Cytotoxic Cleistanthane and Cassane Diterpenoids from the Entomogenous Fungus Paraconiothyrium hawaiiense

Abstract

Hawaiinolides A-D (1-4), four new secondary metabolites including three cleistanthane (1, 3, and 4) and one cassane (2) type of diterpene lactones, were isolated from the crude extract of Paraconiothyrium hawaiiense, a fungus entomogenous to the Septobasidium-infected insect Diaspidiotus sp. The structures of 1-4 were elucidated by nuclear magnetic resonance experiments, and 1 and 3 were further confirmed by X-ray crystallography. The absolute configuration of 1 was assigned via single-crystal X-ray diffraction analysis using Cu Kα radiation, whereas that of 2-4 was deduced via the circular dichroism data. Compound 1 showed significant cytotoxicity against a small panel of five human tumor cell lines, A549, T24, HeLa, HCT116, and MCF-7.

Hypocriols A–F, Heterodimeric Botryane Ethers from Hypocrea sp., an Insect-Associated Fungus

“…The absolute configurations for C-16, C-26, and C-24 were deduced by comparison of the experimental CD spectrum of 4 with the simulated ECD spectra for the 16S,24S,26R (4Aa) and 16R,24R,26S (4Ab) enantiomers of the simplified structure 4A (Figures 5 and S41). 4,6,7,8,9,12 59.0, CH 1.75,d (10.9) 1,3,4,6,7,8,9,12 58.8,CH 1.82,d (10.5) 1,4,6,7,8,9,12 6 46 . 5,6,8,12,13,14,15 49.9,CH 2 2.19,d (11.2) 5,6,8,12,13,14,15 7b 1.15,d (11.6) 5,6,8,9,13,14 1.07,d (10.3) 5, 6, 8, 9, 13, 14 1...…”

“…Full-scan spectra were acquired over a scan range of m/z 100−1000 at 1.03 spectra/s. HPLC separations were performed on an 1.40,dd (11.1,2.9) 2,8,9,10,11 2 34.7,CH 1.77,m 1,3,4,10,11 3a 40.8, CH 2 1.83,ddd (12.2,3.4,3.4) 1,2,4,5,11 3b 1.12,dd (12.2,10.7) 1,2,4,5,11 4 73.4,CH 5.12,ddd (11.0,10.7,3.4) 2,3,5,6,31 5 58.8,CH 1.80,d (11.0) 3,4,6,7,8,9,12,13 6 46.6, qC 7a 50.4, CH 2 2.30, d (11.5) 6, 8, 12, 13, 14, 15 7b 1.24, d (11.5) 5, 6, 8, 9, 13, 14, 15 8 58 . The isolate was identified based on morphology and sequence (GenBank accession no. KF724627) analysis of the ITS region of the rDNA.…”

“…The fraction (5.6 g) eluted with 100:1 CH 2 Cl 2 −MeOH was separated by silica gel CC using petroleum ether−EtOAc gradient Table 3. NMR Data for 5 and 6 (Acetone-d 6 ) 5 6 CH 1.59,d (12.5) 2,3,8,9,10,11 56.1,CH 1.61,d (12.4) 2,3,8,9,10,11 2 29.9, CH 1. 2, 4, 5, 11 4 73.0, CH 5.07, ddd (11.1,11.0,4.8) 5,6,31 73.0,CH 5.07,ddd (11.1,11.0,4.7) 5,6,31 5 60.5,CH 1.84,d (10.9) 3,4,6,7,8,9,12 61.0,CH 1.86,d (11.0) 4,6,8,9,12,13 6 39.4,qC 39.4,qC 7a 51.0, CH 2 1.80, d (11.5) 5, 6, 8, 12, 13, 14, 15 51.0, CH …”

“…2, 4, 5, 11 4 73.0, CH 5.07, ddd (11.1,11.0,4.8) 5,6,31 73.0,CH 5.07,ddd (11.1,11.0,4.7) 5,6,31 5 60.5,CH 1.84,d (10.9) 3,4,6,7,8,9,12 61.0,CH 1.86,d (11.0) 4,6,8,9,12,13 6 39.4,qC 39.4,qC 7a 51.0, CH 2 1.80, d (11.5) 5, 6, 8, 12, 13, 14, 15 51.0, CH 2 1.85, d (11.6) 6, 8, 9, 12, 13, 14, 15 7b 1.07, d (11.5) 5, 6, 8, 9, 13, 14 1.11, d (11.6) 5, 6, 8, 9, 12, 13, 14 8 46 . 3. 12, d (12.2) 8, 9, 10, 14 3.28, d (10.2) 8, 9, 10, 14 16a 58 . 21, 22, 24, 25, 26, 28, 29, 30 23b 1.82, d (13.2) 21, 22, 24, 25, 26, 28, 29, 30 1.71, d (13.1) 21, 22, 24, 25, 26, 29, 30 24 49 . 1,4,5,9 3.79,s 1,5,…”

Secondary metabolites from the marine‐derived fungus Paraconiothyrium sp. VK‐13

“…Marine-derived fungi are considered as a rich source of novel and bioactive metabolites, of which many lead compounds have been found for drug discovery and development. The fungi of the genus Paraconiothyrium have been shown to produce diverse classes of secondary metabolites, including sesquiterpenoids, [1][2][3] diterpenoids, [4,5] isoprenoid decalins, [6,7] furanones, [8,9] polyketides, [10] and dihydrocoumarins. [11] Some compounds have been reported to possess cytotoxicity [1,3,7] and antibacterial activities [2,9] .…”