Atractylodimers A−D, unprecedented sesquiterpenoid dimers with cage-like skeletons from Atractylodes macrocephala and their neuroprotective activities

Bei Li; Shiqi Zhou; Wei Wu; Yulu Tian; Yating Ren; Jie Ma; Yingda Zang; Yuhe Yuan; Dongming Zhang; Chuangjun Li

doi:10.1016/j.cjnm.2025.100010

Chinese Journal of Natural Medicines ›› 2025, Vol. 23 ›› Issue (12) :100010 -100010. DOI: 10.1016/j.cjnm.2025.100010

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Atractylodimers A−D, unprecedented sesquiterpenoid dimers with cage-like skeletons from Atractylodes macrocephala and their neuroprotective activities

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Abstract

Atractylodimers A−D (1−4), sesquiterpenoid dimers (SDs) featuring a unique cage-like structure, were isolated from the rhizomes of Atractylodes macrocephala. The most distinctive characteristic of these isolates was the highly twisted “cap” structure based on highly twisted five-membered oxygen heterocyclic rings. Notably, compound 1 contained a furo[2,3b]furan ring, a caged 3,10-oxa-tricyclo[5.2.1.0^4,9]decane moiety, and 6/6/5/5/5/5/6/6 octocyclic skeleton. Compounds 2−3 exhibited a spiro-tetrahydrofuran ring, while compound 4 incorporated a caged spiro-2,5,9-oxa-tricyclo[5.2.1.0^4,10]decane scaffold for unit linkage. Their structures were definitively established through spectroscopic methods and X-ray diffraction experiments. Plausible biosynthetic pathways of compounds 1−4 were proposed. Compounds 1 and 2 demonstrated significant neuroprotective effects against serum deprivation-induced PC12 cell damage.

Keywords

Sesquiterpenoid dimers / Caged polycyclic skeleton / Atractylodes macrocephala / X-ray diffraction / Neuroprotective activities

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Bei Li, Shiqi Zhou, Wei Wu, Yulu Tian, Yating Ren, Jie Ma, Yingda Zang, Yuhe Yuan, Dongming Zhang, Chuangjun Li. Atractylodimers A−D, unprecedented sesquiterpenoid dimers with cage-like skeletons from Atractylodes macrocephala and their neuroprotective activities. Chinese Journal of Natural Medicines, 2025, 23(12): 100010-100010 DOI:10.1016/j.cjnm.2025.100010

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References

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[1]	Luo Z, Yin F, Wang X, et al. Progress in approved drugs from natural product resources. Chin J Nat Med. 2024; 22(3):195-211. https://doi.org/10.1016/s1875-5364(24)60582-0.

[2]	Zhan ZJ, Ying YM, Ma LF, et al. Natural disesquiterpenoids. Nat Prod Rep. 2011; 28(3):594. https://doi.org/10.1039/c0np00050g.

[3]	Su LH, Li TZ, Ma YB, et al. Artematrovirenolides A—D and artematrolides S—Z, sesquiterpenoid dimers with cytotoxicity against three hepatoma cell lines from Artemisia atrovirens. Chin J Chem. 2022; 40(1):104-114. https://doi.org/10.1002/cjoc.202100528..

[4]	Shao Z, Li L, Zheng Y, et al. Anti-inflammatory sesquiterpenoid dimers from Artemisia atrovirens. Fitoterapia. 2022;159:105199. https://doi.org/10.1016/j.fitote.2022.105199..

[5]	Sun Y, Chi J, Zhang L, et al. Sarglaromatics A-E: a class of naphthalene-like architecture fused norlindenane sesquiterpene dimers from Sarcandra glabra. J Org Chem. 2022; 87(6):4323-4332. https://doi.org/10.1021/acs.joc.2c00014..

[6]	Li YT, Li SF, Lei C, et al. Dimeric sesquiterpenoids and anti-inflammatory constituents of Sarcandra glabra. Bioorg Chem. 2022;124:105821. https://doi.org/10.1016/j.bioorg.2022.105821..

[7]	Wang YF, Fu Y, Ji YN, et al. Sesquiterpene lactone dimers from the fruit of Carpesium abrotanoides L. Phytochemistry. 2022;203:113389. https://doi.org/10.1016/j.phytochem.2022.113389..

[8]	He XF, Li QH, Li TZ, et al. Artemeriopolides A-D, two types of sesquiterpenoid dimers with rare carbon skeletons from Artemisia eriopoda and their antihepatoma cytotoxicity. Org Chem Front. 2023; 10(11):2635-2641. https://doi.org/10.1039/D3QO00223C.

[9]	Ma LF, Chen YL, Shan WG, et al.Natural disesquiterpenoids: an update. Nat Prod Rep. 2020; 37(7):999-1030. https://doi.org/10.1039/c9np00062c.

[10]	Ma YH, Dou XX, Tian XH. Natural disesquiterpenoids: an overview of their chemical structures, pharmacological activities, and biosynthetic pathways. Phytochem Rev. 2020; 19(4):983-1043. https://doi.org/10.1007/s11101-020-09698-1..

[11]	Zhao WY, Yan JJ, Liu TT, et al. Natural sesquiterpenoid oligomers: a chemical perspective. Eur J Med Chem. 2020;203:112622. https://doi.org/10.1016/j.ejmech.2020.112622..

[12]	Liu B, Fu S, Zhou C. Naturally occurring [4 + 2] type terpenoid dimers: sources, bioactivities and total syntheses. Nat Prod Rep. 2020; 37(12):1627-1660. https://doi.org/10.1039/C9NP00037B.

[13]	Zhu B, Zhang QL, Hua JW, et al. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz: a review. J Ethnopharmacol. 2018; 226:143-167. https://doi.org/10.1016/j.jep.2018.08.023..

[14]

Qian Y, Li W, Wang H, et al. A four-dimensional separation approach by offline 2D-LC/IM-TOF-MS in combination with database-driven computational peak annotation facilitating the in-depth characterization of the multicomponents from Atractylodis macrocephalae Rhizoma (Atractylodes macrocephala). Arab J Chem. 2021; 14(2):102957. https://doi.org/10.1016/j.arabjc.2020.102957..

[15]	Bailly C. Atractylenolides, essential components of Atractylodes-based traditional herbal medicines: Antioxidant, anti-inflammatory and anticancer properties. Eur J Pharmacol. 2021;891:173735. https://doi.org/10.1016/j.ejphar.2020.173735..

[16]	Kim HY, Kim JH. Sesquiterpenoids isolated from the rhizomes of genus Atractylodes. Chem Biodivers. 2022; 19(12):e202200703. https://doi.org/10.1002/cbdv.202200703..

[17]	Li B, Tian Y, Guo X, et al. Atramacrolodes A-D (1-4), four undescribed eudesmane-type sesquiterpenes from the rhizome of Atractylodes macrocephala. Chem Biodivers. 2024; 21(8):e202400817. https://doi.org/10.1002/cbdv.202400817..

[18]	Gong WX, Zhou YZ, Qin XM, et al. Involvement of mitochondrial apoptotic pathway and MAPKs/NF-κB inflammatory pathway in the neuroprotective effect of atractylenolide III in corticosterone-induced PC12 cells. Chin J Nat Med. 2019; 17(4):264-274. https://doi.org/10.1016/s1875-5364(19)30030-5.

[19]	Ji ZH, Liu C, Zhao H, et al. Neuroprotective effect of biatractylenolide against memory impairment in d-galactose-induced aging mice. J Mol Neurosci. 2015; 55(3):678-683. https://doi.org/10.1007/s12031-014-0407-3..

[20]	Rudi A, Erez Y, Benayahu Y, et al. Omriolide A and B; two new rearranged spongian diterpenes from the marine sponge Dictyodendrilla aff. retiara. Tetrahedron Lett. 2005; 46(49):8613-8616. https://doi.org/10.1016/j.tetlet.2005.09.047..

[21]	Rashid S, Bhat BA, Mehta G. Regenerative γ-lactone annulations: a modular, iterative approach to oligo-tetrahydrofuran molecular stairs and related frameworks. Org Lett. 2015; 17(14):3604-3607. https://doi.org/10.1021/acs.orglett.5b01707..

[22]	Xu H, Dickschat JS. Germacrene A-a central intermediate in sesquiterpene biosynthesis. Chemistry A European J. 2020; 26(72):17318-17341. https://doi.org/10.1002/chem.202002163.

[23]	Chen LG, Jan YS, Tsai PW, et al. Anti-inflammatory and antinociceptive constituents of Atractylodes japonica koidzumi. J Agric Food Chem. 2016; 64(11):2254-2262. https://doi.org/10.1021/acs.jafc.5b05841..

[24]	Zhang H, Li J, Si J, et al. Atramacronoids A-C, three eudesmanolide sesquiterpene-phenol hybrids with an unprecedented C-C linkage from the rhizomes of Atractylodes macrocephala. Chin Chem Lett. 2023; 34(1):107743. https://doi.org/10.1016/j.cclet.2022.107743..