Cylindromicin from Arctic-Derived Fungus Tolypocladium sp. SCSIO 40433

The fungus strain SCSIO 40433 was isolated from an Arctic-derived glacier sediment sample and characterized as Tolypocladium cylindrosporum. A new compound, cylindromicin (1), and seven known secondary metabolites (2–8) were isolated from this strain. The chemical structures of these compounds were elucidated by comprehensive spectroscopic analyses. Cylindromicin (1) featured a 3,4-dihydro-2H-pyran skeleton. The absolute configuration of compound 1 was assigned via interpretation of key Nuclear Overhauser Effect Spectroscopy (NOESY) correlations and Electronic Circular Dichroism (ECD) calculation. Cylindromicin (1) exhibited significant tyrosinase inhibition activity. This study highlights Polar fungi as a potential resource for new bioactive natural products.     

Zizaane-Type Sesquiterpenoids and Their Rearranged Derivatives from Agarwood of an Aquilaria Plant

Nine new sesquiterpenoids (1–9) were isolated from ethyl ether extract of agarwood originated from Aquilaria sp., including three novel sesquiterpenoids (1–3) derived from zizaane, together with six zizaane-type sesquiterpenoids (4–9). All structures were unambiguously elucidated based on 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of sesquiterpenoids was determined by comparison of the experimental and computed ECD spectra. In vitro anti-inflammatory assessment showed that compound 9 exhibited inhibition of NO production in LPS-stimulated RAW264.7 cells with an IC₅₀ value of 62.22 ± 1.27 μM.     

Optimization of crystal packing in semiconducting spin-crossover materials with fractionally charged TCNQδ− anions (0 < δ < 1)

Co-crystallization of the prominent Fe(ii) spin-crossover (SCO) cation, [Fe(3-bpp)₂]²⁺ (3-bpp = 2,6-bis(pyrazol-3-yl)pyridine), with a fractionally charged TCNQ^δ− radical anion has afforded a hybrid complex [Fe(3-bpp)₂](TCNQ)₃·5MeCN (1·5MeCN, where δ = −0.67). The partially desolvated material shows semiconducting behavior, with the room temperature conductivity σ_RT = 3.1 × 10⁻³ S cm⁻¹, and weak modulation of conducting properties in the region of the spin transition. The complete desolvation, however, results in the loss of hysteretic behavior and a very gradual SCO that spans the temperature range of 200 K. A related complex with integer-charged TCNQ⁻ anions, [Fe(3-bpp)₂](TCNQ)₂·3MeCN (2·3MeCN), readily loses the interstitial solvent to afford desolvated complex 2 that undergoes an abrupt and hysteretic spin transition centered at 106 K, with an 11 K thermal hysteresis. Complex 2 also exhibits a temperature-induced excited spin-state trapping (TIESST) effect, upon which a metastable high-spin state is trapped by flash-cooling from room temperature to 10 K. Heating above 85 K restores the ground-state low-spin configuration. An approach to improve the structural stability of such complexes is demonstrated by using a related ligand 2,6-bis(benzimidazol-2′-yl)pyridine (bzimpy) to obtain [Fe(bzimpy)₂](TCNQ)₆·2Me₂CO (4) and [Fe(bzimpy)₂](TCNQ)₅·5MeCN (5), both of which exist as LS complexes up to 400 K and exhibit semiconducting behavior, with σ_RT = 9.1 × 10⁻² S cm⁻¹ and 1.8 × 10⁻³ S cm⁻¹, respectively.

Co-crystallization of the cationic complex [Fe(3-bpp)2]²⁺ with fractionally charged TCNQ^δ− anions (0 < δ < 1) affords semiconducting spin-crossover (SCO) materials. The abruptness of SCO is strongly dependent on the interstitial solvent content.     

Chemical Variability and In Vitro Anti-Inflammatory Activity of Leaf Essential Oil from Ivorian Isolona dewevrei (De Wild. & T. Durand) Engl. & Diels

The chemical variability and the in vitro anti-inflammatory activity of the leaf essential oil from Ivorian Isolona dewevrei were investigated for the first time. Forty-seven oil samples were analyzed using a combination of CC, GC(RI), GC-MS and ¹³C-NMR, thus leading to the identification of 113 constituents (90.8–98.9%). As the main components varied drastically from sample to sample, the 47 oil compositions were submitted to hierarchical cluster and principal components analyses. Three distinct groups, each divided into two subgroups, were evidenced. Subgroup I−A was dominated by (Z)-β-ocimene, β-eudesmol, germacrene D and (E)-β-ocimene, while (10βH)-1β,8β-oxido-cadina-4-ene, santalenone, trans-α-bergamotene and trans-β-bergamotene were the main compounds of Subgroup I−B. The prevalent constituents of Subgroup II−A were germacrene B, (E)-β-caryophyllene, (5αH,10βMe)-6,12-oxido-elema-1,3,6,11(12)-tetraene and γ-elemene. Subgroup II−B displayed germacrene B, germacrene D and (Z)-β-ocimene as the majority compounds. Germacrene D was the most abundant constituent of Group III, followed in Subgroup III−A by (E)-β-caryophyllene, (10βH)-1β,8β-oxido-cadina-4-ene, germacrene D-8-one, and then in Subgroup III−B by (Z)-β-ocimene and (E)-β-ocimene. The observed qualitative and quantitative chemical variability was probably due to combined factors, mostly phenology and season, then harvest site to a lesser extent. The lipoxygenase inhibition by a leaf oil sample was also evaluated. The oil IC₅₀ (0.020 ± 0.005 mg/mL) was slightly higher than the non-competitive lipoxygenase inhibitor NDGA IC₅₀ (0.013 ± 0.003 mg/mL), suggesting a significant in vitro anti-inflammatory potential.     

Tröger's base scaffold in racemic and chiral fashion as a spacer for bisdistamycin formation. Synthesis and DNA binding study

‘Head-to-head’ oligo-N-methylpyrrole peptide dimers linked by a methano[1,5]diazocin scaffold are presented in racemic as well as chiral fashion. Their DNA binding activities were assayed on calf thymus DNA, poly(dA-dT)₂, and poly(dC-dG)₂ by NMR and ECD spectroscopies, and fluorescence probe displacement assay. The presented dimers prefer AT sequences, but show higher affinity to poly(dC-dG)₂ than distamycin A. The (4R,9R) configuration of methanodiazocin bridge was found to be better suited for interaction with ct-DNA and poly(dA-dT)₂ than (4S,9S) configuration.     

Two Antimicrobial Heterodimeric Tetrahydroxanthones with a 7,7′-Linkage from Mangrove Endophytic Fungus Aspergillus flavus QQYZ

Mangrove endophytic fungi represent significant and sustainable sources of novel metabolites with unique structures and excellent biological activities, attracting extensive chemical investigations. In this research, two novel heterodimeric tetrahydroxanthones, aflaxanthones A (1) and B (2), dimerized via an unprecedented 7,7′-linkage, a sp³-sp³ dimeric manner, were isolated from the mangrove endophytic fungus Aspergillus flavus QQYZ. Their structures were elucidated through high resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopy, the absolute configurations of them were determined by a single-crystal X-ray diffraction combined with calculated electronic circular dichroism (ECD) spectra and a 1D potential energy scan. These compounds were evaluated for antifungal activities in vitro and exhibited broad-spectrum and potential antifungal activities against several pathogenic fungi with minimum inhibitory concentration (MIC) values in the range of 3.13–50 μM. They also performed moderate antibacterial activities against several bacteria with MIC values in the range of 12.5–25 μM. This research enriched the resources of lead compounds and templates for marine-derived antimicrobial drugs.     

New Natural Oxygenated Sesquiterpenes and Chemical Composition of Leaf Essential Oil from Ivoirian Isolona dewevrei (De Wild. & T. Durand) Engl. & Diels

This study aimed to investigate the chemical composition of the leaf essential oil from Ivoirian Isolona dewevrei. A combination of chromatographic and spectroscopic techniques (GC(RI), GC-MS and ¹³C-NMR) was used to analyze two oil samples (S1 and S2). Detailed analysis by repetitive column chromatography (CC) of essential oil sample S2 was performed, leading to the isolation of four compounds. Their structures were elucidated by QTOF-MS, 1D and 2D-NMR as (10βH)-1β,8β-oxido-cadin-4-ene (38), 4-methylene-(7αH)-germacra-1(10),5-dien-8β-ol (cis-germacrene D-8-ol) (52), 4-methylene-(7αH)-germacra-1(10),5-dien-8α-ol (trans-germacrene D-8-ol) (53) and cadina-1(10),4-dien-8β-ol (56). Compounds 38, 52 and 53 are new, whereas NMR data of 56 are reported for the first time. Lastly, 57 constituents accounting for 95.5% (S1) and 97.1% (S2) of the whole compositions were identified. Samples S1 and S2 were dominated by germacrene D (23.6 and 20.5%, respectively), followed by germacrene D-8-one (8.9 and 8.7%), (10βH)-1β,8β-oxido-cadin-4-ene (7.3 and 8.7), 4-methylene-(7αH)-germacra-1(10),5-dien-8β-ol (7.8 and 7.4%) and cadina-1(10),4-dien-8β-ol (7.6 and 7.2%). Leaves from I. dewevrei produced sesquiterpene-rich essential oil with an original chemical composition, involving various compounds reported for the first time among the main components. Integrated analysis by GC(RI), GC-MS and ¹³C-NMR appeared fruitful for the knowledge of such a complex essential oil.     

Asymmetric Synthesis of Tetrahydroisoquinoline Derivatives through 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with Allyl Alkyl Ketones

A [3 + 2] 1,3-Dipolar cycloaddition of C,N-cyclic azomethine imines with allyl alkyl ketones has been achieved. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. An array of tetrahydroisoquinoline derivatives is generally constructed with good diastereoselectivities and enantioselectivities (up to >25:1 dr, >95% ee). Moreover, the absolute configuration of the product was previously determined by using the quantum electronic circular dichroism calculation and ECD spectrum method.     

Absolute configuration of bioactive furanogermacrenones from Commiphora erythraea (Ehrenb) Engl. by computational analysis of their chiroptical properties

Absolute configurations (+)-(4S), (+)-(3S,4R), (−)-(2S,4S), and (−)-(1R,2R,4S) were assigned, for the first time, to bioactive furanogermacranes extracted from Commiphora erythraea resin by DFT computational analysis of their ORD curves and ECD spectra. This analysis established that all of these compounds share the same absolute configuration at the methyl-substituted carbon thus allowing us to hypothesize a biosynthetic relationship among these structurally related metabolites.     

Synthesis of the Natural Product Building Block 5‐(3‐Bromophenyl)‐4‐hydroxy‐5‐methylhexan‐2‐one and its Chiral Characterization by Using Chiroptical Spectroscopy

The absolute configuration of 5‐(3‐bromophenyl)‐4‐hydroxy‐5‐methylhexan‐2‐one, an intermediate in the synthesis of various natural products, is assigned by using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD). Experimental spectra were compared to density functional theory (DFT) calculations of the molecule with known configuration. These three techniques independently confirm that the absolute configuration is (S)‐5‐(3‐bromophenyl)‐4‐hydroxy‐5‐methylhexan‐2‐one, thus enabling us to assign the absolute configuration with high reliability. The reliability of the VCD analysis was assessed quantitatively by using the CompareVOA program. We found that, in cases in which the agreement between theory and experiment was very good, a value of 10 cm^?1 for the triangular weighting function gave a more‐realistic discriminative power between enantiomers than the default value of 20 cm^?1.     

Assignment of Absolute Configurations of Two Promising Anti-Helicobacter pylori Agents from the Marine Sponge-Derived Fungus Aspergillus niger L14

A chemical investigation into endozoic fungus Aspergillus niger L14 derived from the marine sponge of Reniera japonica collected off Xinghai Bay (China) resulted in the isolation of two dimeric naphtho-γ-pyrones, fonsecinone A (1) and isoaurasperone A (2). Through a combination of ECD spectra and X-ray diffraction analysis, the chiral axes of compounds 1 and 2 were unambiguously determined as R_α-configurations. Bioassay results indicated that these substances exhibited remarkably inhibitory effects on human pathogens Helicobacter pylori G27 and 159 with MIC values of ≤4 μg/mL, which are similar to those of the positive control, ampicillin sodium. To the best of our knowledge, this is the first report on absolute configuration of 1 and crystallographic data of 2, as well as their potent anti-H. pylori activities.     

Ochraceopyronide,a Rare α-Pyrone-C-lyxofuranoside from a Soil-Derived Fungus Aspergillus ochraceopetaliformis

The fungal strain was isolated from a soil sample collected in Giza province, Egypt, and was identified as Aspergillus ochraceopetaliformis based on phenotypic and genotypic data. The ethyl acetate extract of the fungal strain exhibited promising activity levels against several pathogenic test organisms and through a series of ¹H NMR guided chromatographic separations, a new α-pyrone-C-lyxofuranoside (1) along with four known compounds (2–5) were isolated. The planar structure of the new metabolite was elucidated by detailed analysis of its 1D/2D NMR and HRMS/IR/UV spectroscopic data, while the relative configuration of the sugar moiety was determined by a combined study of NOESY and coupling constants data, with the aid of theoretical calculations. The structures of the known compounds—isolated for the first time from A. ochraceopetaliformis—were established by comparison of their spectroscopic data with those in the literature. All isolated fungal metabolites were evaluated for their antibacterial and antifungal activities against six Gram-positive and Gram-negative bacteria as well as against three human pathogenic fungi.     

振动圆二色谱在轴手性β-双咔啉N—O衍生物立体化学研究中的应用

采用振动圆二色谱(VCD)方法研究了一个具有高度催化活性的轴手性结构的双咔啉N—O化合物的立体化学结构. 在B3LYP/6-311+G(d)水平上得到的计算结果表明, 对于具有负旋光值的双咔啉N—O化合物化合物, 其绝对构型是aS. 同时, 分别计算了双咔啉N—O化合物的电子圆二色谱(ECD)和旋光值, 并与实验结果进行了比较. 在化合物结构完全正确条件下, VCD, ECD和旋光数据均表明, 具有负旋光值的该化合物的绝对构型是aS.     

Five New Terpenes with Cytotoxic Activity from Pestalotiopsis sp.

Five new compounds called Pestalotis A–E (1–5), comprising three monoterpene-lactone compounds (1–3), one tetrahydrobenzofuran derivative (4), and one sesquiterpene (5), were isolated from the EtOAc extract of Pestalotiopsis sp. The structures of the new compounds were elucidated by analysis of their NMR, HRMS, and ECD spectra, and the absolute configurations were established through the comparison of experimental and calculated ECD spectra. All compounds were tested for antitumor activity against SW-480, LoVo, HuH-7, and MCF-7. The results showed that compounds 2 and 4 exhibited potent antitumor activity against SW-480, LoVo, and HuH-7 cell lines. Furthermore, compound 4 was assessed against HuH-7, and the results indicated that the rate of apoptosis was dose-dependent.     

Chiraloptical properties of adducts derived from cyclic nitrones and 2(5H)-furanones. Combined experimental and theoretical studies

The validity of the Bucourt–Legrand empirical rule, which relates the configuration at the α-carbon atom in the lactone unit with the sign of the lactone n→π^* transition observed in the electronic circular dichroism (ECD) spectrum of 5-5-5 and 5-5-6 fused heterocyclic systems, was investigated. For this purpose, a combination of ECD spectroscopy, time-dependent density functional theory (TD-DFT) and molecular modelling calculations supported additionally by X-ray diffraction analysis, was applied. Model compounds were obtained via the 1,3-dipolar cycloaddition of 2(5H)-furanones and five- and six-membered cyclic nitrones. In addition, cycloadducts either with or without an additional interfering chromophore were selected. A comparison of the recorded ECD spectra with those simulated by the TD-DFT calculations gave a reasonable interpretation of the excitations observed in the 210–230 nm spectroscopic range. Generally, calculations confirmed the validity of the Bucourt–Legrand rule and demonstrated that ECD may be used as a highly sensitive probe for the three-dimensional molecular structure of the systems studied herein. Notable behaviour, however, was observed in the case of some 5-5-6 fused systems substituted with BnO group. In these cases, the conformational liability and coupling of molecular lactone excitation with other chromophores cause a change of orientation of the transition dipole moments resulting in a breakdown of the rule.     

Selectivity over coverage in de novo sequencing of IgGs

Although incredibly diverse in specificity, millions of unique Immunoglobulin G (IgG) molecules in the human antibody repertoire share most of their amino acid sequence. These constant parts of IgG do not yield any useful information in attempts to sequence antibodies de novo. Therefore, methods focusing solely on the variable regions and providing unambiguous sequence reads are strongly advantageous. We report a mass spectrometry-based method that uses electron capture dissociation (ECD) to provide straightforward-to-read sequence ladders for the variable parts of both the light and heavy chains, with a preference for the functionally important CDR3. We optimized this method on the therapeutic antibody Trastuzumab and demonstrate its applicability on two monoclonal quartets of the four IgG subclasses, IgG1, IgG2, IgG3 and IgG4. The method is based on proteolytically separating the variable F(ab′)₂ part from the conserved Fc part, whereafter the F(ab′)₂ portions are mass-analyzed and fragmented by ECD. Pure ECD, without additional collisional activation, leads to straightforward-to-read sequence tags covering the CDR3 of both the light and heavy chains. Using molecular modelling and structural analysis, we discuss and explain this selective fragmentation behavior and describe how structural features of the different IgG subclasses lead to distinct fragmentation patterns. Overall, we foresee that pure ECD on F(ab′)₂ or Fab molecules can become a valuable tool for the de novo sequencing of serum antibodies.     

Bioactive PKS–NRPS Alkaloids from the Plant-Derived Endophytic Fungus Xylaria arbuscula

A novel hybrid PKS–NRPS alkaloid, xylarialoid A (1), containing a 13-membered macrocyclic moiety and [5,5,6] fused tricarbocyclic rings, together with ten known cytochalasins (2–11), was isolated from a plant-derived endophytic fungus, Xylaria arbuscula. The chemical structures of all compounds were elucidated using 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculation. Compounds 1–3 and 10 exhibited significant antitumor activities against A549 and Hep G2 cell lines, with IC₅₀ values of 3.6–19.6 μM. In addition, compound 1 showed potent anti-inflammatory activity against LPS-induced nitric oxide (NO) production in macrophage RAW 264.7 cells (IC₅₀, 6.6 μM).     

Davidones F and G,Two Novel Flavonoids from Sophora davidii (Franch.) Skeels

An unprecedented novel flavanone davidone F (1) with a seven-membered ring side chain, and a novel flavanonol davidone G (2), along with 11 known flavonoids, were isolated from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. Their planar structures were established by UV, IR, HRESIMS, 1D and 2D NMR data. The relative configurations of 1 and 2 were determined by calculation of NMR chemical shift values, the absolute configuration of 1 and 2 were assigned by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Moreover, compounds 1–13 were screened for the translocation activity of glucose transporter 4 (GLUT-4), and the fluorescence intensity was increased to the range of 1.56 and 2.79 folds. Compounds 1 and 2 showed moderate GLUT-4 translocation activity with 1.64 and 1.79 folds enhancement, respectively, at a concentration of 20 μg/mL.     

Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam,Useful Intermediate for the Synthesis of Bioactive Compounds

During the past several years, the frequency of discovery of new molecular entities based on γ- or δ-lactam scaffolds has increased continuously. Most of them are characterized by the presence of at least one chiral center. Herein, we present the preparation, isolation and the absolute configuration assignment of enantiomeric 2-(4-bromophenyl)-1-isobutyl-6-oxopiperidin-3-carboxylic acid (trans-1). For the preparation of racemic trans-1, the Castagnoli-Cushman reaction was employed. (Semi)-preparative enantioselective HPLC allowed to obtain enantiomerically pure trans-1 whose absolute configuration was assigned by X-ray diffractometry. Compound (+)-(2R,3R)-1 represents a reference compound for the configurational study of structurally related lactams.     

(−)-6-epi-Artemisinin,a Natural Stereoisomer of (+)-Artemisinin in the Opposite Enantiomeric Series,from the Endemic Madagascar Plant Saldinia proboscidea,an Atypical Source

Chemical and biological investigation of the Madagascar endemic plant Saldinia proboscidea led to the isolation of an isomer of artemisinin, (−)-6-epi-artemisinin (2). Its structure was elucidated using a combination of NMR and mass spectrometry. The absolute configuration was established by chemical syntheses of compound 2 as well as a new stereoisomer (3). The comparable bioactivities of artemisinin (1) and its isomer (−)-6-epi-artemisinin (2) revealed that this change in configuration was not critical to their biological properties. Bioactivity was assessed using an apoptosis induction assay, a SARS-CoV-2 inhibitor assay, and a haematin polymerization inhibitory activity (HPIA) assay. This is the first report of an artemisinin-related compound from a genus not belonging to Artemisia and it is the first isolation of an artemisinin-related natural product that is the opposite enantiomeric series relative to artemisinin from Artemisia annua.