Isolation and characterization of three pairs of verrucosidin epimers from the marine sediment‑derived fungus Penicillium cyclopium and confguration revision of penicyrone A and related analogues

Verrucosidins,a methylatedα-pyrone class of polyketides rarely reported upon,have been implicated in one or more neurological diseases.Despite the signifcance of verrucosidins as neurotoxins,the absolute confgurations of most of the derivatives have not been accurately characterized yet.In this study,three pairs of C-9 epimeric verrucosidin derivatives,including the known compounds penicyrones A and B(1a/1b)and 9-O-methylpenicyrones A and B(2a/2b),the new compounds 9-O-ethylpenicyrones A and B(3a/3b),together with the related known derivative verrucosidin(4),were isolated and identifed from the culture extract of Penicillium cyclopium SD-413,which was obtained from the marine sediment collected from the East China sea.Their structures were established based on an in-depth analysis of nuclear magnetic resonances(NMR)and mass spectroscopic data.Determination of the absolute confgurations of these compounds was accomplished by Mosher’s method and time-dependent density functional theory(TDDFT)calculations of electronic circular dichroism(ECD)and optical rotation(OR).The confgurational assignment of penicyrone A demonstrated that the previously reported C-6 absolute confguration of verrucosidin derivatives needs to be revised from(6S)to(6R).The 9R/9S epimers of compounds 1–3 were found to exhibit growth inhibition against some pathogenic bacteria,indicating that they have potential as lead compounds for the creation of antimicrobial agents.

Uncommon N-Methoxyindolediketopiperazines from Acrostalagmus luteoalbus,a Marine Algal Isolate of Endophytic Fungus

Main observation and conclusion Four new N-methoxyindolediketopiperazines(acrozines D—G,1—4)and six known congeners(5—10)were purified from the organic extract of Acrostalagmus luteoalbus TK-43,which was a marine algal-derived fungus obtained from Codium fragile.Their structures were determined by interpretation of NMR and mass spectroscopic data.The structures of compounds 1,2,and 4 including their absolute configurations were confirmed by single-crystal X-ray diffraction,while the absolute configuration of compound 3 was elucidated by comparative analysis of ECD and TDDFT-ECD calculations.Compounds 1—4,with a unique methoxy substitution at N-2,were rarely discovered among indolediketopiperazine alkaloids.All these compounds were evaluated for antimicrobial activities against human-and aquatic-pathogenic bacteria and plant-related pathogenic fungi,with compounds 5 and 7 exhibiting potent activity against Edwardsiella icataluri(MIC=3 and 5μmol/L,respectively),while compound 9 displayed a broad spectrum of antibacterial activities.The four new compounds were further tested for anti-acetylcholinesterase(AChE)properties,and compound 3 exhibited inhibitory activity with IC_(50)value of 8.4μmol/L.

Polyoxygenated dihydropyrano[2,3-c]pyrrole-4,5-dione derivatives from the marine mangrove-derived endophytic fungus Penicillium brocae MA-231 and their antimicrobial activity

A new polyoxygenated dihydropyrano[2,3-c]pyrrole-4,5-dione derivative, pyranonigrin F （1）, together with a related known compound, pyranonigrin A （2）, were isolated and identified from Penicillium brocae MA-231, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these metabolites were determined based on comprehensive spectral interpretation and the absolute configuration of compound 1 was established by X-ray crystallographic analysis. Compounds 1 and 2 showed potent activity against a broad spectrum of human-, aqua-, and plant-pathogens.

Prenylated indole alkaloids from the marine-derived fungus Paecilomyces variotii

Two new prenylated indole alkaloids,namely,dihydrocarneamide A（1） and iso-notoamide B（2）,were isolated from the marine-derived endophytic fungus Paecilomyces variotii EN-291.The structures of these metabolites were determined based on comprehensive spectral analysis,together with chiral HPLC analysis of the acidic hydrolysates.Unlike other prenylated indole alkaloids such as asperparalines,notoamides,and versicolamides,compounds 1 and 2 are the rare examples of C-5 prenylation,forming the fused dimethyldihydropyran ring at C-5 and C-6 of the indole ring.The cytotoxic activity of the isolated compounds was evaluated.

Mycochemistry of marine algicolous fungi

Marine algicolous fungi refer to the fungi inhabiting or associated with marine algae,which have attracted a great attention for natural product researchers due to their chemical diversity and biological activity during the past two decades.Up to the end of 2014,a total of 366 new natural products,including polyketides,terpenoids,polyketide-terpenoids,peptides,alkaloids,and shikimate derivatives,have been characterized from them.Among these metabolites,240 compounds feature cytotoxic,antibacterial,antifungal,antimicroalgal,zooplankton-toxic,antiprotozoal,antioxidative,enzyme-modulatory,and/or some other activities.This review gives a comprehensive coverage of both chemical and biological aspects of the secondary metabolites from marine algicolous fungi.

Chemical diversity and biological function of indolediketopiperazines from marine-derived fungi

Natural products from marine-derived fungi have attracted considerable attention in the recent two decades.Indolediketopiperazines are one of the most important classes of marine natural products,mainly discovered from the fungal genera Penicillium,Aspergillus and Eurotium.These compounds span a wide range of chemical structures and bioactivities.This review summarizes 155 indolediketopiperazines that were discovered from marine-derived fungi from 2000 to early 2019 and primarily focuses on their chemical diversity and biological function.

Experimental and Computational Analysis of the Solution and Solid-State Conformations of Hexadepsipeptides from Beauveria felina

Chemical investigation of Beouverio felina,a marine-derived entomopathogenic fungus,obtained two new destruxin hexadepsipeptides(1 and 2)containing an/.-Ala^(5)residue instead of the usual A/-Me-L-Ala^(5).Interestingly,the presence of the/.-Ala^(5)residue enabled two slowly-exchanging solution conformers with cis/trons(ILE^(3))-(A/-Me-Val^(4))amide bond for 1 and 2 with 1.5:1 and 1:1 cis/trans ratios,respectively,while only the conformer with c/s amide bond was found in the solid-state.The solution and solid-state conformers were studied by NMR,X-ray diffraction and solution and solid-state ECD measurements,as well as by TDDFT-ECD calculations.Structural(conformational)parameter-activity correlations suggested that the extended destruxin geometry with the preferred c/s(ILE^(3))-(A/-Me-Val^(4))bond probably resulted in improved bioactivity and reduced toxicity for the destruxin class.This was the first report on the interconversion phenomenon of cis/trans amide bonds of destruxin class,which could give insights in the development of bioactive destruxin agents with lower toxicity.