Penicianstinoids F-K, six undescribed meroterpenoids from the marine algicolous fungus Penicillium sp. RR-DL-1-7.

Six previously undescribed meroterpenoids, penicianstinoids F-K (1-6), together with four known analogues, dehydroaustinol (7), dehydroaustin (8), penicianstinoid A (9), and furanoaustinol (10), were isolated from the cultures of the algicolous fungus Penicillium sp. RR-DL-1-7, derived from the red alga Rhodomela confervoides. Their structures and relative configuration were established by detailed spectroscopic analysis of NMR and HR-MS experiments, and the absolute configurations were assigned by X-ray diffraction and ECD spectral analysis. None of the isolates showed obvious growth inhibitory effects against five plankton and four bacteria species tested.

Lipids and Terpenoids from the Deep-Sea Fungus Trichoderma lixii R22 and Their Antagonism against Two Wheat Pathogens.

Five new lipids, tricholixins A-E (1-5), and two known terpenoids, brasilane A (6) and harzianone A (7), were discovered from a deep-sea strain (R22) of the fungus Trichoderma lixii isolated from the cold seep sediments of the South China Sea. Their structures and relative configurations were identified by meticulous analysis of MS and IR as well as NMR data. The absolute configuration of 5 was ascertained by dimolybdenum-induced ECD data in particular. Compounds 1 and 2 represent the only two new butenolides from marine-derived Trichoderma, and they further add to the structural diversity of these molecules. Although 6 has been reported from a basidiomycete previously, it is the first brasilane aminoglycoside of Trichoderma origin. During the assay against wheat-pathogenic fungi, both 1 and 2 inhibited Fusarium graminearum with an MIC value of 25.0 µg/mL, and 6 suppressed Gaeumannomyces graminis with an MIC value of 12.5 µg/mL. Moreover, the three isolates also showed low toxicity to the brine shrimp Artemia salina.

New ophiobolin sesterterpenoid and drimane sesquiterpenoids from a marine-alga-derived fungus Aspergillus sp.

Further investigation of secondary metabolites of a marine-alga-derived fungus Aspergillus sp. RR-YLW-12 led to isolate one new ophiobolin-type sesterterpenoid (1), four new drimane-type sesquiterpenoids (2-5) and one natural occurring compound (6), together with seven known compounds (7-13). Their structures and stereochemistry were elucidated by extensive spectroscopic analysis of NMR and HRMS experiments, and by comparison with the literature data. All isolates were evaluated for growth inhibition of five marine harmful microalgae. The new compounds exhibited significant to moderate inhibitory effects towards all tested microalgae species with IC50 values ranging from 5.8 to 54.5 µg/mL.

Myrochromanol analogues and trichothecene derivatives from the shellfish-derived fungus Albifimbriaverrucaria.

Eight myrochromanol analogues, including three pairs of epimers at C-2 with the myrochromanol scaffold and two examples of myrochromanol with sugar moiety linked at C-4, together with twelve trichothecene derivatives were isolated from the cultures of a shellfish-derived fungus Albifimbria verrucaria CD1-4. Among them, eight compounds named 2-epi-myrochromanol, ent-myrochromanol B, 4-epi-myrochromanol B, 2-epi-myrochromanol A, myrochromanosides A and B, 6',7'-erythro-(2'E,4'Z)-trichoverrol B, 3R,8S-dihyroxyroridin H were previously undescribed fungal metabolites. Their planar structures and relative configurations were established by 1D and 2D NMR, and HR-MS data analysis, and their absolute configurations were determined using the modified Mosher's method and electronic circular dichrosim calculations. Almost all isolates were evaluated for growth rate inhibition of three marine harmful microalgae Chattonella marina, Heterosigma akashiwo, and Prorocentrum donghaiense, and lethal activity to one marine zooplankton, Artemia salina. Myrochromanosides A and B exhibited obvious inhibitory against three tested microalgae with IC50 values in the range of 9.2-108.9 µM. 8α-Hydroxyroridin H, roridin A and verrucarin A exhibited significant inhibition against P. donghaiense with IC50 values of 6.1, 5.8, and 6.0 µM and toxicity against brine shrimp larvae with LC50 values of 1.4, 2.8, and 0.26 µM, respectively.

Alterbutenolide, a new butenolide derivative from a sponge-derived fungus Alternaria alternata I-YLW6-1.

Alterbutenolide (1), a new butenolide derivative with a long-chain aliphatic acid substitution, together with seven known phenolic compounds i.e. alternariol (2), asperigillol B (3), p-hydroxyphenylacetic acid (4), p-hydroxyphenylethyl alcohol (5), methyl p-hydroxyphenyl acetate (6), 2-(4-hydroxyphenyl)ethyl acetate (7), and 5,6-dihydro-4-methyl-2H-pyran-2-one (8), was isolated from the cultures of a sponge-derived fungus Alternaria alternata I-YLW6-1. The structure of 1 was established on the basis of HR-MS, 1D and 2D NMR, as well as by comparison of the optical rotation data with the literature reported. Compounds 2 and 3 showed significant to moderate inhibitory activities against three harmful microalgae with IC50 values from 3.0 to 36.2 µg/mL, whereas compound 1 only displayed moderate inhibition against Chattonella marina with IC50 value of 34.6 µg/mL. Meanwhile, compounds 3 and 4 showed weak toxicity against brine shrimp larvae with LC50 values >100 µg/mL.

A new lanostane-type triterpenoid from the marine shellfish symbiotic fungus Ceriporia lacerata CD7-5.

One new lanostane-type triterpenoid, 3ß-acetoxy-7,11-dioxolanosta-8,24-dien-21-oic acid (1), together with six known analogues (2-7), were isolated from the cultures of a marine fungus Ceriporia lacerata CD7-5, which was derived from the shellfish Ostrea denselamellosa. Their structures were determined by detailed analysis of spectroscopic data and comparison with the literature reported. The biological activities of these lanostane triterpenoids against marine-derived microalgae, zooplankton, and pathogenic bacteria were also evaluated in this study.

Terpenoids from the Marine-Derived Fungus Aspergillus sp. RR-YLW-12, Associated with the Red Alga Rhodomela confervoides.

Two new meroterpenoids, aspermeroterpenes D and E (1 and 2), two new ophiobolin-type sesterterpenoids, the C-18 epimers of 18,19-dihydro-18-methoxy-19-hydroxyophiobolin P (6 and 7), and two new drimane-type sesquiterpenoids, 3S-hydroxystrobilactone A (8) and 6-epi-strobilactone A (9), along with 11 known terpenoids (3-5 and 10-17) were isolated from the cultures of the algicolous fungus Aspergillus sp. RR-YLW-12, derived from the red alga Rhodomela confervoides. The structures and relative configurations of new compounds were established by detailed spectroscopic analysis of NMR and HRMS experiments, and the absolute configurations were assigned by X-ray diffraction experiments and comparison of their experimental and calculated ECD spectra. Compound 1 features a rare 6/6/6/6/5 pentacyclic system with a meroterpenoid skeleton, and the structure of terretonin E (3) was revised in this study. Compound 4 showed significant inhibitory activities against three microalgae, Prorocentrum donghaiense, Heterosigma akashiwo, and Chattonella marina, with IC50 values of 10.5, 5.2, and 3.1 µg/mL, respectively.

Phenylhydrazone and Quinazoline Derivatives from the Cold-Seep-Derived Fungus Penicillium oxalicum.

Three new phenylhydrazones, penoxahydrazones A-C (compounds 1-3), and two new quinazolines, penoxazolones A (compound 4) and B (compound 5), with unique linkages were isolated from the fungus Penicillium oxalicum obtained from the deep sea cold seep. Their structures and relative configurations were assigned by analysis of 1D/2D NMR and mass spectroscopic data, and the absolute configurations of 1, 4, and 5 were established on the basis of X-ray crystallography or ECD calculations. Compound 1 represents the first natural phenylhydrazone-bearing steroid, while compounds 2 and 3 are rarely occurring phenylhydrazone tautomers. Compounds 4 and 5 are enantiomers that feature quinazoline and cinnamic acid units. Some isolates exhibited inhibition of several marine phytoplankton species and marine-derived bacteria.

Trichobisabolins A-H, eight new bisabolane derivatives from the marine-alga-epiphytic fungus Trichoderma asperellum Y6-2.

Eight new bisabolane derivatives, trichobisabolins A-H, along with two known ones, (3R,6R,7R)-1,10-bisaboladien-3-ol (9) and (3R,6R,7S)-1,10-bisaboladien-3,6-diol (10) were isolated from the culture of Trichoderma asperellum Y6-2, obtained from the surface of the marine red alga Chondrus ocellatus. Their structures and relative configurations were identified by interpretation of 1D/2D NMR and MS data. Compounds 1-8 were assayed for inhibiting the growth of some marine-derived organisms, including four marine phytoplankton species, one marine zooplankton species, and five pathogenic bacteria. All of them exhibited inhibition against the marine phytoplanktons with IC50 values ranging from 2.1-78 µg/mL, compounds 4 and 8 showed weak lethality to the marine zooplankton, and none of them had inhibition against the five pathogenic bacteria.

Two new sesquiterpenoids from the marine-sediment-derived fungus Trichoderma harzianum P1-4.

Three cyclonerane sesquiterpenoids, including the known cyclonerodiol (1), together with its new derivatives, (10E)-12-acetoxy-10-cycloneren-3,7 -diol (2) and 12-acetoxycycloneran-3,7-diol (3) were isolated from the cultures of marine-sediment-derived fungus Trichoderma harzianum P1-4. The structures of the new compounds (2 and 3) were elucidated based on extensive spectroscopic methods (1D/2D NMR and HR-MS) and optical rotation analysis.

Diterpenes and Sesquiterpenes from the Marine Algicolous Fungus Trichoderma harzianum X-5.

Six new terpenes, including one harziane diterpene, 3 R-hydroxy-9 R,10 R-dihydroharzianone (1), one proharziane diterpene, 11 R-methoxy-5,9,13-proharzitrien-3-ol (2), three cyclonerane sesquiterpenes, 11-methoxy-9-cycloneren-3,7-diol (3), 10-cycloneren-3,5,7-triol (4), and methyl 3,7-dihydroxy-15-cycloneranate (5), and one acorane sesquiterpene, 8-acoren-3,11-diol (6), were isolated from the culture of Trichoderma harzianum X-5, an endophytic fungus obtained from the marine brown alga Laminaria japonica. Their structures and relative configurations were established by analysis of 1D/2D NMR, HREIMS, and IR data, and the absolute configurations were assigned on the basis of ECD curves or biogenetic considerations. These terpenes possess four different carbon skeletons, and compound 2, with a rarely occurring bicyclic framework, represents a possible precursor of tetracyclic harzianes. Compounds 1-6 exhibited growth inhibition of some marine phytoplankton species.

Tricholumin A, a Highly Transformed Ergosterol Derivative from the Alga-Endophytic Fungus Trichoderma asperellum.

Tricholumin A (1) with an unprecedented carbon skeleton was isolated from the fungus Trichoderma asperellum cf44-2, an endophyte from the marine brown alga Sargassum sp. Its structure and relative configuration were identified by extensive 1D/2D NMR and mass spectrometric data, and the absolute configuration was assigned by X-ray diffraction and ECD calculations. Compound 1 represents a highly transformed ergosterol derivative, and it exhibited inhibition of some pathogenic microbes and marine phytoplankton species.

Trichocarotins A-H and trichocadinin A, nine sesquiterpenes from the marine-alga-epiphytic fungus Trichoderma virens.

In addition to CAF-603, 14-hydroxy CAF-603 (trichocarane B), 7-ß-hydroxy CAF-603, and trichocarane A, eight new carotane sesquiterpenes, trichocarotins A-H, and one new cadinane sesquiterpene, trichocadinin A, were isolated from the culture of Trichoderma virens Y13-3, obtained from the surface of a marine red alga. Their structures and relative configurations were unambiguously assigned by interpretation of 1D/2D NMR and MS data, and their absolute configurations were established by X-ray diffraction or ECD spectra aided by quantum chemical calculations. These compounds represent two rarely occurring sesquiterpene types from filamentous fungi, and six of them feature potent inhibition against some marine plankton species.

Halogenated and Nonhalogenated Metabolites from the Marine-Alga-Endophytic Fungus Trichoderma asperellum cf44-2.

One new bisabolane sesquiterpene, bisabolan-1,10,11-triol (1), one new norbisabolane sesquiterpene, 12-nor-11-acetoxybisabolen-3,6,7-triol (2), two new naturally occurring monoterpenes, (7S)- and (7R)-1-hydroxy-3-p-menthen-9-oic acids (3 and 4), one new naturally occurring trichodenone, dechlorotrichodenone C (5), one new chlorine-containing trichodenone, 3-hydroxytrichodenone C (6), one new diketopiperazine, methylcordysinin A (7), and one new naturally occurring oxazole derivative, 4-oxazolepropanoic acid (8), were isolated from the culture of a marine brown alga-endophytic strain (cf44-2) of Trichoderma asperellum. Their structures and relative configurations were determined by extensive 1D/2D NMR and mass spectrometric data, and the absolute configurations of 3⁻6 were assigned by analysis of the ECD spectra aided by quantum chemical computations. Compounds 1, 2, 5, and 6 showed growth inhibition of some marine phytoplankton species and pathogenic bacteria.

Bisabolane, cyclonerane, and harziane derivatives from the marine-alga-endophytic fungus Trichoderma asperellum cf44-2.

Three undescribed bisabolane derivatives, trichaspin, trichaspsides A and B, three undescribed cyclonerane sesquiterpenes, 9-cycloneren-3,7,11-triol, 11-cycloneren-3,7,10-triol, and 7,10-epoxycycloneran-3,11,12-triol, and one undescribed harziane diterpene, 11-hydroxy-9-harzien-3-one, were obtained from the culture of Trichoderma asperellum cf44-2, an endophyte of the marine brown alga Sargassum sp. Their structures and relative configurations were assigned by analysis of 1D/2D NMR and MS data, and their absolute configurations were established by ECD or specific optical rotation data. Trichaspin features an unprecedented ethylated bisabolane skeleton, while trichaspsides A and B represent the first aminoglycosides of bisabolane and norbisabolane sesquiterpenes, respectively. Nine of the compounds were evaluated for inhibition of five marine-derived pathogenic bacteria and toxicity to a marine zooplankton.

Trichorenins A-C, Algicidal Tetracyclic Metabolites from the Marine-Alga-Epiphytic Fungus Trichoderma virens Y13-3.

Three novel polyketide-like metabolites, trichorenins A-C (1-3), with a unique tetracyclic carbon skeleton were obtained from the culture of Trichoderma virens Y13-3, an epiphyte of the marine red alga Gracilaria vermiculophylla. Their structures and relative configurations were established by analysis of 1D/2D NMR and MS data, and their absolute configurations were unequivocally assigned by X-ray diffraction and ECD spectra aided by quantum chemical calculations. Compounds 1-3 exhibited potent inhibition against two marine phytoplankton species, Chattonella marina and Karlodinium veneficum.

Two new tricycloalternarene esters from an alga-epiphytic isolate of Alternaria alternata.

Two new tricycloalternarene-type meroterpenes, 17-O-methyltricycloalternarene D (1) and methyl nortricycloalternarate (4), and two known congeners, TCA D (2) and TCA 1b (3), were isolated from the culture of a marine red alga-epiphytic fungal strain (k21-1) of Alternaria alternata. The planar structures and relative configurations of these two new compounds were unequivocally identified by a combination of 1D/2D NMR, UV, IR, and mass spectra and by comparison with literature data, and the absolute configurations were assigned by analysis of ECD spectra. Compounds 1-4 were evaluated for growth inhibition of four marine plankton species, but they appeared weak or moderate to inhibit them.

Hymerhabdrin A, a novel diterpenoid with antifouling activity from the intertidal sponge Hymerhabdia sp.

Hymerhabdrin A (1), a diterpenoid possessing a novel 6/6/5 fused-ring skeleton, together with four known sterols were isolated from an intertidal marine sponge Hymerhabdia sp. Their structures were elucidated by extensive spectroscopic methods, and the relative and absolute configurations of 1 were determined by NOESY analysis and electronic circular dichrosim calculations, respectively. Hymerhabdrin A (1) exhibited significant antifouling activity against Balanus amphitrite larval with LC50 (lethal concentration 50) value of 3.6 µg ml-1.

Sesteralterin and Tricycloalterfurenes A-D: Terpenes with Rarely Occurring Frameworks from the Marine-Alga-Epiphytic Fungus Alternaria alternata k21-1.

A new sesterterpene, sesteralterin (1), four new meroterpenes, tricycloalterfurenes A-D (2-5), and a known meroterpene, TCA-F (6), were obtained from the culture extract of an Alternaria alternata strain (k21-1) isolated from the surface of the marine red alga Lomentaria hakodatensis. The structures and relative/absolute configurations of these compounds were identified by spectroscopic analyses, mainly including 1D/2D NMR, ECD, and mass spectra and quantum chemical calculations. Compound 1 represents the first nitidasane sesterterpene naturally produced by fungi, and 2-5 feature a tetrahydrofuran unit rarely occurring in tricycloalternarenes. Compounds 1-6 were assayed for inhibition of the growth of four marine plankton and one marine alga-pathogenic bacterium.