Jinwei Ren

Stucturally Diverse Sesquiterpenes Produced by a Chinese Tibet Fungus Stereum hirsutum and Their Cytotoxic and Immunosuppressant Activities

Two new heterodimeric sesquiterpenes, sterhirsutins C (1) and D (2), along with eight new sesquiterpenoid derivatives, sterhirsutins E--L (3-10), were isolated from the culture of Stereum hirsutum. The absolute configuration of 1 was assigned by a single-crystal X-ray diffraction experiment. Compounds 1 and 2 possessed an unprecedented chemical skeleton with a 5/5/5/6/9/4 fused ring system. Compound 10 is the first sesquiterpene coupled with a xanthine moiety. Compounds 1-10 showed cytotoxicity against K562 and HCT116 cell lines. Compound 9 induced autophagy in HeLa cells. Compound 5 inhibited the activation of IFNβ promoter in Sendai virus infected cells.

Sterhirsutins A and B, Two New Heterodimeric Sesquiterpenes with a New Skeleton from the Culture of Stereum hirsutum Collected in Tibet Plateau

Two new heterodimeric sesquiterpenes, sterhirsutins A (1) and B (2), and two new sesquiterpenes, hirsutic acids D-E (3 and 4), were identified from the culture of Stereum hirsutum. The absolute configurations in 1 and 2 were confirmed by single-crystal X-ray diffraction experiments and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are likely biosynthesized from a hirsutane-type sesquiterpene and α-humulene by a hetero-Diels-Alder cycloaddition. Compounds 1-4 showed cytotoxicity against K562 and HCT116 cell lines.

Versicoamides F–H, Prenylated Indole Alkaloids from Aspergillus tennesseensis

Three highly modified indole alkaloids, versicoamides F-H (1-3), together with seven known alkaloids (4-10) were isolated from the fungus Aspergillus tennesseensis. The structures of new compounds were determined by analysis of the NMR and MS spectroscopic data. The absolute configurations of 1 and 2 were assigned by single-crystal X-ray diffraction experiments. Compounds 1 and 2 showed weak antiproliferative activity against the H460 cell line. Compounds 1-3 represent a new class of natural product hybrids with new chemical skeletons.

Ganoboninketals A-C, Antiplasmodial 3,4-seco-27-Norlanostane Triterpenes from Ganoderma boninense Pat.

Three new nortriterpenes, ganoboninketals A-C (1-3), featuring rearranged 3,4-seco-27-norlanostane skeletons and highly complex polycyclic systems were isolated from the medicinal mushroom Ganoderma boninense. The structures of the new metabolites were established by spectroscopic methods. The absolute configurations in 1-3 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1-3 showed antiplasmodial activity against Plasmodium falciparum with IC50 values of 4.0, 7.9, and 1.7 μM, respectively. Compounds 1 and 3 also displayed weak cytotoxicity against A549 cell line with IC50 values of 47.6 and 35.8 μM, respectively. Compound 2 showed weak cytotoxicity toward HeLa cell line with an IC50 value of 65.5 μM. Compounds 1-3 also presented NO inhibitory activity in the LPS-induced macrophages with IC50 values of 98.3, 24.3, and 60.9 μM, respectively.

Discovery and Characterization of a New Family of Diterpene Cyclases in Bacteria and Fungi

Diterpene cyclases from bacteria and basidiomycete fungi are seldom studied. Here, we presented the identification and verification of EriG, a member of the UbiA superfamily, as the enzyme responsible for the cyclization of the cyathane skeleton in the mushroom Hericium erinaceum. Genome mining using the EriG protein sequence as a probe led to the discovery of a new family of ubiquitous UbiA-related diterpene cyclases in bacteria and fungi. We successfully characterized seven new diterpene cyclases from bacteria or basidiomycete fungi with the help of an engineered Escherichia coli strain and determined the structures of their corresponding products. A new diterpene with an unusual skeleton was generated during this process. The discovery of this new family of diterpene cyclases provides new insight into the UbiA superfamily.

Identification of Oxaphenalenone Ketals from the Ascomycete Fungus Neonectria sp.

Neonectrolides B-E (4-7), four new oxaphenalenone ketals incorporating the new furo[2,3-b]isochromeno[3,4,5-def]chromen-11(6aH)-one skeleton, were isolated from the fermentation extract of the ascomycete fungus Neonectria sp. in an in-depth investigation guided by HPLC fingerprint and a cytotoxicity assay. The previously identified oxaphenalenone spiroketal neonectrolide A (1) and its putative biosynthetic precursors (2 and 3) were also reisolated in the current work. The structures of 4-7 were primarily elucidated by interpretation of NMR spectroscopic data, and the absolute configurations were deduced by electronic circular dichroism calculations. Compound 6 showed cytotoxic effects against four of the six human tumor cell lines tested. Biosynthetically, compounds 4-7 could be derived via the Diels-Alder reaction cascades starting from derivatives of the co-isolated metabolites 2 and 3.

Asperorydines A–M: Prenylated Tryptophan-Derived Alkaloids with Neurotrophic Effects from Aspergillus oryzae

As part of our program to discover new bioactive agents from fungi, 13 new alkaloids accompanying 13 known related alkaloids were isolated from a wild strain of Aspergillus oryzae L1020. Compounds 1 and 2 have unprecedented 6/6/5/7/5 and 6/6/6/5/5 chemical skeletons, representing new members of quinoline alkaloids. Compound 3 is a new macrolactam with an unusual 6/5/6/8 ring system. Compounds 4-13 are new α-cyclopiazonic acid-related alkaloids. The absolute configurations of 1-4, 8, and 9 were assigned by electronic circular dichroism calculations. Compounds 2, 5, 6, 11, 14, 22, and 26 exhibit pronounced neurite outgrowth-promoting effects on PC12 cells in the range of 25-100 μM.

Correction to Versicoamides F–H, Prenylated Indole Alkaloids from Aspergillus tennesseensis

of compounds Versicoamides F−H (1−3), notoamide O (7), notoamide Q (8), and dehydronotoamide E (9) are incorrect and should be Versicolamides F−H (1−3), notoamide Q (7), dehydronotoamide C (8), and 17-epi-notoamide Q (9), respectively. The reference to 17-epi-notoamide Q (9) (Nat. Chem. 2009, 1, 63−68) should be replaced with the reference shown below. The authors apologize to the scientific community for the inconvenience caused by these errors.

New 1, 2-naphthoquinone-derived pigments from the mycobiont of lichen Trypethelium eluteriae Sprengel

Abstract A new yellow pigment trypethelonamide A (1), and a new dark violet-red pigment 5′-hydroxytrypethelone (2), as well as three known dark violet-red pigments (+)-8-hydroxy-7-methoxytrypethelone (3), (+)-trypethelone (4) and (-)-trypethelone (5) were isolated from the cultured lichenized fungus Trypethelium eluteriae. The structures of 1 and 2 were determined to be 1, 2-naphthoquinone derivatives by extensive spectroscopic analysis. The absolute configurations of 1 and 2 were assigned by quantum electronic circular dichroism (ECD) calculation. All isolated compounds were evaluated for cytotoxicities against A549, HepG2 and RKO cell lines, and antioxidant effects on DPPH. Compounds 1–5 showed moderate and weak cytotoxicities against RKO cell line with IC50 from 22.6 to 113.5 μM.

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

ABSTRACT Two new secondary metabolites, kongiilines A and B (1, 7), and two asperphenamate derivatives, asperphenamates B and C (5–6), together with 16 known compounds (2–4, 8–20), were isolated from Tibetan Plateau fungi Penicillium kongii and Penicillium brasilianum. This is the first report on asperphenamates B and C as naturally occurring compounds, and that aspterric acid is isolated from P. brasilianum for the first time. Their structures were elucidated by different spectroscopic techniques including high-resolution electrospray ionisation mass spectrum, 1D nuclear magnetic resonance (NMR), and 2D NMR as well as electronic circular dichroism. Compounds 4, 5, and 10 exhibited cytotoxicity activities against human colon carcinoma HCT116 cell line with IC50 values of 88.16, 77.68, and 36.92 μM, respectively. Fungi from Tibetan Plateau represent important and rich resources for the investigation of new chemicals.