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Ergosterol is an essential component for fungi, including entomopathogenic fungi like Cordyceps. Cordyceps has been used as a traditional medicine in Japan and China and possesses various unique ergostane-type sterols, those exhibit bioactivities. In this manuscript, we reported the isolation of 2 new ergostane-type sterols, 1 and 2 along with ten sterols (3-12) from 7 strains of Cordyceps related fungal strains, Cordyceps takaomontana NBRC 101754, Metarhizium owariense NBRC 33258, Polycephalomyces formosus NBRC 109994, Cordyceps tuberculata NBRC 106948, Cordyceps tenuipes NBRC 108997, Cordyceps sp. NBRC 106954, and Tolypocladium paradoxum NBRC 106958 collected fruiting bodies of Ophiocordyceps heteropoda. In addition, the antitrypanosomal activity and antimicrobial activity of isolates were tested to find 6 showed the antitrypanosomal activity, and the minimum inhibitory concentration (MIC) value was confirmed as 1.41 µg/mL. In the antimicrobial assay, the MIC value of 8 against methicillin-resistant Staphylococcus aureus was determined to be 3.1 µg/mL.

The ortho-tyrosinol derivative, as a key synthetic intermediate for alkaloidal metabolites of Cordyceps, was synthesized from L-phenylalanine methyl ester via condensation with crotonic acid and oxidative intramolecular lactone formation by using phenyliodine(III) bis(trifluoroacetate). Subsequent elongation of the side chain involving a cross-metathesis reaction and deprotection yielded cordytakaoamide B and cordycepamide C in notably few synthetic steps. Furthermore, the S-configurations at the C-2 position of both cordytakaoamide B and cordycepamide C were confirmed by comparison with the sign of the optical rotation of the synthetic sample.

Three known polyol menthane monoterpenoids, namely, (4 R)-1- p-menthen-6,8-diol (1), (4 R)-1- p-menthen-4,7-diol (2), and (1 R,2 R,4 R)- p-menthane-1,2,4-triol (3), and 6 known phenolics (4-9), in addition to β-sitosterol 3- O-glucoside (10), were isolated from the aerial parts of Daucus carota subsp. hispidus (Ball) Heywood (Family: Apiaceae) growing in Tunisia. The structures of the isolated compounds were established depending upon the spectroscopic techniques including one and two-dimensional nuclear magnetic resonance (1D, and 2D NMR) and high resolution mass spectroscopy (HRMS). The absolute configuration of the compounds 1 to 3 was determined using experimental circular dichroism (CD) for the first time. Compounds 1 to 3 were reported for the first time from this plant. Compounds 1 to 3 exhibited no antimicrobial and antioxidant activity using superoxide dismutase-like activities. Compounds 2 and 3 exhibited weak activity, while 1 showed negative cytotoxic activity against human mouth squamous carcinoma (HSC-2) and human cervical cells (HeLa) cancer cells.

A new diphenyl ether glycoside, xylosmaloside (1), was isolated from the MeOH extract of Xylosma longifolium Clos. The structure of xylosmaloside (1) was elucidated using MS analyses, extensive 2D-homo and heteronuclear NMR data interpretation and the chemical conversions. Xylosmaloside (1) showed stronger antioxidant activity than ascorbic acid.

During the search for bioactive secondary metabolites, thelepalmatins A and B (1 and 2) were isolated from the fresh fruiting bodies of Thelephora palmata, together with four known compounds (3-6). Their structures were elucidated using MS analyses, and extensive 2D-heteronuclear NMR data interpretation. Compounds 3, 4 and 6 showed antimicrobial activities against Staphylococcus aureus and Bacillus subtilis with MIC values of 21.7-70.4 μM.

During the search for secondary metabolites with antiproliferative activity, six new lanostane triterpenoids, tyrosamic acids A-F (1–6) together with ten known compounds (7–16), were isolated from the fruiting body of Tyromyces sambuceus. Their structures were elucidated using MS analyses, extensive 2D-heteronuclear NMR data interpretation and the structure of 3 was further confirmed by single-crystal X-ray data analyses. All lanostane triterpenoids (1–16) possesses a carboxy group at C-20 position and their strength of antiproliferative activity was affected by the presence or absence of a hydroxy group at C-15 position and at the side chain. Four of the compounds (1, 6, 10, 14) showed antiproliferative activities against human cancer cell lines with IC50 values of 16.8–48.3 μM (HL-60).

To obtain the structural diversity of bioactive compounds similar to cotylenins and fusicoccins that modulate 14-3-3 protein-protein interactions in eukaryotes, screening tests were carried out using the lettuce seed dormancy breaking-assay. An acetone extract of the liverwort Plagiochila sciophila exhibited significant activity against the seeds in the presence of the plant hormone abscisic acid. Activity-guided fractionation of the extract afforded the isolation of seven novel fusicoccane-type diterpenoids, named fusicosciophins A-E (1–5), 8-deacetyl (6) and 9-deacetyl fusicosciophin E (7). Their structures were determined by spectroscopic methods and X-ray crystallographic analyses. All the pure isolated compounds (1–7) exhibited moderate lettuce seed dormancy breaking activity. In addition, the differentiation-inducing activity and cytotoxicity of these isolates, together with fusicoccin A (FC-A) and all- trans retinoic acid (ATRA), were evaluated in human promyelocytic leukemia HL-60 cells and human mouth epidermal carcinoma KB cells, respectively. Fusicosciophins (2 and 4) and FC-A exhibited moderate differentiation-inducing activity (EC50 31.2~59.1μM) compared with ATRA (EC50 0.3μM), while 2, 4 and ATRA exhibited higher selectivity indices (IC50/EC50 >3.38~667) than FC-A (IC50/EC50 1.05). This is the first report on the isolation of fusicoccane-type diterpenoids from liverworts having seed dormancy breaking activity and differentiation-inducing activity in mammal cells.