Gloeophyllins A–J, Cytotoxic Ergosteroids with Various Skeletons from a Chinese Tibet Fungus Gloeophyllum abietinum

Abstract

Ten new ergosteroids, gloeophyllins A-J (1-10), have been isolated from the solid cultures of Gloeophyllum abietinum. The absolute configurations of 1, 2, and 9 were determined by X-ray crystallographic analysis. Compound 1 has a rare C-nor-D-homosteroid skeleton. Compound 9 possesses an unusual ergostane skeleton having a 10-oxabicyclo [4.3.1] decane moiety replacing 6/5 fused C/D rings. Compound 10 represents the first ergosteroid featuring the cleavage of a C8-C14 bond. The cytotoxicity of 1-10 was tested against the human cancer cell lines K562 and HCT116. The biosynthetic pathway for 1-10 is postulated.

Lanostane Triterpenes from Gloeophyllum odoratum and Their Anti-Influenza Effects

“…Additionally, the13 C NMR and APT spectra of 2 show one oxygenated methine at δ C 76.5 (C-3) and one carboxylic moiety at δ C 181.7 (C-28) in its structure. As reported for gloeophyllin A (5)[18], the interpretation of the 1 H− 1 H COSY and the HMBC data confirmed the presence of a rare 6/6/5/6 ring system, a so called C-nor-D-homoergosteroid skeleton.The configurations of the methyl group at C-29 and the hydroxyl group in C-3 were found to be β oriented by NOEs of H-19/H-29 and H-3/H-5, respectively. The configurations at C-12, C-14, and C-17 were assigned via NOE correlations between H-12/H-14 and H-12/H-17, proving an α orientation of H-12, H-14, and H-17.…”

“…The full assignments of the 13 Triterpenes with this rare and unusual backbone have only been reported once from a fungal source (i.e., Gloeophyllum abietinum grown in Tibet) [18]. Biosynthetically, it is assumed that C-nor-D-homoergosteroids arise via a Wagner-Meerwein rearrangement reaction from a classical lanostane triterpene precursor.…”

“…The six known lanostane triterpenoids were identified by comparing their spectroscopic and spectrometric data (1D and 2D NMR and HRESIMS) with those in the literature: trametenolic acid B (3) [19], gloeophyllin B (4) [18], gloeophyllin A (5) [18], ergosterol peroxide (6) [20], eburicodiol (7) [21], and 21-hydroxylanosterol (8) [22]. Copies of the original spectra for known compounds are obtainable from the corresponding author.…”

Chemical diversity from the Tibetan Plateau fungi Penicillium kongii and P. brasilianum

“…In the past few years, a series of bioactive molecules or new skeletons has been isolated from Tibetan Plateau origin fungi, such as phaeolschidins, with antioxidant activity, from Phaeolus schweinitzii (Abbas et al 2013; Han et al 2013), new skeletons, sterhirsutins, with cytotoxic and immunosuppressant activities from Stereum hirsutum (Qi et al 2014, 2015), anthraquinone derivatives, with antitumour activities, from an Alternaria species (Chen et al 2014), sarcoviolins, with antioxidative and α‑glucosidase inhibitory activities, from Sarcodon leucopus (Ma et al 2014a), Gloeophyllins A–J, as cytotoxic ergosteroids, from Gloeophyllum abietinum (Han et al 2015). Therefore, fungi from Tibetan Plateau represent an important fungal resource for the discovery of novel chemical molecules.…”

Triterpenoids

“…40 Gloeophyllins A 114-J 123 form an interesting group of normal and rearranged cytotoxic lanostanes from the Tibetan fungus Gloeophyllum abietinum. 41 The structures of compounds 114, 115 and 122 were conrmed by X-ray analyses. Gloeophyllin B 115 has also been isolated from Gloeophyllum odoratum, together with the related compound 124.…”