2D NMR Spectroscopy Research Articles

Two new naturally dimers constituent from Indonesian Sesbania grandiflora plant and their bioactivity

Abstract A new dimer of natural isoflavonoid along with some known flavonoid compounds was successfully isolated from the roots of Indonesian Sesbania grandiflora plant using ethyl acetate extraction. The new compound specified as naturally bi-isoflavonoid with (4→6) inter-isoflavanyl linkage and four known flavonoids xenognosin B, liquiritigenin, 7,2′4′-trihydroxyisoflavone, demethylvestitol, and 1,1′-bi-2-naphthol was isolated and the antituberculosis activity of the compounds was studied. The structure of all compounds was elucidated with the aid of 1D and 2D NMR, UV spectroscopy, and HRESI mass spectrometry. The data obtained were also compared with the previous published data. Among compounds, 1,1′-bi-2-naphthol was found to exhibit the highest activity against Mycobacterium tuberculosis H37Rv with the MIC’s value of 10.9 µM while the biisoflavonoid with (4→6) inter-isoflavanyl linkage showed moderate activity with the MIC’s value of 92.2 nM, compared with isozianid as a positive control with the MIC’s value of 0.569 nM. It is worth to note that 1,1′-bi-2-naphthol and biisoflavonoid with (4→6) inter-isoflavanyl linkage were isolated for the first time from a natural source. Both compounds have been previously reported as synthetic compounds, which is synonymous with 3,4- trans-4-[(3S)-7,2′-dihydroxy-4′-methoxyisoflavan-6-yl]-7,2′-dihydroxy-4′-methoxyisoflavan and 1,1′-bi-2-naphthol, respectively. In this respect, the results of this study suggest that the roots of S. grandiflora is a potential source of new natural product compounds, with promising bioactivities.

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains.

Several under-explored Aspergillus sp. produce intriguing heptapeptides containing a γ-aminobutyric acid (GABA) residue with as yet unknown biological functions. In this study, a new GABA-containing heptapeptide - unguisin J (1) - along with known unguisin B (2) were isolated from a solid culture of Aspergillus heteromorphus CBS 117.55. The structure of compound 1 was elucidated by extensive 1D and 2D NMR spectroscopic analysis including HSQC, HMBC, COSY, and 2D NOESY as well as HRESIMS. The stereochemistry of 1 and 2 was determined by Marfey's method. A biosynthetic gene cluster (BGC) encoding unguisins B and J was compared to characterized BGCs in other Aspergillus sp. Since the unguisin family of heptapetides incorporate different amino acid residues at different positions of the peptide, the A and C domains of the UngA NRPS were analyzed in an attempt to understand the lack of substrate specificity observed.

Scaffolded Structure Determination Activities Utilizing 2D NMR Spectroscopy of Simple Organic Molecules

Scaffolded Structure Determination Activities Utilizing 2D NMR Spectroscopy of Simple Organic Molecules

Sesquiterpenes and α-pyrones from an endophytic fungus Xylaria curta YSJ-5

Chemical investigation of the culture extract of an endophyte Xylaria curta YSJ-5 from Alpinia zerumbet (Pers.) Burtt. et Smith resulted in the isolation of eight previously undescribed compounds including five eremophilane sesquiterpenes xylarcurenes A-E, one norsesquiterpene xylarcurene F, and two α-pyrone derivatives xylarpyrones A-B together with eight known related derivatives. Their chemical structures were extensively established based on the 1D- and 2D-NMR spectroscopic analysis, modified Mosher's method, electronic circular dichroism calculations, single-crystal X-ray diffraction experiments, and the comparison with previous literature data. All these compounds were tested for in vitro cytotoxic, anti-inflammatory, α-glucosidase inhibitory, and antibacterial activities. As a result, 6-pentyl-4-methoxy-pyran-2-one was disclosed to display significant antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with minimal inhibitory concentration value of 6.3 μg/mL.

Threading a Linear Molecule Through a Macrocycle Thanks to Boron: Optical Properties of the Threaded Species and Synthesis of a Rotaxane.

Two BODIPYs and two boron β-diketonates were threaded through a macrocycle bearing a 2,2'-biphenol unit, showing thus the ability of boron to act as a gathering atom. The new threaded species were characterized by 1D and 2D NMR spectroscopy as well as by X-ray crystallography for one of them and their properties rationalized with quantum chemistry to unravel the vibronic contributions. The BODIPYs exhibited interesting fluorescence features with quantum yields up to 91 % and enhanced photostability compared to their non-threaded homologues. A rotaxane was synthesized using this threading strategy after stoppering and removing the boron with potassium hydroxide.

Threading a Linear Molecule Through a Macrocycle Thanks to Boron: Optical Properties of the Threaded Species and Synthesis of a Rotaxane

AbstractTwo BODIPYs and two boron β‐diketonates were threaded through a macrocycle bearing a 2,2’‐biphenol unit, showing thus the ability of boron to act as a gathering atom. The new threaded species were characterized by 1D and 2D NMR spectroscopy as well as by X‐ray crystallography for one of them and their properties rationalized with quantum chemistry to unravel the vibronic contributions. The BODIPYs exhibited interesting fluorescence features with quantum yields up to 91 % and enhanced photostability compared to their non‐threaded homologues. A rotaxane was synthesized using this threading strategy after stoppering and removing the boron with potassium hydroxide.

Novel Flavonol Alkaloids in Green Tea: Synthesis, Detection, and Anti-Alzheimer's Disease Effect in a Transgenic Caenorhabditis elegans CL4176 Model.

Novel N-ethy-2-pyrrolidinone-substituted flavonols, myricetin alkaloids A-C (1-3), quercetin alkaloids A-C (4a, 4b, and 5), and kaempferol alkaloids A and B (6 and 7), were prepared from thermal reaction products of myricetin, quercetin, kaempferol─l-theanine, respectively. We used HPLC-ESI-HRMS/MS to detect 1-7 in 14 cultivars of green tea and found that they were all present in "Shuchazao," "Longjing 43", "Fudingdabai", and "Zhongcha 108" green teas. The structures of 1-4 and 6 were determined by extensive 1D and 2D NMR spectroscopies. These flavonol alkaloids along with their skeletal flavonols were assessed for anti-Alzheimer's disease effect based on molecular docking, acetylcholinesterase inhibition, and the transgenic Caenorhabditis elegans CL4176 model. Compound 7 strongly binds to the protein amyloid β (Aβ1-42) through hydrogen bonds (BE: -9.5 kcal/mol, Ki: 114.3 nM). Compound 3 (100 μM) is the strongest one in significantly extending the mean lifespan (13.4 ± 0.5 d, 43.0% promotion), delaying the Aβ1-42-induced paralysis (PT50: 40.7 ± 1.9 h, 17.1% promotion), enhancing the locomotion (140.0% promotion at 48 h), and alleviating glutamic acid (Glu)-induced neurotoxicity (153.5% promotion at 48 h) of CL4176 worms (p < 0.0001).

Aspercitrininone A, novel antibacterial polyketide featuring unusual spiral skeleton from Aspergillus cristatus

Aspercitrininone A (1), a novel polyketide featuring an unprecedented tetracyclic 6/6/6/5 spiral skeleton, was obtained from the rice fermentation cultures of the fungus Aspergillus cristatus together with five known compounds (2–6). Their structures were determined by HRESIMS data, 1D and 2D NMR spectroscopic analysis, and electronic circular dichroism (ECD) calculations. Aspercitrininone A was revealed as a new type of C/D cycle spiral structure and an unusual addition product of o-quinoid form citrinin with 2-methylterrefuranone. Compounds 1, 4, and 5 exhibited potent antibacterial activities with minimal inhibitory concentration (MIC) values from 13.2 to 67.3 μg/mL against four strains of human pathogenic bacteria in vitro.

Okeanic acid–A, a trihydroxy fatty acid from the Okinawan cyanobacterium Okeania hirsuta

Trihydroxy fatty acids are oxidative metabolites of polyunsaturated fatty acids isolated from plants, bacteria, fungi, and microalgae and have a variety of biological activities. In this study, a new trihydroxy fatty acid, okeanic acid–A (1), was isolated together with malyngic acid (2) and 15,16-dihydromalyngic acid (3) from the cyanobacterium Okeania hirsuta collected in Okinawa, Japan. The planar structure of 1 was elucidated by detailed analyses using high-resolution ESI-MS and 1D and 2D NMR spectroscopy. The absolute configurations of the hydroxy groups in 1 were determined unambiguously by chemical derivatisation and a modified Mosher’s method. These cyanobacterial trihydroxy fatty acids (1–3) have identical configurations at their respective trihydroxy parts. Okeanic acid–A (1) showed mild growth-inhibitory activity against the marine diatom Nitzschia amabilis.

Tunable Zinc-Mediated Reductive Cyclization of Diastereomeric 3-Nitro-4-phenacyl-2-(trihalomethyl)chromanes to Fused Pyrroline N-Oxides, Pyrrolines, and Pyrrolidines.

Reductive cyclization of trans,trans- and trans,cis-isomers of the 2-CF3-substituted 3-nitro-4-phenacylchromanes with Zn-based reductive systems, depending on the conditions, affords 4-CF3-substituted 1,3a,4,9b-tetrahydrochromeno[3,4-b]pyrrole 3-oxides, 1,3a,4,9b-tetrahydrochromeno[3,4-b]pyrroles, or 1,2,3,3a,4,9b-hexahydrochromeno[3,4-b]pyrroles in good yields without changing the relative configuration of the pyran ring. A similar process involving the 2-CCl3-substituted 3-nitro-4-phenacylchromanes is accompanied by reductive dehalogenation to form the corresponding 4-dichloromethyl-substituted fused chromanes along with the 3-(2-hydroxyaryl)-2-(2,2-dichlorovinyl)-5-phenyl-2H-pyrroline 1-oxides as pyran ring opening products. The structure and relative configuration of the obtained products was reliably confirmed by X-ray diffraction analysis and 2D NMR spectroscopy.

Sterically Controlled Synthesis of Amine-Free CsPbBr3 Nanoplatelets for Stable, Pure-Blue Light Emission.

Metal halide perovskite nanoplatelets (NPLs) have demonstrated excellent optical properties for light-emitting applications and achieved tunable blue luminescence through thickness control. However, their translation into electronic devices has lagged behind due to poor colloidal and film stability. The main reason for this is the deprotonation of their surface-capped ammonium passivating ligands, resulting in NPL aggregation. Here we report the first facile synthesis of amine-free pure-blue CsPbBr3 NPLs with outstanding thermal and light stability. This is achieved by utilizing an amine-free phosphine oxide route with a surface capping molecule exhibiting large steric hindrance to prevent NPL aggregation. Two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy suggests slower ligand exchange in amine-free NPLs compared to the conventional NPLs, which can be attributed to the strong binding strength of the designated ligand. Consequently, the amine-free NPLs exhibited superior stability against radiation, heat and moisture. We further demonstrate the importance of acid-base equilibrium in this amine-free synthesis route. Through solvent neutralization and passivation with various alkali carbonates, the resulting NPLs attained near-unity photoluminescence quantum yield (PLQY) and pure blue emission.

Antioxidant activity of spirostanol saponins from Allii Macrostemonis Bulbus and their contents in different origins and processed products

Allii Macrostemonis Bulbus (AMB), a traditional Chinese edible and medicinal plant, is considered beneficial to health. In this study, we isolated and purified nine steroidal saponins (compounds 1–9) from AMB. Their structures were characterized using physicochemical properties, HR-ESI-MS, 1D and 2D NMR spectroscopy. Among these compounds, compounds 1–5 were newly discovered named macrostemonoside U-Y, respectively. We assessed the in vitro antioxidant properties of the nine steroidal saponins through free radical scavenging and reducing power assays. This provides options for developing natural antioxidants. Additionally, an HPLC-ELSD quantitative analysis method was developed for the nine saponins in 12 batches of AMB from different origins and processing methods. The results showed that the contents of the nine steroidal saponins in AMB varied greatly among different growing environments and processing methods.

Koningipyridines A and B, two nitrogen-containing polyketides from the fungus Trichoderma koningiopsis SC-5

Two novel koninginin derivatives, koningipyridines A and B (1 and 2), along with four known compounds (3˗6) were isolated from the EtOAc extract of the endophytic fungus Trichoderma koningiopsis SC-5. Among them, koningipyridine A featured an unprecedented pentacyclic ketal skeleton with the formation of a fascinating 6/6/5/6/5 fused ring system and shared a characteristic pyridine core, which represents the first example of nitrogen-containing koninginin-type natural product. Moreover, koningipyridine B was the first member in the koninginin family sharing a unique 6/6/5 dihydropyridine skeleton, and it was suggested to be the critical biosynthetic precursor of koningipyridine A. The structures of 1 and 2 were elucidated by the interpretation of 1D and 2D NMR spectroscopy, HRESIMS data, as well as theoretical calculations of 13C NMR and electronic circular dichroism (ECD). Moreover, all isolates were screened for antimicrobial activities against Staphylococcus aureus, MRSA, and Escherichia coli as well as the cytotoxic effects against three cancer cell lines (A549, Hela, and HepG2).Graphical

Discovery of bi-4-methoxycarbonyl-2-quinolone and evaluation of its anti-inflammatory and anti-cancer activity in vitro

A novel alkaloid with a hexa-tetra-hexa-cyclic skeleton, Bi-4-methoxycarbonyl-2-quinolone (1), was discovered during the investigation of Brucea javanica. Additionally, six known alkaloids (2–7) were also found. The chemical structures of these compounds were identified using HRESIMS and 1D and 2D NMR spectroscopic analysis. Additionally, the absolute configuration of the new compound 1 was determined through X-ray single crystal diffraction. Compound 1 exhibited significant anti-inflammatory activity in RAW264.7 cells and demonstrated promising anti-cancer effects in Lewis cells.

A new lanosyl guanidine from Vertebrata lanosa with anti-inflammatory activity

N-Lanosyl guanidine (1), a new bromophenol containing a guanidine moiety was isolated from the red alga Vertebrata lanosa (L.) T.A. Christensen, which is frequently used for cosmetic purposes. Structure elucidation was performed by means of mass spectrometry as well as 1D and 2D NMR spectroscopy. Due to its structural features, 1 might share a common biosynthetic route with known bromophenolic ureido derivatives. Regarding potential bioactivities, 1 has shown clear anti-inflammatory properties, reducing cytokine release in lipopolysaccharide-stimulated phorbol 12-myristate 13-acetate-differentiated THP-1 macrophages. No signs of toxicity were observed, in either the cell line nor in the nematode Caenorhabditis elegans. However, 1 was inactive against the gram-negative bacterium Pseudomonas aeruginosa.

Allostreptopyrroles A-E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384.

Five new β-alkylpyrrole derivatives, allostreptopyrroles A-E (1-5), were isolated from the culture broth of Allostreptomyces RD068384. Their structures were elucidated by 1D and 2D NMR spectroscopic analyses, HRESIMS, and chemical derivatization. The absolute configurations of compounds 2 and 3 were predicted by comparison of experimental and calculated specific rotation data. Compounds 1-5 are the first examples of natural pyrroles substituted by formyl and carboxyl functionalities. Compounds 1, 4, and 5 showed cytotoxicity against Kasumi-1 human acute myeloblastic leukemia cells with IC50 values of 103, 105, and 105 μM, respectively, which are less active than the anticancer agent cisplatin, with an IC50 value of 70 μM.

Diterpenoids target SARS-CoV-2 RdRp from the roots of Euphorbia fischeriana Steud.

Currently, the development of new antiviral drugs against COVID-19 remains of significant importance. In traditional Chinese medicine, the herb Euphorbia fischeriana Steud is often used for antiviral treatment, yet its therapeutic effect against the COVID-19 has been scarcely studied. Therefore, this study focuses on the roots of E. fischeriana Steud, exploring its chemical composition, antiviral activity against COVID-19, and the underlying basis of its antiviral activity. Isolation and purification of phytochemicals from E. fischeriana Steud. The elucidation of their configurations was achieved through a comprehensive suite of 1D and 2D NMR spectroscopic analyses as well as X-ray diffraction. Performed cytopathic effect assays of SARS-CoV-2 using Vero E6 cells. Used molecular docking to screen for small molecule ligands with binding to SARS-CoV-2 RdRp. Microscale thermophoresis (MST) was used to determine the dissociation constant Kd. Ultimately, nine new ent-atisane-type diterpenoid compounds were isolated from E. fischeriana Steud, named Eupfisenoids A-I (compounds 1-9). The compound of 1 was established as a C-19-degraded ent-atisane-type diterpenoid. During the evaluation of these compounds for their antiviral activity against COVID-19, compound 1 exhibited significant antiviral activity. Furthermore, with the aid of computer virtual screening and microscale thermophoresis (MST) technology, it was found that this compound could directly bind to the RNA-dependent RNA polymerase (RdRp, NSP12) of the COVID-19, a key enzyme in virus replication. This suggests that the compound inhibits virus replication by targeting RdRp. Through this research, not only has our understanding of the antiviral components and material basis of E. fischeriana Steud been enriched, but also the potential of atisane-type diterpenoid compounds as antiviral agents against COVID-19 has been discovered. The findings mentioned above will provide valuable insights for the development of drugs against COVID-19.

Synthesis and studies of covalently linked (BODIPY)2-3-pyrrolyl BODIPY triads.

Two novel covalently linked triads containing one 3-pyrrolyl BODIPY unit and two BODIPY units were synthesized over a sequence of steps using meso-(p-formylphenyl)-3-pyrrolyl BODIPY as a key precursor. Both triads were thoroughly characterized and studied by using HRMS, 1D and 2D NMR spectroscopy, X-ray crystallography, absorption, steady-state and time-resolved fluorescence, cyclic voltammetry, and DFT/TD-DFT techniques. X-ray structural analysis of these triads revealed that the dipyrrin units of both meso-BODIPY and 3-pyrrolyl BODIPY were oriented in the same plane whereas the dipyrrin unit of the α-BODIPY unit was oriented almost perpendicular to that of the 3-pyrrolyl BODIPY unit. Both triads showed two well-separated absorption bands corresponding to BODIPY and 3-pyrrolyl BODIPY units in the 510-675 nm region. In these triads, the BODIPY unit absorbs in the higher energy region and acts as an energy donor whereas the 3-pyrrolyl BODIPY unit absorbs in the lower energy region and acts as an energy acceptor. Steady-state and time-resolved fluorescence studies of these triads indicated the possibility of intramolecular singlet-singlet energy transfer with almost 98% efficiency from the BODIPY units to the 3-pyrrolyl BODIPY unit upon selective excitation of the BODIPY unit in both triads. DFT and TD-DFT investigations corroborated the experimental findings.

TADDOL-based P,S-bidentate phosphoramidite ligands in palladium-catalyzed asymmetric allylic substitution.

A series of easy-to-prepare and modular chiral P,S-bidentate phosphoramidites were synthesized. With respect to Pd(II), these ligands showed the ability to form stable P,S-chelate allylic complexes. The structures of the ligands and their complexes were confirmed by 2D NMR spectroscopy and single-crystal X-ray diffraction. These chiral inducers provided up to 99% ee in the Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate with C- and N-nucleophiles and up to 94% ee in the Pd-mediated allylic alkylation of cinnamyl esters with β-ketoesters and 2,5-dimethylpyrrole. Furthermore, up to 92% ee with quantitative conversion and chemo- and regioselectivity was achieved in the rare reaction between 2-(diethoxyphosphoryl)-1-phenylallyl acetate and aniline. The effects of the structural parameters, reaction conditions and ligand-to-metal ratio on the catalytic results are discussed. It was shown that the ligands surpass their analogues with different denticity.

The structural characterization and UV-protective properties of an exopolysaccharide from a Paenibacillus isolate.

Overexposure to ultraviolet (UV) light is known to cause damage to the skin, leading to sunburn and photo-aging. Chemical sunscreen products may give rise to health risks including phototoxicity, photosensitivity, and photosensitivity. Natural polysaccharides have attracted considerable interests due to diverse biological activities. A novel polysaccharide isolated was purified and structurally characterized using chemical methods followed by HPLC, GLC-MS, as well as 1D and 2D NMR spectroscopy. The photoprotective effect of the EPS on UVB-induced damage was assessed in vitro using cultured keratinocytes and in vivo using C57BL/6 mouse models. The average molecular weight of the EPS was 5.48 × 106Da, composed of glucose, mannose and galactose residues at a ratio of 2:2:1. The repeating units of the EPS were →3)-β-D-Glcp (1→3) [β-D-Galp (1→2)-α-D-Glcp (1→2)]-α-D-Manp (1→3)-α-D-Manp (1→. In cultured keratinocytes, the EPS reduced cytotoxicity and excessive ROS production induced by UVB irradiation. The EPS also exhibits an inhibitory effect on oxidative stress, inflammation, and collagen degradation found in the photodamage in mice. 1H NMR-based metabolomics analysis for skin suggested that the EPS partly reversed the shifts of metabolic profiles of the skin in UVB-exposed mice. The EPS exhibits skin photoprotective effects through regulating oxidative stress both in vivo and in vitro. Our findings highlight that the EPS is a potential candidate in sunscreen formulations for an efficient solution to UVB radiation.