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Fungal metabolites (1–8) including known compounds, TMC-264 (1), PR-toxin (6) and a sesquiterpene (7), and new natural products 2–5 and 8, were isolated from the mangrove endophytic fungus Penicillium chermesinum. Compound 2 was a novel tetracyclic polyketide uniquely spiro-attached with a γ-lactone ring. Compounds 1 and 6 exhibited comparable cytotoxic activity to that of doxorubicin, and they selectively exhibited activity toward certain cancer cell lines. The cytotoxicity of 1 might be due to the β-chloro substituted α,β-unsaturated ketone functionality, which was reactive toward glutathione and peptides containing a thiol group. The polyketide 1 reacted with glutathione and peptides under physiological conditions, and its thiol-reactive pharmacophore is possibly applicable to the design of glutathione modulation agents, fragment-based drug discovery (for irreversible enzyme inhibitors), bioconjugation, and click reactions. Facile C–S bond formation in water (catalyst-free conditions) inspired by 1 could also be useful for green chemistry.

A new concept of catalysts which are prepared from renewable materials is demonstrated. It is known that amino acids (e.g., proline and hydroxyproline) are robust organocatalysts for several reactions. Bovine tendons which are proteins rich in hydroxyproline and proline were used as a source of amino acids. An acid hydrolysate of tendons (a TH catalyst) could catalyze two reactions: (i) the synthesis of coumarins and chromenes under solvent-free conditions and (ii) the synthesis of densely functionalized 4H-chromenes via a three-component reaction. Moreover, an economical and easily accessible TH catalyst is applicable in a multigram scale synthesis of coumarins and chromenes, as well as in the three-component reaction for chromene synthesis. A catalytic activity of hydroxyproline for the synthesis of 4H-chromenes via the three-component reaction was also discovered. The present work demonstrates not only the green catalysts from renewable materials, but also an environmentally benign preparation of coumarins and chromenes.

Directed biosynthesis through biohalogenation of depsidones was conducted by cultivating the marine-derived fungus Aspergillus unguis in media containing different halogen salts (i.e., KBr, KI, and KF). The fungus grown in a KBr medium produced new brominated unnatural natural depsidones, while those cultured in KI produced non-halogenated depsidone, unguinol, as a major metabolite. Unexpectedly, the directed biosynthesis through biohalogenation provides insights into depsidone biosynthesis; particular biosynthetic intermediates were co-isolated with brominated depsidones from the fungus cultured in KBr medium. These biosynthetic congeners support that the depsidone biosynthesis in A. unguis operates through the oxidative coupling of depsides, not through the benzophenone-grisadienedione pathway. The isolated depsidones inhibited aromatase, a therapeutic target for the treatment of breast cancer.

Structurally unique isocoumarin glucosides, named halorosellins A (1) and B (2), were isolated from the EtOAc extract of a broth of the marine fungus Halorosellinia oceanica. Other new minor metabolites including 4,8-dihydroxy-6-methoxy-4,5-dimethyl-3-methyleneisochroman-1-one (3), 3-acetyl-7-hydroxy-5-methoxy-3,4-dimethyl-3H-isobenzofuran-1-one (4) and an ophiobolane sesterterpene, 17-dehydroxyhalorosellinic acid (5), were also isolated. Structures of these compounds were elucidated by analyses of spectroscopic data. Compound 4 exhibited mild antimycobacterial activity (MIC value of 200 µg mL−1).

Flavans from the roots of Desmos cochinchinensis exhibited potent aromatase inhibitory activity at nanomolar levels, and could be leads for the development of anti-aromatase drugs. In addition, these aromatase inhibitors did not show pronounced cytotoxic activity. Flavans exert their inhibitory activity through binding, as revealed by molecular docking studies, with aromatase at Arg115, Met374, and Leu477; the C-7 hydroxyl (or methoxyl) forms hydrogen bonds with Met374 and Arg115 of aromatase.