Glasesterterpenoids A−C: three sesterterpenoids with 7-cyclohexyldecahydronaphthalene carbon skeleton isolated from the root of Lindera glauca

Abstract

Three novel sesterterpenoids glasesterterpenoids A−C (1−3), featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton, were isolated from the root of Lindera glauca (L. glauca). Their structures were elucidated by quantum chemical calculations and spectroscopic methods. The biogenetic pathway for 1−3 is proposed. In the bioassay, glasesterterpenoid C exhibited DNA topoisomerase 1 (Top1) inhibitory activity compared with the positive control, camptothecin. These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L. glauca.

Keywords

Sesterterpenoids / Lindera glauca

References

[1] Li K, Gustafson KR. Sesterterpenoids: chemistry, biology, and biosynthesis[J]. Nat Prod Rep, 2021, 38 (7): 1251-1281.

[2] Teng LL, Mu RF, Liu YC, et al. Immunosuppressive and adipogenesis inhibitory sesterterpenoids with a macrocyclic ether system from Eurysolen gracilis[J]. Org Lett, 2021, 23 (6): 2232-2237.

[3] Luo SH, Luo Q, Niu XM, et al. Glandular trichomes of Leucosceptrum canum harbor defensive sesterterpenoids[J]. Angew Chem Int Edit, 2010, 49 (26): 4471-4475.

[4] Ruan QF, Jiang SQ, Zheng XY, et al. Pseudoguaianelactones A-C: three unusual sesquiterpenoids from Lindera glauca with anti-inflammatory activities by inhibiting the LPS-induced expression of iNOS and COX-2[J]. Chem Commun, 2020, 56 (10): 1517-1520.

[5] Ruan QF, Pan WC, Zhao M, et al. Butyrolactone and sesquiterpene derivatives as inhibitors of iNOS from the roots of Lindera glauca[J]. Bioorg Chem, 2021, 111 : 104871.

[6] Chen ZL, Chen XC, Tang YQ, et al. Linderasesterterpenoids A and B: two 7-cyclohexyldecahydroazulene carbon skeleton sesterterpenoids isolated from the root of Lindera glauca[J]. Org Lett, 2022, 24 (20): 3717-3720.

[7] Luo SH, Weng LH, Xie MJ, et al. Defensive sesterterpenoids with unusual antipodal cyclopentenones from the leaves of Leucosceptrum canum[J]. Org Lett, 2011, 13 (7): 1864-1867.

[8] Hu DX, Tang WL, Zhang Y, et al. Synthesis of methoxy-, methylenedioxy-, hydroxy-, and halo-substituted benzophenanthridinone derivatives as DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors and their biological activity for drug-resistant cancer[J]. J Med Chem, 2021, 64(11): 7617-7629.

Funding

National Natural Science Foundation of China(82104524)

Basic and Applied Research Program of Guangzhou City(2024A04J9954)