Ten ring-B aromatized ergosterols from Aspergillus spectabilis

Abstract

Spectasterols F−O (1−10), ten interesting ergosterols with an aromatized B ring, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, single-crystal X-ray diffraction analyses, and electronic circular dichroism (ECD) calculations. Structurally, these aromatic ergosterols feature versatile side chains. Notably, compound aromatic ergosterols featured versatile side chains, and compound 4 is an unusual C23 ergosterol characterized by a shorter side chain due to oxidative cleavage between C-23 and C-24. All compounds were evaluated for their neuroprotective activities, with compound 8 showing a dose-dependent ability to reduce apoptosis and protect mitochondrial function in glutamate-induced SH-SY5Y cells.

Keywords

Steroids / Aspergillus spectabilis / Aromatic ergosterols / Neuroprotective activities / Structure elucidation

References

[1] Dembitsky VM, Savidov N, Poroikov VV, et al. Naturally occurring aromatic steroids and their biological activities[J]. Appl Microbiol Biotechnol, 2018, 102(11): 4663-4674.

[2] Heller M, Lenhard RH, Bernstein S. Substituted ring AB aromatic steroids[J]. J Am Chem Soc, 1967, 89(8): 1919-1925.

[3] Chatterjee A, Chaudhuri SRR, Chatterjee SK. Stereospecif cis-reduction of hexahydro-3-oxophenanthrene derivatives. Total synthesis of a new class of ring-c aromatic steroid[J]. J Chem Soc Chem Comm, 1982, 1982: 24-25.

[4] Hussler G, Albrecht P. C27-C29 monoaromatic anthrasteroid hydrocarbons in Cretaceous black shales[J]. Nature, 1983, 304: 262-263.

[5] Bisseret P, Adam H, Rohmer M. Structural elucidation of ring B aromatic sterols of the soil amoeba Acanthamoeba polyphaga[J]. J Chem Soc Chem Commun, 1987, 9: 693-695.

[6] Barrero AF, Oltra JE, Poyatos JA, et al. Phycomysterols and other sterols from the Fungus Phycomyces blakesleeanus[J]. J Nat Prod, 1998, 61(12): 1491-1496.

[7] Liu XH, Miao FP, Liang XR, et al. Ergosteroid derivatives from an algicolous strain of Aspergillus ustus[J]. Nat Prod Res, 2014, 28(15): 1182-1186.

[8] Zhang W, Draeger S, Schulz B, et al. Ring B aromatic steroids from an endophytic fungus, Colletotrichum sp.[J]. Nat Prod Commun, 2009, 4(11): 1449-1454.

[9] Khayat MT, Ibrahim SRM, Mohamed GA, et al. Anti-inflammatory metabolites from endophytic fungus Fusarium sp.[J]. Phytochem Lett, 2019, 29: 104-109.

[10] Nakada T, Yamamura S. Three new metabolites of hybrid strain KO 0231, derived from Penicillium citreo-viride IFO 6200 and 4692[J]. Tetrahedron, 2000, 56(17): 2595-2602.

[11] Ondeyka JG, Jayasuriya H, Herath KB, et al. Steroidal and triterpenoidal fungal metabolites as ligands of liver X receptors[J]. J Antibiot, 2005, 58(9): 559-565.

[12] Wei MS, Huang LP, Li Q, et al. Spectasterols, aromatic ergosterols with 6/6/6/5/5, 6/6/6/6, and 6/6/6/5 ring systems from Aspergillus spectabilis[J]. J Nat Prod, 2023, 86(6): 1385-1391.

[13] Gawas D, Garcia R, Huch V, et al. A highly conjugated dihydroxylated C28 steroid from a myxobacterium[J]. J Nat Prod, 2011, 74(5): 1281-1283.

[14] Luo Q, Yang ZL, Yan YM, et al. Ganotheaecolin A, a neurotrophic conjugated ergosterol with a naphtho[1, 8-ef]azulene scaffold from Ganoderma theaecolum[J]. Org Lett, 2017, 19(3): 718-721.

[15] Zhao ZZ, Chen HP, Wu B, et al. Matsutakone and matsutoic acid, two (nor) steroids with unusual skeletons from the edible mushroom Tricholoma matsutake[J]. J Org Chem, 2017, 82(15): 7974-7979.

[16] Liang Y, Li LQ, Shen Y, et al. Four undescribed ergostane-type steroids from Lasiodiplodia pseudotheobromae and their neuroprotective activity[J]. Phytochemistry, 2022, 201: 113248.

Funding

National Key Research and Development Program of China(2021YFA0910500)

National Natural Science Foundation of China(U22A20380)

National Natural Science Foundation of China(82104043)

Innovative Research Groups of the National Natural Science Foundation of China(81721005)

Science and Technology Major Project of Hubei Province(2021ACA012)