: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Classification of Aspergillus, Penicillium, Talaromyces and related genera (Eurotiales): An overview of families, genera, subgenera, sections, series and species

Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Xanthones from fungi, lichens, and bacteria : the natural products and their synthesis

Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity and wide variety of biological activities. The strategies to greatly extend natural product scaffolds through available biological and chemical approaches offer unique opportunities to access a new series of natural product analogues, enabling the construction of diverse natural product-like libraries. The affordability of these structurally diverse molecules has been a crucial step in accelerating drug discovery. This review provides an overview of various approaches to exploit the diversity of compounds for natural product-based drug development, drawing upon a series of examples to illustrate each strategy.

Strategies to diversify natural products for drug discovery.

The screening and testing of extracts against a variety of pharmacological targets in order to benefit from the immense natural chemical diversity is a concern in many laboratories worldwide. And several successes have been recorded in finding new actives in natural products, some of which have become new drugs or new sources of inspiration for drugs. But in view of the vast amount of research on the subject, it is surprising that not more drug candidates were found. In our view, it is fundamental to reflect upon the approaches of such drug discovery programs and the technical processes that are used, along with their inherent difficulties and biases. Based on an extensive survey of recent publications, we discuss the origin and the variety of natural chemical diversity as well as the strategies to having the potential to embrace this diversity. It seemed to us that some of the difficulties of the area could be related with the technical approaches that are used, so the present review begins with synthetizing some of the more used discovery strategies, exemplifying some key points, in order to address some of their limitations. It appears that one of the challenges of natural product-based drug discovery programs should be an easier access to renewable sources of plant-derived products. Maximizing the use of the data together with the exploration of chemical diversity while working on reasonable supply of natural product-based entities could be a way to answer this challenge. We suggested alternative ways to access and explore part of this chemical diversity with in vitro cultures. We also reinforced how important it was organizing and making available this worldwide knowledge in an "inventory" of natural products and their sources. And finally, we focused on strategies based on synthetic biology and syntheses that allow reaching industrial scale supply. Approaches based on the opportunities lying in untapped natural plant chemical diversity are also considered.

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

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.

Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus

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.

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

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 calcula...

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

Thirty-one isolates belonging to eight genera in seven orders were identified from 141 strains that were isolated from several marine plants. Alternaria sp. and Fusarium sp. were found to be the predominant fungi. Evaluation of the anti-phytopathogenic bacterial and fungal activities, as well as the cytotoxicity of these 31 extracts, revealed that most of them displayed different levels of bioactivities. Due to their interesting bioactivities, two fungal strains—Fusarium equiseti (P18) and Alternaria sp. (P8)—were selected for chemical investigation and compounds 1–4 were obtained. The structure of 1 was elucidated by 1D and 2D NMR analysis, as well as high-resolution electrospray ionization mass spectroscopy (HRESIMS), and the absolute configuration of its stereogenic carbon (C-11) was established by comparison of the experimental and calculated electronic circular-dichroism (ECD) spectra. Moreover, alterperylenol (4) exhibited antibacterial activity against Clavibacter michiganensis with a minimum inhibitory concentration (MIC) of 1.95 μg/mL, which was 2-fold stronger than that of streptomycin sulfate. Additionally, an antibacterial mechanism study revealed that 4 caused membrane hyperpolarization without evidence of destruction of cell membrane integrity. Furthermore, stemphyperylenol (3) displayed potent antifungal activity against Pestallozzia theae and Alternaria brassicicola with MIC values equal to those of carbendazim. The cytotoxicity of 1 and 2 against human lung carcinoma (A-549), human cervical carcinoma (HeLa), and human hepatoma (HepG2) cell lines were also evaluated.

https://www.mdpi.com/1660-3397/16/1/36/pdf

Anti-Phytopathogenic and Cytotoxic Activities of Crude Extracts and Secondary Metabolites of Marine-Derived Fungi

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).

https://www.mdpi.com/1660-3397/16/9/312/pdf

Fei Cao

Papers

Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus

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

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

Anti-Phytopathogenic and Cytotoxic Activities of Crude Extracts and Secondary Metabolites of Marine-Derived Fungi

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