Optical Rotation Values Research Articles

Effect of Solvent on the Optical Rotation of Azatryptophan Derivatives.

Chirally pure enantiomers of differently protected 7-azatryptophan derivatives (R-3c, S-3c, R-3i, S-3i, R-3m, S-3m, R-3aa, and S-3aa) were synthesized, which showed solvent-dependent optical rotation. The obtained results not only exhibited changes in the values but also showed the variation in sign (- or +) with the different solvents studied. The change in optical rotation value was essentially attributed to the electron-donating property, which can be correlated to the donor number of the solvents. There are two types of hydrogen bonds, intramolecular (i.e., form within the structure) and intermolecular (i.e., form with external groups such as solvents). These hydrogen bonds are responsible for the value and sign variations, and 1H NMR experiments were used to further characterize them. The NMR data suggested that hydrogen bond formation is occurring between the Fmoc NH group vicinal to the chiral center and donor group of the corresponding solvent.

Effect of IONIZING radiation on the stereochemical composition of dihydroquercetin sample

Introduction. Microbiological quality is one of the key criteria for active pharmaceutical ingredients. To ensure it, a set of preventive measures and various decontamination methods are used. A relatively new approach is ionizing radiation, characterized by high efficiency. However, according to the literature, during ionizing sterilization, a change in the chemical composition of the drug may occur, which requires studying the effect of the radiation factor on each individual compound. Objective. To investigate the effect of ionizing radiation on the stereoisomeric composition of the dihydroquercetin (DHQ), a natural flavananol and a promising object for the development of chiral remedies. Material and methods. The object of the study is a sample of DHQ exposed to ionizing radiation of 9.5 MeV (DHQrad), while the reference sample is a native substance of DHQ from the same manufacturer and batch (DHQref). Analysis was conducted using polarimetry and reversed-phase HPLC with diode array and mass spectrometric detection. Results. Taking into account the moisture content of the samples, the average values of the specific optical rotation for acetone solutions of DHQrad and DHQref were 20.85±1.54° and 19.65±1.93°, respectively. Chromatograms showed two peaks with retention times of 10.18±0.03 and 11.63±0.01 min, which, based on UV and mass spectra profiles, were identified as trans- and cis-diastereomers of DHQ. The total content of flavananol in the analyzed samples was 93.25±0.01% for DHQrad and 94.92±0.01% for DHQref, with the amount of the cis-isomer being 0.59±0.13% and 1.27±0.70%, respectively. Conclusion. The study did not establish a significant effect of ionizing radiation on the specific optical rotation value and the stereoisomeric composition of the DHQ substance. The findings support the recommendation of this sterilization method for remedies containing the studied flavananol.

Bioactive Secondary Metabolites Produced by the Hadal Actinomycete Streptomyces sp. SY1414 Isolated from the Mariana Trench-derived Sediment

Background:: Accumulated investigations have demonstrated that the Mariana Trench is enriched in microorganisms. However, the diversity of structures and bioactivities of the secondary metabolites produced by the Mariana Trench-associated microorganisms is poorly known, which needs to be intensively investigated. Objective:: This study aimed to investigate the bioactive secondary metabolites produced by a Mariana Trench-derived actinomycete Streptomyces sp. SY1414 was cultured in BY medium, which was chosen from four different media based on the diversity of secondary metabolites. Methods:: A combination of different column chromatographs and HPLC was applied for the separation and purification of the secondary metabolites. The structures of the isolated compounds were determined mainly based on their NMR data, optical rotation values, and the comparison with the reference data, and the Sulforhodamine B (SRB) method was used to evaluate the anti-glioma activity of isolated compounds. Results:: Four different types of compounds were isolated from the large culture of strain Streptomyces sp. SY1414 in BY medium, including a benzoquinoline alkaloid, actinophenanthroline C (1), a benzamide, (2E,4E)-5-(3-hydroxyphenyl)-penta-2,4-dienamide (2), a cyclopeptide, valinomycin (3), and four macrolides of bafilomycin D (4), bafilomycin A2 (5), bafilomycin W (6), and C(19), C(21)- O-methyl-bafilomycin A1 (7). Actinophenanthroline C (1), bafilomycin D (4), bafilomycin A2 (5), and bafilomycin W (6) displayed significant anti-glioma activities with IC50 values ranging from 1.62 to 8.20 μM for U87MG cells and 2.45 to 3.89 μM for U251. The anti-gliomas of actinophenanthroline C (1) was reported for the first time. Conclusion:: The hadal actinomycete Streptomyces sp. SY1414 in BY medium produced four different types of secondary metabolites with significant anti-glioma activity, which enriched the diversity of structures and bioactivities of the Mariana Trench-associated natural products.

Exploitation of Mechanistic Product Selectivity for the Two‐Step Synthesis of Optically Active Bio‐Derived Cyclic Carbonates Incorporating Amino Acids

AbstractThe synthesis of bio‐derived cyclic carbonates is attracting a lot of attention as the incorporation of bio‐derived functionality into these compounds provides the opportunity to prepare previously unknown structures, whilst also improving their sustainability profiles. This study presents a facile preparation of diastereomerically pure bio‐derived cyclic carbonates displaying a range of optical rotation values. These compounds are obtained from glycidol, amino acids and CO2 in a facile two‐step approach. Initially, the diastereomerically pure amino acid functionalised epoxides are prepared through a robust Steglich esterification of enantiopure glycidol (R or S) and an amino acid (D or L). Thereafter, in a second step, cycloaddition of the epoxide with CO2 results in the retention of the initial stereochemistry of the epoxide, furnishing novel diastereomerically pure and optically active cyclic carbonate products. A DFT study has explained the basis of this observed retention of configuration for these compounds. Further, results from this DFT study also provide new mechanistic information concerning a co‐catalyst‐free cycloaddition reaction starting from glycidol when using the gallium‐catalyst, which is found to operate through metal‐ligand cooperativity.

The combination of ATR-FTIR and chemometrics for discrimination of Red Ginger (Zingiber Officinale Var Rubrum) oil in West Sumatra and its antioxidant activity

Their origin influences the chemical components and pharmacological action of essential oils. This study aimed to classify red ginger oil (RGO) based on its FTIR spectra combined with chemometrics and determine its antioxidant activity. Fresh red ginger rhizomes were collected from six West Sumatra regions and extracted using hydrodistillation. ATR-FTIR and Chemometrics were used to classify the oil, and its antioxidant activity was tested using various methods. The study found that RGO was golden yellow with a unique odor, and it had a yield range of 0.52% - 0.86%, a specific gravity of 0.83-0.94 g/ml, a refractive index of 1.4834 – 1.4880, and an optical rotation value of -36.382. However, all RGO samples had low antioxidant activity. Principal Component Analysis (PCA) showed that RGO can be separated based on the altitude of the growing locations at the wavenumber 2000-400 cm-1. Hierarchical Clustering Analysis (HCA) revealed three clusters of RGO: I; Solok, II; Kamang Magek and Batusangkar, III; Dharmasraya, Pesisir Selatan, and Pasaman Barat, with different FTIR fingerprints. In conclusion, red ginger oil from different parts of West Sumatra has unique metabolite profiling and low antioxidant activity levels.

Three new Furano-lactones from the endophytic fungus Aspergillus nidulans

Three new furano-lactones, asperilactones A−C (1–3), and two known compounds silvaticol (4) and violaceic acid (5) were isolated from an ethanol extract of Aspergillus nidulans, a fungus isolated from the Annelida Whitmania pigra Whitman (Haemopidae). Their structures were elucidated by a combination of spectroscopy, ECD calculations, comparing optical rotation values, and single-crystal X-ray diffraction analyses. Asperilactone A (1) represented the first example of furano-lactone with an unusual 2-thia-6-oxabicyclo[3.3.0]octane ring system. Asperilactones A and B showed weak toxicity against the HL-60 and RKO.

3-Hydroxy-3-(2-oxopropyl)indolin-2-one, a product of a human-derived Enterocloster strain, is an inhibitor of nitric oxide production.

When cultured anaerobically, Enterocloster sp. RD014215 was found to produce 1. Using nuclear magnetic resonance and mass spectroscopy, the planar structure of 1 was determined to be 3-hydroxy-3-(2-oxopropyl)indolin-2-one. The chirality of 1 was implied as S by comparing the optical rotation value of 1 with literature reports of the synthesized compounds. To our knowledge, this work represents the first discovery of the metabolite produced by Enterocloster strain. 1 exhibited inhibition of nitric oxide (NO) production, demonstrating a 50% inhibitory activity (IC50) of 34 µm for NO production by murine macrophage cells subjected to lipopolysaccharide stimulation.

Iridoids from the aerial parts of Adenosma caeruleum with their nitric oxide inhibitory effects

Three new iridoids, adenocaeroids A−C (1−3), and seven known analogs, umbellatolide B (4), pedicularis-lactone (5), iridolactone (6), artselaenin C (7), eucommiol (8), rehmaglutin D (9), and 3-deoxy-artselaenin C (10) were isolated from the aerial parts of Adenosma caeruleum. Their chemical structures were identified by the comprehensive spectroscopic methods, including 1D and 2D NMR and HRESI mass spectra. The relative configurations of 1−3 were established by analyzing their NOESY spectra as well as by DFT-GIAO NMR calculations followed by ML-J-DP4, DP4+, and DU8 methods. The absolute configurations of 1−3 were determined by comparing experimental and calculated ECD spectra and specific optical rotation values. All of the compounds, except 7 and 10, inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 microglial cells in a dose-dependent manner, with IC50 values ranging from 28.4−61.8 µM. However, none of the compounds showed inhibitory effect on protein-tyrosine phosphatase 1B (PTP1B) activity.

Meroterpenoids with divers' rings systems from Phyllosticta capitalensis and their anti-inflammatory activity

Four undescribed sesquiterpene-shikimates (1–4), eight undescribed monoterpene-shikimates (5–12), together with two known ones were isolated and identified from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Capitalensis A (1) was identified as the first sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid degradation product, while capitalensis B (2) is a sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid with a unique D-ring formed by a C-2–O–C-9′ connection. The structures of these previously undescribed compounds were elucidated by multiple techniques, including IR, HR-ESI-MS, and NMR analysis. Furthermore, their absolute configurations were established through the comprehensive approach that involved the calculations of ECD spectra, optical rotation values, and single-crystal X-ray analysis. Moreover, the anti-inflammatory activity of all isolated compounds was evaluated using a lipopolysaccharide (LPS)-induced inflammation model in BV2 microglial cells. Meanwhile, these compounds exhibited activity in inhibiting NO production. Four compounds, capitalensis C (3), capitalensis D (4), 15-hydroxyl tricycloalternarene 5b (13) and guignarenone A (14) showed strong inhibitory effects with IC50 values of 21.6 ± 1.33, 12.2 ± 1.08, 18.6 ± 1.27, and 15.8 ± 1.20 μM, respectively. In addition, the structure-activity relationship of the anti-inflammatory activity of the compounds was discussed.

Alkaloid diversity expansion of a talent fungus Penicillium raistrichii through OSMAC-based cultivation.

Alkaloidal natural products are attractive for their broad spectrum of pharmaceutical bioactivities. In the present work, the highly productive saline soil derived fungus, Penicillium raistrichii, was subjected to the strategy of OSMAC (one strain many compounds) with changes of cultivation status. Then, the work-flow led to the expansion of the alkaloid chemical diversity and subsequently induced the accumulation of four undescribed alkaloids, named raistrimides A-D (1-4), including three β-carbolines (1-3), one 2-quinolinone (4), and one new natural product, 2-quinolinone (5), along with five known alkaloid chemicals (6-10). A set of NMR techniques including 1H, 13C, HSQC and HMBC, along with other spectroscopic data of UV-Vis, IR and HRESIMS, were introduced to assign the plain structures of compounds 1-10. The absolute configuration of 1-3 were elucidated by means of X-ray crystallography or spectroscopic analyses on optical rotation values and experimental electronic circular dichroism (ECD) data. In addition, it was the first report on the confirmation of structures of 6, 7 and 9 by X-ray crystallography data. The micro-broth dilution method was applied to evaluate antimicrobial effect of all compounds towards Staphylococcus aureus, Escherichia coli, and Candida albicans. The results indicated compounds 1, 3 and 4 to be bioactive, which may be potential for further development of anti-antimicrobial agents. The finding in this work implied that OSMAC strategy was a powerful and effective tool for promotion of new chemical entities from P. raistrichii.

The Polyketides with Antimicrobial Activities from a Mangrove Endophytic Fungus Trichoderma lentiforme ML-P8-2.

Five new polyketides, including two chromones (1-2), two phenyl derivatives (4-5), and a tandyukusin derivative (6), along with five known polyketides (3 and 7-10) were isolated from mangrove endophytic fungus Trichoderma lentiforme ML-P8-2. The planar structures of compounds were elucidated via detailed 1D, 2D NMR, and HR-ESI-MS analysis. ECD spectra, optical rotation values calculation, and alkali hydrolysis were applied in the determination of the absolute configuration of the new compounds. In bioassays, 6 and 9 exhibited promising antifungal activities against Penicillium italicum, with an MIC value of 6.25 μM for both compounds. Moreover, 3 displayed moderate AChE inhibitory activity with an IC50 value of 20.6 ± 0.3 μM.

Nor-24-homoscalaranes, Neutrophilic Inflammatory Mediators from the Marine Sponge Lendenfeldia sp.

The marine sponge Lendenfeldia sp., collected from the Southern waters of Taiwan, was subjected to chemical composition screening, resulting in the isolation of four new 24-homoscalarane compounds, namely lendenfeldaranes R-U (1-4). The structures and relative stereochemistry of the new metabolites 1-4 were assigned based on NMR studies. The absolute configurations of compounds 1-4 were determined by comparing the calculated and experimental values of specific optical rotation. The antioxidant and anti-inflammatory activities of the isolated compounds were assayed using superoxide anion generation and elastase release assays. These assays are used to determine neutrophilic inflammatory responses of respiratory burst and degranulation. Compounds 2 and 4 inhibited superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB) with IC50: 3.98-4.46 μM. Compounds 2 and 4 inhibited fMLP/CB-induced elastase release, with IC50 values ranging from 4.73 to 5.24 μM. These findings suggested that these new 24-homoscalarane compounds possess unique structures and potential anti-inflammatory activity.

Ent-Herqueidiketal and epi-Peniciherqueinone Isolated from a Mushroom Derived Fungus Penicillium herquei YNJ-35.

A new polyaromatic metabolite, ent-herqueidiketal (1), and a new phenalenone derivative, epi-peniciherqueinone (2), along with twelve known compounds 3-14, were isolated from the fungus Penicillium herquei YNJ-35, a symbiotic fungus of Pulveroboletus brunneopunctatus collected from Nangunhe Nature Reserve, Yunnan Province, China. The structures of 1-14 and the absolute configurations of 1 and 2 were determined by their spectroscopic data or by their single-crystal X-ray diffraction analysis or optical rotation values. Compound 1 showed strong antibacterial activity against Staphylococcus aureus (ATCC 29213) with minimum inhibitory concentration (MIC) of 8 μg/mL. In the cytotoxicity assays, compound 1 showed weak inhibitory activity against breast cancer MCF-7 and mice microglial BV2 cells with half maximal inhibitory concentration (IC50) of 17.58 and 29.56 μM; compound 14 showed stronger cytotoxicity against BV2 and MCF-7 cells with IC50 values of 6.57 and 10.26 μM.

Evaluation of Marketed Rosemary Essential Oils (Rosmarinus officinalis L.) in Terms of European Pharmacopoeia 10.0 Criteria.

Various pure rosemary essential oil containing commercial products are in demand for their health-promoting and cosmetic claims in Türkiye. Although they are natural and harmless, they should be in compliance with European Pharmacopoeia (EP) criteria. Therefore, in this study, 15 rosemary oil samples sold in pharmacies, herbal shops, and online platforms in Türkiye were investigated in terms of "Rosemary Oil" EP 10.0. monograph criteria. In the current study, we aimed to evaluate the current quality status of rosemary essential oils in the Turkish market. Appearance, fatty oils and resinified essential oils, relative density, refractive index, optical rotation, and acid value tests were performed according to EP 10.0 and compared with the given standards. In addition, thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) analysis were conducted on all samples for advanced understanding of their phytochemical profile and harmony with EP standards. Fifteen pure rosemary oil-containing products from the Turkish market were evaluated. All of the samples were licensed as cosmetic products in Türkiye via the Ministry of Health. 83.1 to 96.9% of the ingredients of all samples were determined via GC-MS analysis. Results demonstrated that none of the samples from the Turkish rosemary essential oil market fully complied with the EP rosemary oil monograph standards. Considering our data, it was revealed that enhanced regulations and auditing mechanisms are needed to improve the quality of products. When the difference between the sources of purchase is assessed, pharmacies are still better locations to obtain such products.

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus.

A new antibacterial 3-monoacyl-sn-glycerol, nostochopcerol (1), was isolated from a cultured algal mass of the edible cyanobacterium Nostochopsis lobatus MAC0804NAN. The structure of compound 1 was established by the analysis of NMR and MS data while its chirality was established by comparison of optical rotation values with synthetically prepared authentics. Compound 1 inhibited the growth of Bacillus subtilis and Staphylococcus aureus at MIC of 50 μg/mL and 100 μg/mL, respectively.

Sesquiterpene Lactones with Anti-Inflammatory Activity from the Halophyte Sonchus brachyotus DC.

There were five sesquiterpene lactones, belonging to the eudesmanolide class, isolated from the halophyte Sonchus brachyotus DC. The structures of the compounds were determined using spectroscopic methods, including 1D and 2D NMR spectra, MS data, and optical rotation values. Compounds 4 and 5 were characterized by the position of p-hydroxyphenylacetyl group in the sugar moiety. In the evaluation of anti-inflammatory effects on LPS-activated RAW264.7 macrophages, compound 1, 5α,6βH-eudesma-3,11(13)-dien-12,6α-olide, potently suppressed the expression of iNOS and COS-2, as well as the production of TNF-α, IL-6, and IL-10. Treatment of 1 regulates the Nrf2/HO-1 pathway.

Eremophilane sesquiterpenoids from the endophytic fungus Curvularia lunata BCC76963

A chemical investigation on broth and mycelia extracts of the endophytic fungus Curvularia lunata BCC76963 led to the isolation of five new eremophilane sesquiterpenoids, curvuleremophilanes A−D (1–4) and septeremophilane I (5), one new conjugated unsaturated fatty acid, (6S,2E,4E)-8-hydroxy-4,6-dimethylocta-2,4-dienoic acid (6), and one new phenylacetic acid derivative, 4′-chlorocurvulin (8), along with ten known compounds. The chemical structures were elucidated based on the analyses of HRESIMS and NMR spectroscopic data. The absolute configurations of eremophilanes were assigned by the evidence from NOESY correlations, chemical conversion, optical rotation values, and ECD spectroscopic data in conjunction with biogenetic considerations. In addition, the absolute stereochemistry of compound 5 was confirmed by X-ray crystallography. Curvuleremophilane A (1), dendryphiellin I (10), chaetopenoid B (11), and bipolaroxin (12) displayed antimalarial activity against Plasmodium falciparum K1 with IC50 values in a range of 3.64–7.77 μM and antibacterial activity against Bacillus cereus and Staphylococcus aureus with MIC values in a range of 3.13–12.50 and 1.56–25.00 μg/mL, respectively. These compounds, except for compound 11, also showed cytotoxicity against NCI-H187 and Vero cells with respective IC50 values in a range of 2.76–3.97 and 2.34–4.67 μM.

On the Cation-π capabilities of infinitene (∞). Evaluation of bonding and circular dichroism properties for Infinitene-Ag(I)n (n = 1–4) complexes from relativistic DFT calculations

The helicoidal π-conjugated structure from helicenes is able to feature cation-π bonding towards Ag(I) atoms, resulting in the variation of their inherent high optical rotation values. Recently, the characterization of infinitene ([12]infinitene) as two fused [6]helicene structures with a central crossover section suggests the extension of such coordination characteristics to large and more complex structural landscapes. Herein, we evaluated the possible cation-π features of infinitene towards one to four silver cations from density functional calculations and their role in the optical rotation of the infinity-shaped backbone. The nature of the cation-π interaction for infinitene, shows a favorable formation of single and multiple Ag(I) aggregation, with a slight distortion of the structural backbone. Hence, the formation of cation- π complexes in infinitene is plausible, suggesting the expansion of its chemistry towards the formation of metal complexes in fused helicene species.

Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses.

Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a “heat shock metabolite (HSM)” by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC50 values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC50 values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC50 concentrations.

Macathiohydantoins P–R, three new thiohydantoin derivatives from Maca (Lepidium meyenii)

Three new thiohydantoins with a 2-thioxoimidazolidin-4-one nucleus, named macathiohydantoins P–R (1–3), along with one known analog (4), were isolated from the roots of Lepidium meyenii. Their structures were elucidated by means of analysis of extensive spectroscopic data, including 1D NMR, 2D NMR and HRESIMS. The thiohydantoins (1–4) were isolated as racemic mixtures, which were further separated by chiral semi-preparative HPLC to afford the corresponding enantiomers. Their absolute configuration of C-5 was assigned by comparison of optical rotation values with those reported in the literature. All thiohydantoin derivatives were evaluated for their cytotoxicities against five human cancer cell lines.