Heliannuols are a unique class of sesquiterpenes isolated mostly from Helianthus annuus, commonly known as sunflower. The interesting allelopathic properties, combined with their unprecedented carbon ...skeletons, have drawn wide attention to phytochemistry and synthetic groups. So far, 14 heliannuols (heliannuols A–N) have been described in the literature, although some of them have not yet been validated by total synthesis. Moreover, the structural proposal of some compounds was based on the similarity of NMR data reported for previously isolated analogues (which in many instances turned out to be incorrect), coupled with little or no stereochemical analysis. Consequently, the structural reassignment is a recurring theme in heliannuol’s family. Through a rigorous and comprehensive quantum chemical simulation of NMR parameters, encompassing an integrated ANN-PRA/DP4+ tandem approach, we intended to advance unexplored directions regarding the structure of the entire heliannuol family. Furthermore, we found that the size of the fused ring significantly influences the signals corresponding to the aromatic ring, making this discovery an excellent diagnostic tool for quickly determining the core structure of these compounds.
Vibrational circular dichroism (VCD) is one of the most powerful techniques to assess the stereochemistry of chiral molecules in solution state. The need for quantum chemical calculations to ...interpret experimental data, however, has precluded its widespread use by non-experts. Herein, we propose the search and validation of IR and VCD spectral markers to circumvent the requirement of DFT calculations allowing for absolute configuration assignments even in complex mixtures. To that end, a combination of visual inspection and machine learning based methods is used. Monoterpene mixtures are selected for this proof-of-concept study.
A combination of visual inspection and machine learning is used to identify IR/VCD spectral markers to determine composition and absolute configuration of terpenes in complex mixtures.
Nuclear magnetic resonance (NMR) spectroscopy can provide detailed information about the chemical structure and stereochemistry of a molecule. However, this technique alone may not always be ...sufficient to assign with confidence the relative configuration of a secondary metabolite. In some cases, additional experiments, such as the Density Functional Theory (DFT) calculation of the chemical shifts for the molecule, may be necessary to support the assignment. An endoperoxide (1) isolated from Plakortis angulospiculatus has a structure containing four stereogenic centers. The stereochemistry of 1 was proposed based on the biogenetic pathway and optical rotation correlations. Herein, we describe the structure analysis of the natural 1 by quantum NMR calculations for the first time.
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Oral squamous cell carcinoma (OSCC) is one of the ten most common types of cancer worldwide. Plants of the genusPiper are used in traditional medicine to treat cancer, and they have a ...vast diversity of phytochemicals with cytotoxic potential.
Purpose and Study Design: In this work, we analyzed the cytotoxic and selective potential of extracts and semipurified fractions of Piper mollicomum (PM), Piper truncatum (PT), Piper cernuum (PC), Piper arboreum (PA), and Piper cabralanum (PCa) using three different OSCC cell lines (SCC4, SCC9 and SCC25), and we measured their in vivo toxicities and conducted chemical analyses of their active fractions.
The dichloromethane fractions of the crude methanolic extracts of the leaves of PM(-L-D), PC(-L-D) and PCa(-L-D) exhibited notable IC50 values of 94.2, 47.2 and 47.5 μg/mL, respectively, and all three of these extracts were more active than carboplatin (172.3 μg/mL). The most selective fraction was PC-L-D, which exhibited SI > 4.5; less than 5% hemolysis; and no significant alterations in in vivo acute toxicology. The major constituents in active fractions were lignans (PC-L-D and PCa-L-D) and chromenes (PM-L-D).
PC-L-D demonstrated great potential for further development as an anticancer drug and could be the key to developing more effective and less toxic therapies against oral cancer.
In the early 2000s, the first articles regarding the calculation of NMR parameters for natural products appeared in the literature. Since then, modelling 1H and 13C chemical shifts and spin–spin ...coupling constants for this class of compounds has experienced a remarkable increase in precision, accessibility, and application, leading to considerable advances in the field. More recently, significant contributions from several authors have led to continuous growth in this research field, updating and broadening the simulation of NMR parameters, in particular with the application of new techniques for data treatment. Nowadays, such studies are routinely found in the high impact literature. In this review, we intend to cover the general guidelines and the main advances in NMR calculations of natural products published since 2012. We intend to address the bottlenecks of quantum chemical calculations of NMR parameters, including mathematical definitions, updates, and a discussion of relevant examples, and to highlight novel tools, for example DU8+, CP3, DP4, DP4+ and J-DP4. We will cover all aspects of NMR simulation focusing on natural products, from the fundamentals to the new computational toolboxes available, combining advanced quantum chemical calculations with complex upstream data processing and machine learning.
Stereochemical determinations based solely on the comparison of optical rotation (OR) measured at a single wavelength may commonly result in misassignments. Herein, we use vibrational and electronic ...CD, NMR, OR, and DFT calculations, to confirm the absolute configuration (AC) of the cytotoxic marine polyketides spongosoritin A (
1
) and 9,10-dihydrospongosoritin A (
2
) as (−)-(6
R
,8
R
) and (−)-(6
R
,8
S
), respectively. The AC of natural
1
and
2
has so far relied upon comparisons of OR values only. Besides showing the dependence of OR on achiral structural features, such as
E
/
Z
double bond geometries, an IR spectral marker is provided to help distinguish the geometric isomers of related molecules.
A combination of spectroscopic methods reveals the dependence of the chiroptical properties of spongosoritins on achiral structural features.
•Phorbas amaranthus extract as natural products library;•DryLab® software for Design of Experiments in association with scouting systems;•Sixty-four metabolites chemically characterized by ...LC-HRMS;•New metabolites inferred based on Global Natural Product Social Molecular Networking (GNPS).
Phorbas is a widely studied genus of marine sponge and produce structurally rich cytotoxic metabolites. Still, only few studies have assessed metabolites present in Brazilian species. To circumvent redundancy, in this work, we applied and herein report the use of a scouting liquid chromatographic system associate to the design of experiment produced by the DryLab® software to obtain a fast and efficient chromatographic separation of the active hexane fraction, further enabling untargeted high-resolution mass spectrometry (HRMS) data. To this end, a crude hydroalcoholic extract of the sponge Phorbas amaranthus collected in Brazilian coast was prepared and partitioned. The cytotoxicity of the crude extract and the fractions was evaluated using tumor cell culture models. Fragmentation pathways assembled from HRMS data allowed the annotation of 18 known Phorbas metabolites, while 17 metabolites were inferred based on Global Natural Product Social Molecular Networking (GNPS), matching with a further 29 metabolites annotated through molecular subnetwork. The workflow employed demonstrates that chromatographic method development can be accelerated by the use of automated scouting systems and DryLab®, which is useful for profiling natural product libraries, as well as data curation by molecular clusters and should be incorporated to the tools of natural product chemists.
The skeleton of the helianane's family is an unsolved controversial topic. Recent synthetic studies and
13
C NMR structural analysis have demanded for an amendment of helianane to the open ring ...curcudiol. However, some authors argue that the original helianane structure, a benzofused eight-membered ether ring system, cannot be ruled out immediately without further spectral analyses of curcudiol and helianane. The fact that this compound is extremely rare, obtained only from marine organisms, makes remote the possibility of reisolation. Therefore, we decided to approach this problem computationally. Herein, we performed a complementary quantum mechanical study in order to provide more information about the helianane's actual skeleton. Our
13
C NMR chemical shifts calculations suggests that the curcudiol structure is more likely to be the correct one. In addition, we simulated the formation pathways for both products starting from the known biosynthetic precursor. The results show that curcudiol is around 8.0 kcal mol
−1
more stable than the originally proposed helianane structure.
Comprehensive work suggesting the amendment of helianane to the open ring curcudiol by means of computational spectroscopy and thermodynamic reasons.
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•Cerrado Brazilian plants ethanolic extract as natural products library.•High specificity affinity-based assay for PEPCK.•Eleven ligands chemically characterized by LC-HRMS.
In T. ...cruzi, a causative agent of Chagas disease, phosphoenolpyruvate carboxykinase (TcPEPCK) is associated with carbohydrate catabolism. Due to its importance in the metabolism of the parasite, it has become a promising target for the development of new drugs against Chagas disease. Aiming to investigate different approaches for ligands screening, TcPEPCK was immobilized on amine-terminated magnetic beads (TcPEPCK-MB) and kinetically characterized by liquid chromatography tandem mass spectrometry activity assay with a KMapp value of 10 ± 1 μM to oxaloacetate as substrate. Natural products library affords highly diverse molecular frameworks through their secondary metabolites, herein a ligand fishing TcPEPCK-MB assay is described for prospecting ligands in four ethanolic extracts of Brazilian Cerrado plants: Qualea grandiflora (Vochysiaceae), Diospyros burchellii (Ebenaceae), Anadenanthera falcata (Fabaceae) and Byrsonima coccolobifolia (Malpighiaceae). The chemical characterization of eleven identified ligands was carried out by liquid chromatography tandem high-resolution mass spectrometry experiments. Senecic acid, syneilesinolide A, phytosphingosine and vanillic acid 4-glucopyranoside are herein reported for the first time for Q. grandiflora, D. burchellii, A. falcata, respectively. In addition, the specificity of the assay was observed since only catechin was fished out from the ethanolic extract of B. coccolobifolia leaves, despite the presence of epicatechin epimer.
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