its 13C NMR and HSQC spectra exhibited a total of 34 carbon resonances divided into 4 methyls (2 oxygenated), 2 aliphatic methylenes, 7 aromatic methines, and 21 nonprotonated carbons (2 carbonyls, 17 aromatic carbons, 1 oxygenated aliphatic carbon, and 1 quaternary carbon). Detailed analysis of its 1D and 2D NMR (Fig. 2) allowed for the assignment of two partial structures 1a and 1b, as well as their connectivity. The 1D NMR data of partial structure 1a displayed high similarities with physcion (2) [16], which was also isolated from this fungus. Their main difference was that a carbonyl (C-10) in physcion was replaced by an oxygenated nonprotonated carbon linking a methylene. This assignment was verified by the key HMBC correlations from H-12a (dH 2.66, dt, J = 14.0, 3.4 Hz) and H-12b (dH 2.29, dt, J = 14.0, 3.4 Hz) to C-10a (dC 147.8), C-4a (dC 145.1), and C-10 (dC 65.8), from 10-OH (dH 5.20, br s) to C-4a, C-10, and C-12 (dC 29.5), from H-4 (dH 7.25, s) to C-10, and C-9a (dC 112.7). The partial substructure 1b was similar to 1a, with the main difference that the oxygenated nonprotonated carbon at C-10 in 1a was replaced by a quaternary carbon at C-100 (dC 46.7) in 1b. This elucidation could be verified by the HMBC correlations from H-40 (dH 6.35, d, J = 1.1 Hz) to C-20 (dC 116.5), C-90 a (dC 111.7), and C-100 ; from H50 (dH 6.42, d, J = 2.5 Hz) to C-80 a (dC 109.0), and C-100 ; from H120 a (dH 2.89, dt, J = 10.5, 3.4 Hz) and H-120 b (dH 1.89, overlap) to C-100 a (dC 159.7), C-40 a (dC 152.7), and C-100 . Hitherto, structure moieties 1a and 1b had occupied twenty degrees of unsaturation, indicating another ring in 1. Detailed analysis of its 2D NMR data revealed that 1a and 1b were connected by C-12–C-120 and C-5–C-100 , forming a cyclohexene ring. This connection could be determined by the key COSY cross peak of H212/H2-120 and diagnostic HMBC correlations from H2-12 to C-100 , from H2-120 to C-5, and C-10. Finally, the planar structure of 1 was established with its trivial name eurotone A. However, the 2D NMR spectra did not provide sufficient information to elucidate the relative configuration of 1. Fortunately, a single crystal of 1
Fig. 2. Key 1H–1H COSY and HMBC correlations of (±)-1.
suitable for X-ray diffraction was obtained (CCDC 1899159, Fig. 3), confirming its planar structure as well as determining its relative configuration as (10S*, 100 S*) unambiguously. Additionally, the crystal of 1 occupied a Pccn space group, indicating its racemic nature, which was also supported by its lack of optical activity. Subsequently, 1 was successfully separated to two optically pure enantiomers [(+)-1 and ()-1] by chiral HPLC (Fig. S2). Furthermore, the quantum calculated electronic circular dichroism (ECD) spectrum at the B3LYP/def2-TZVP level with the PCM model in MeCN for (10S, 100 S)-1 agreed well with the measured one for (+)-1 (Fig. 4). Therefore, the absolute configurations of (+)-1 and ()-1 were unambiguously assigned. The known compounds 2–7 were identified as physcion (2) [16], questin (3) [17], catenarin (4) [17], variecolorquinone B (5) [18], 2-O-methyl-9-dehydroxyeurotinone (6) [19], and 1,6,8-trihydroxy-4-benzoyloxy-3-methylanthraquinone (7) [20] based on the comparison of their spectroscopic data with literatures. Additionally, compound 3 was confirmed by a single-crystal X-ray diffraction experiment (CCDC 1899141, Fig. S1). According to the structure characteristics of (+)-1 and ()-1, they should be polyketide dimers possessing an unusual spirodihydrobenzanthracene carbon skeleton. To the best of our knowledge,
Table 1 H and 13C NMR Data for 1 recorded in CD3COCD3 (700, 175 MHz, TMS, d in ppm).
1
Position 1 2 3 4 4a 5 6 7 8 8a 9 9a 10 10a 11 12 6-OMe 1-OH 8-OH 10-OH
dH (J, Hz) 6.84, s 7.25, s
6.49, s
2.41, s a 2.66, dt (14.0, 3.4) b 2.29, dt (14.0, 3.4) 3.33, s 12.36, br s 13.00, br s 5.20, br s
dC
Position
163.8 118.4 149.5 118.7 145.1 123.6 165.5 102.0 166.4 107.7 192.5 112.7 65.8 147.8 22.3 29.5
10 20 30 40 40 a 50 60 70 80 80 a 90 90 a 100 100 a 110 120
56.3
60 -OMe 10 -OH 80 -OH
dH (J, Hz) 6.66, s 6.35, d (1.1) 6.42, d (2.5) 6.37, d (2.5)
2.13, s a 2.89, dt (10.5, 3.4) b 1.89, overlap 3.76, s 12.69, br s 12.83, br s
dC 164.6 116.5 148.3 118.7 152.7 105.5 167.8 99.1 166.9 109.0 191.9 111.7 46.7 159.7 22.2 40.3 56.0
Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025
W.-M. Zhong et al. / Tetrahedron Letters xxx (xxxx) xxx
Fig. 3. X-ray crystallographic structure of (±)-1.
3
Scheme 1. Proposed biosynthetic pathway of compound (±)-1.
dehydration reaction to give the key intermediate 10-methyleneanthrone II. Then, an acid-mediated nucleophilic addition dimerization between II and III produced the carbocation intermediate IV. A cyclization between C-5 and C-100 occurred by p-system nucleophilic attack on the carbocation at C-100 producing intermediate V, which went through keto-enol tautomerism and oxidation to finally yield (±)-1 (Scheme 1). Compounds (+)-1 and ()-1 were screened for their antioxidative activity against DPPH [26], but neither of them exhibited obvious antioxidative potency (IC50 > 200 mM). In conclusion, a pair of new enantiomeric polyketide dimers, (+)- and ()-eurotone A, representing the first spirodihydrobenzanthracene enantiomers, along with six known biologically related polyketides were isolated from a South China Sea derived fungus Eurotium sp. SCSIO F452. The racemate was confirmed through single crystal X-ray diffraction experiment, and resolved into optically pure enantiomers by chiral HPLC. Their configurations were assigned by ECD quantum chemical calculation. Acknowledgments
Fig. 4. Comparison between calculated and experimental ECD spectra of (±)-1 in MeCN.
spirobenzanthracene derivatives are mainly reported as synthetic chemical entities [21–24], rarely derived as natural products [25]. (+)- and ()-Eurotone A are not only represented the first pair of spirodihydrobenzanthracene enantiomers isolated from marine fungi, but also confirmed their planar structures and absolute configurations by X-ray diffraction experiment, chiral separation, and ECD quantum chemical calculation for the first time. Inspired by the (±)-spirooxanthromicin A [21], we proposed a plausible mechanism with a different polyketide precursor for the biosynthetic pathway of (±)-1, involving a key acid-mediated dimerization step [24]. Firstly, we speculated that the precursor physcion (2) went through a methylation reaction to afford I, which underwent a
This work was financially supported by the National Natural Science Foundation of China (Nos. 41476136, 41776169, 41230962), the National Key Research and Development Program of China (2017YFC0506300), Guangdong Province Science and Technology Plan Project (2015B090904003, 2016A020222010), Pearl River S&T Nova Program of Guangzhou (No. 201710010136). We gratefully acknowledge support from the Guangzhou Branch of the Supercomputing Center of Chinese Academy of Sciences and the analytical facilities in SCSIO. Appendix A. Supplementary data This section includes 1D and 2D NMR spectroscopic data, computational details of the new compound 1, as well as the X-ray crystal data of 1 and 3. Supplementary data to this article can be found online at https://doi.org/10.1016/j.tetlet.2019.05.025. These data include MOL files and InChiKeys of the most important compounds described in this article.
Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025
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Please cite this article as: W.-M. Zhong, J. F. Wang, X. Y. Wei et al., (+)- and ()-Eurotone A: A pair of enantiomeric polyketide dimers from a marine-derived fungus Eurotium sp. SCSIO F452, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.05.025