Rhodium-Catalyzed Hydrolytic Cleavage of the Silicon-Carbon Bond of Silacyclobutanes to Access Silanols.

Herein, we report the first rhodium-catalyzed hydrolytic cleavage of the silicon-carbon bond in silacyclobutanes using water as the reactant. A series of silacyclobutanes could be employed in this reaction in the presence of the Rh/BINAP complex, resulting in the corresponding silanols in good yields. Additionally, a chiral 1,1,4,4-tetraaryl-2,3-O-isopropylidene-l-threitol-derived phosphoramidite ligand could be used in this reaction to yield Si-stereogenic silanol with promising enantioselectivity.

Marine fungal metabolites as a source of drug leads against aquatic pathogens.

Aquatic pathogens, including Vibrio, Edwardsiella, Pseudomonas, and Aeromonas, which could result in bacterial diseases to aquaculture, have seriously threatened the world aquaculture production. Marine-derived fungi, which could produce novel secondary metabolites with significant antibacterial activity, may be an important source for finding effective agents against aquatic pathogens. In this review, a systematically overview of the harm of several aquatic pathogens, and 134 antibacterial secondary metabolites against aquatic pathogens from 13 genera of marine-derived fungi, were summarized and concluded. The aim of this review is to find out the relationships between activity and structural type, between bioactive compounds and their hosts, and so on. Altogether, 95 references published during 1997-2021 were cited. KEY POINTS: •Aquatic pathogens, which could result in bacterial diseases to aquaculture, were described. •Marine fungal metabolites with activities against aquatic pathogens were summarized. •The distributions of these bioactive marine fungal metabolites were analyzed.

Marine-derived fungi as a source of bioactive indole alkaloids with diversified structures.

Marine-derived fungi are well known as rich sources of bioactive natural products. Growing evidences indicated that indole alkaloids, isolated from a variety of marine-derived fungi, have attracted considerable attention for their diverse, challenging structural complexity and promising bioactivities, and therefore, indole alkaloids have potential to be pharmaceutical lead compounds. Systemic compilation of the relevant literature. In this review, we demonstrated a comprehensive overview of 431 new indole alkaloids from 21 genera of marine-derived fungi with an emphasis on their structures and bioactivities, covering literatures published during 1982-2019.

A new epimer of azaphilone derivative pinophilin B from the gorgonian-derived fungus Aspergillus fumigatus 14-27.

A new epimer of azaphilone derivative pinophilin B, epi-pinophilin B (1), and three known analogues (2-4) were obtained from the culture of the gorgonian-derived fungus Aspergillus fumigatus 14-27. The structures of 1-4, including their relative configurations were determined by extensive spectroscopic analysis and comparing with literature data. The absolute configuration of 1 was determined by electronic circular dichroism (ECD) and optical rotatory (OR) calculations methods. Compounds 1-4 were isolated from A. fumigatus for the first time. Their antibacterial and cytotoxic activities were also evaluated.

Marine Natural Products as a Source of Drug Leads against Respiratory Viruses: Structural and Bioactive Diversity.

Respiratory viruses, including influenza virus, respiratory syncytial virus, coronavirus, etc., have seriously threatened the human health. For example, the outbreak of severe acute respiratory syndrome coronavirus, SARS, affected a large number of countries around the world. Marine organisms, which could produce secondary metabolites with novel structures and abundant biological activities, are an important source for seeking effective drugs against respiratory viruses. This report reviews marine natural products with activities against respiratory viruses, the emphasis of which was put on structures and antiviral activities of these natural products. This review has described 167 marinederived secondary metabolites with activities against respiratory viruses published from 1981 to 2019. Altogether 102 references are cited in this review article.

Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum.

Three new quinazoline-containing diketopiperazines, polonimides A-C (1-3), along with four analogues (4-7), were obtained from the marine-derived fungus Penicillium polonicum. Among them, 2 and 4, 3 and 5 were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of 1-3 were determined by 1D nuclear overhauser effect (NOE), Marfey and electron circular dichroism (ECD) methods. Nuclear magnetic resonance (NMR) calculation with the combination of DP4plus probability method was used to distinguish the absolute configurations of C-3 in 3 and 5. All of 1-7 were tested for their chitinase inhibitory activity against OfHex1 and OfChi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds 1-7 exhibited weak activity towards OfHex1 and strong activity towards OfChi-h at a concentration of 10.0 µM, with the inhibition rates of 0.7%-10.3% and 79.1%-95.4%, respectively. Interestingly, 1-7 showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery.

Dipleosporalones A and B, Dimeric Azaphilones from a Marine-Derived Pleosporales sp. Fungus.

Dipleosporalones A and B (1 and 2), two new [2 + 2] azaphilone dimers, were obtained from a marine-derived Pleosporales sp. fungus. The absolute configurations of 1 and 2 were elucidated by calculations of their ECD spectra. Dipleosporalone A (1) possessed an unprecedented skeleton with an uncommon 6/4/6 ring system. Compounds 1 and 2 showed cytotoxicity about 30-90-fold more potent than that of their monomer pinophilin B.

Unusual η1 -Coordinated Alkyne and Alkene Complexes.

This mechanistic study demonstrates that an unusual η1 -coordinated alkyne complex is critical for the 1-pentyne 1,1-diboration reaction. The comparative studies suggest the "pull-push" antagonistic effect arising from Lewis acidity and steric congestion as the reason for the existence of η1 -coordinated alkyne complexes. Analogous η1 -coordinated alkene complexes are also predicted and seem to be promising for their application to the important olefin polymerization reaction.

Asperienes A-D, Bioactive Sesquiterpenes from the Marine-Derived Fungus Aspergillus flavus.

Marine-derived fungi of the genera Aspergillus could produce novel compounds with significant bioactivities. Among these fungi, the strain Aspergillus flavus is notorious for its mutagenic mycotoxins production. However, some minor components with certain toxicities from A. flavus have not been specifically surveyed and might have potent biological activities. Our investigation of the marine-derived fungus Aspergillus flavus CF13-11 cultured in solid medium led to the isolation of four C-6'/C-7' epimeric drimane sesquiterpene esters, asperienes A-D (1-4). Their absolute configurations were assigned by electronic circular dichroism (ECD) and Snatzke's methods. This is the first time that two pairs of C-6'/C-7' epimeric drimane sesquiterpene esters have successfully been separated. Aperienes A-D (1-4) displayed potent bioactivities towards four cell lines with the IC50 values ranging from 1.4 to 8.3 µM. Interestingly, compounds 1 and 4 exhibited lower toxicities than 2 and 3 toward normal GES-1 cells, indicating more potential for development as an antitumor agent in the future.

Discovery of Bioactive Indole-Diketopiperazines from the Marine-Derived Fungus Penicillium brasilianum Aided by Genomic Information.

Identification and analysis of the whole genome of the marine-derived fungus Penicillium brasilianum HBU-136 revealed the presence of an interesting biosynthetic gene cluster (BGC) for non-ribosomal peptide synthetases (NRPS), highly homologous to the BGCs of indole-diketopiperazine derivatives. With the aid of genomic analysis, eight indole-diketopiperazines (1-8), including three new compounds, spirotryprostatin G (1), and cyclotryprostatins F and G (2 and 3), were obtained by large-scale cultivation of the fungal strain HBU-136 using rice medium with 1.0% MgCl2. The absolute configurations of 1-3 were determined by comparison of their experimental electronic circular dichroism (ECD) with calculated ECD spectra. Selective cytotoxicities were observed for compounds 1 and 4 against HL-60 cell line with the IC50 values of 6.0 and 7.9 µM, respectively, whereas 2, 3, and 5 against MCF-7 cell line with the IC50 values of 7.6, 10.8, and 5.1 µM, respectively.

Anti-Vibrio Indole-Diterpenoids and C-25 Epimeric Steroids From the Marine-Derived Fungus Penicillium janthinellum.

A systematic chemical exploration of the marine-derived fungus Penicillium janthinellum led to the isolation of four indole-diterpenoid derivatives (1-4), including new penijanthines C and D (1 and 2), and a pair of new steroidal epimers, penijanthoids A and B (5 and 6). The calculated ECD spectra and Snatzke's method for the new compound 1 were carried out to determine its absolute configuration. The absolute configuration of 3 was established by X-ray diffraction and calculated ECD methods for the first time. DP4plus approach was used to elucidate the absolute configurations of the C-25 epimeric steroids 5 and 6. 25-Epimeric 5 and 6 represent the first examples of steroids forming a five-membered lactone between C-23 and C-27 from marine fungi. Compounds 1, 2, 5, and 6 displayed significant anti-Vibrio activity (Minimum inhibitory concentration, MIC values ranging from 3.1 to 50.0 µM) against three pathogenic Vibrio spp.

Absolute Configuration of Bioactive Azaphilones from the Marine-Derived Fungus Pleosporales sp. CF09-1.

Investigation of the marine-derived fungus Pleosporales sp. CF09-1 cultured in modified PDB medium led to the isolation of six new azaphilone derivatives, pleosporalones B and C (1 and 2) and pleosporalones E-H (4-7), and one known analogue (3). The absolute configurations of C-2' and C-3' in 3 were assigned by a vibrational circular dichroism method. The C-11 relative configurations for the pair of C-11 epimers (4 and 5) were established by comparing the magnitude of the computed 13C NMR chemical shifts (Δδcalcd) with the experimental 13C NMR values (Δδexp) for the epimers. Antiphytopathogenic and anti- Vibrio activities were evaluated for 1-7. Pleosporalone B (1) exhibited potent antifungal activities against the fungi Alternaria brassicicola and Fusarium oxysporum with the same MIC value of 1.6 µg/mL, which were stronger than the positive control ketoconazole among these compounds. Additionally, pleosporalone C (2) displayed significant activity against the fungus Botryosphaeria dothidea (MIC, 3.1 µg/mL). Compounds 6 and 7 displayed moderate anti- Vibrio activities against Vibrio anguillarum and Vibrio parahemolyticus, with MIC values of 13 and 6.3 µg/mL for 6 and 6.3 and 25 µg/mL for 7, respectively.

The absolute configuration of anti-Vibrio citrinin dimeric derivative by VCD, ECD and NMR methods.

Citrinin dimeric derivatives are bioactive polyketides previously reported from Penicillium, Aspergillus and Monascus fungi species. Due to the large distance between the stereogenic centers of the two monomer units, it was difficult to determine the absolute configuration of the whole molecule (1). In previous work, the absolute configuration of 1 was just proposed by biogenetic considerations. To address this problem, the experimental VCD of 1 was compared with the corresponding DFT calculations for two diastereomers (1a and 1b). Also, the experimental ECD and NMR spectra of 1 were combined for analysis with the corresponding theoretical predictions for different diastereomers. Additionally, compound 1 showed promising anti-Vibrio activity against pathogenic Vibrio spp. with MIC values ranging from 0.4 to 0.8 µM.

Four new antitumor metabolites isolated from a mutant 3-f-31 strain derived from Penicillium purpurogenum G59.

Penicimutanolones A (1) and B (2), penicimutanolone A methyl ether (3), and penicimumide (4), four new antitumor metabolites, were isolated from a neomycin-resistant mutant of the marine-derived fungus Penicillium purpurogenum G59. The structures of the compounds were elucidated by spectroscopic methods, and the absolute configurations were determined by X-ray crystallography and calculated ECD. In MTT and SRB assays, compounds 1-3 showed strong inhibitory effects on 14 human cancer cell lines. Compounds 1 and 2 maybe induce apoptosis of cancer cells mainly due to the inhibition of the expression of survivin, a client protein of HSP90. In addition, in vivo antitumor activity was observed for compound 1 in murine sarcoma HCT116 tumor-bearing Kunming mice, using docetaxel as a positive control.

Aspergixanthones I⁻K, New Anti-Vibrio Prenylxanthones from the Marine-Derived Fungus Aspergillus sp. ZA-01.

Marine-derived fungi are a rich source of structurally diverse metabolites. Fungi produce an array of compounds when grown under different cultivation conditions. In the present work, different media were used to cultivate the fungus Aspergillus sp. ZA-01, which was previously studied for the production of bioactive compounds, and three new prenylxanthone derivatives, aspergixanthones I⁻K (1⁻3), and four known analogues (4⁻7) were obtained. The absolute configuration of 1 was assigned by ECD experiment and the Mo2(AcO)4 ICD spectrum of its methanolysis derivative (1a). All the compounds (1⁻7) were evaluated for their anti-Vibrio activities. Aspergixanthone I (1) showed the strongest anti-Vibrio activity against Vibrio parahemolyticus (MIC = 1.56 µM), Vibrio anguillarum (MIC = 1.56 µM), and Vibrio alginolyticus (MIC = 3.12 µM).

Absolute Configurations of 14,15-Hydroxylated Prenylxanthones from a Marine-Derived Aspergillus sp. Fungus by Chiroptical Methods.

Determination of the absolute configrations for natural products is one of the most important and challenging tasks, especially when the molecules display high conformational flexibility. In this paper, eight new prenylxanthones, aspergixanthones A-H (1-8), and one known analogue (9), were isolated from the marine-derived fungus Aspergillus sp. ZA-01. The absolute configurations of C-14 and C-15 in 1-8 were difficult to be assigned due to the high conformational flexibility of the chains. To solve this problem, the experimental ECD, ORD, and VCD spectra of 1 were combined for analysis with the corresponding theoretical predictions for its different diastereomers. This study suggested that a concerted application of more than one chiroptical methods could be used as a preferable approach for the stereochemical characterizations of flexible molecules. Compounds 1-9 were evaluated for their cytotoxic and antibacterial activities. Among them, 6 showed cytotoxicity against the A-549 cell line with the IC50 value of 1.1 µM, and 7 exhibited antibacterial activity against Micrococcus lysodeikticus with the MIC value of 0.78 µg/mL.

A pair of enantiomeric 5-oxabicyclic[4.3.0]lactam derivatives and one new polyketide from the marine-derived fungus Penicillium griseofulvum.

A pair of enantiomeric 4-oxabicyclic[4.3.0]lactam derivatives, (+)- and (-)-penicilactam A (1), and one new polyketide derivative penicitrinone F (2) were isolated from the marine-derived fungus Penicillium griseofulvum GT-10. Their structures and absolute configurations were elucidated through extensive spectroscopic analyses combined with the calculated ECD spectra. Penicitrinone F (2) had moderate inhibitory activity towards Bacillus subtilis with a MIC value of 6.3 µM.

Cytotoxic Serrulatane-Type Diterpenoids from the Gorgonian Euplexaura sp. and Their Absolute Configurations by Vibrational Circular Dichroism.

Vibrational circular dichroism (VCD) method has become robust and reliable alternative for the stereochemical characterization of natural products. In this paper, three new serrulatane-type diterpenoids, euplexaurenes A-C (1-3), and a known metabolite, anthogorgiene P (4), were obtained from the South China Sea gorgonian Euplexaura sp. GXWZ-05. The absolute configuration of C-11 in 1-4, which was difficult to be determined by common means due to the high conformational flexibility of the eight-carbon aliphatic chain attached at C-4, was determined by VCD method, suggesting a new horizon to define the absolute configurations of natural products possessing chains. Compounds 1-4 were found to show selective cytotoxic activities against human laryngeal carcinoma (Hep-2) cell line with the IC50 values of 1.95, 7.80, 13.6 and 5.85 µM, respectively.

Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus.

Six new azaphilone derivatives, talaraculones A-F (1-6), together with five known analogues (7-11), were obtained from the saline soil-derived fungus Talaromyces aculeatus. The absolute configurations of 1 and 6 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compounds 1 and 5 represent the first reported azaphilone derivatives with a C4 aliphatic side chain and a methylal group at C-3, respectively. Talaraculones A and B (1 and 2) exhibited stronger inhibitory activity against α-glucosidase than the positive control acarbose (IC50 = 101.5 µM), with IC50 values of 78.6 and 22.9 µM, respectively.