GIAO 13C NMR Calculation Research Articles

Anti-Inflammatory Halogenated Monoterpenes from the Red Alga Portieria hornemannii.

The chemical investigation of a red alga Portieria hornemannii enabled the identification of three new halogenated monoterpenes (1-3) along with two previously identified metabolites (4 and 5). Their structures were determined by spectroscopic analysis and also by utilizing single-crystal diffraction analysis and quantum chemical calculation, as well as by comparison with literature data. Further corrections for dichloro and dibromo carbons using the sorted training set (STS) method were established in this study to significantly improve the accuracy in GIAO 13C NMR calculation of compounds 1-3. To discover the potential bioactive metabolites from P. hornemannii, the anti-inflammatory activities of all compounds were examined. Compounds 1 and 3-5 showed significant anti-inflammatory activity to inhibit the production of pro-inflammatory cytokines in the LPS-stimulated mature dendritic cells.

Undescribed 2,9-deoxyflavonoids and flavonol-diamide [3+2] adduct from the leaves of Aglaia odorata Lour. Inhibit nitric oxide production

Phytochemical study on the methanol extract of Aglaia odorata leaves resulted in the isolation of four previously undescribed compounds, including three 2,9-deoxyflavonoids and one flavonol-diamide [3 + 2] adduct, and 13 known compounds. The chemical structures of the four undescribed compounds were elucidated on the basis of their IR, HR-ESI-MS, 1D and 2D NMR, and ECD spectra. The results revealed an unprecedented 2,9-deoxyflavonoid framework, which was confirmed by TD-DFT, ECD, and GIAO 13C-NMR calculations using sorted training set methods. The 17 compounds were examined for their ability to inhibit NO production activity in cultured lipopolysaccharide-activated RAW264.7 cells with aglaodoratas A-C, odorine, and epi-odorine inhibiting NO production, with IC50 values in the range of 16.2–24.3 μM. The other investigated compounds had either weak or no activity.

Reassignment of the structures of pestalopyrones A–D

Pestalopyrones A–D are four unusual tricyclic pyrone derivatives with flexible chiral structures, isolated from the endophytic fungus Pestalotiopsis neglecta S3. The full elucidation of their structures was a challenging task, and remained unsolved in the original article. Herein, the relative configurations of pestalopyrones A and pestalopyrones B were unambiguously assigned by detailed analyses on spectroscopic data and GIAO 13C NMR calculation method with sorted training sets (STS). The planar structures of pestalopyrones C and pestalopyrones D were revised by reinterpretation of their reported spectroscopic data, and then their relative configurations were deduced by STS GIAO 13C NMR calculation and NOE analysis. The absolute configurations of all the mentioned compounds were determined by the comparison of their experimental and calculated ECD curves.

Oblongolides from endophytic fungus Phoma bellidis Neerg. harbored in Tricyrtis maculata (D. Don) J.F.Macbr.

Five previously undescribed oblongolides, namely phomaones A-E, along with four known compounds, were isolated from the endophytic fungus Phoma bellidis Neerg.. Their structures and absolute configurations were determined by extensive experimental spectroscopic methods as well as single crystal X-ray diffractions, ECD calculations and GIAO 13C NMR calculations. Phomaone A represent the first example of oblongolides with glycol directly linked by two C–C bonds, and its biosynthetic pathway were proposed. The cytotoxicity of obtained compounds was evaluated against human cancer cell lines MCF-7, DU145, and SW480. All compounds except phomaone A showed the cytotoxicity against MCF-7 with IC50 value ranging from 12.45 to 49.84 μM.

Concise total syntheses of two flavans and structure revision assisted by quantum NMR calculations.

A two-step protecting-group-free protocol for the synthesis of 3'-hydroxy-5,7-dimethoxy-4-O-2'-cycloflavan (1) and concise total synthesis of 4'-hydroxy-5,7-dimethoxy-4-O-2'-cycloflavan (8) enabled by a PTSA triggered bioinspired olefin isomerization/hemiacetalization/dehydration/[3 + 3]-type cycloaddition cascade reaction are reported. The successful synthesis of cycloflavan 8 along with GIAO 13C NMR calculations of flavan-4-ol 9 and cycloflavan 8 indicated the misassignment of the flavonoid isolated previously and realized the revision of its actual structure.

GIAO 13C NMR Calculation with Sorted Training Sets Improves Accuracy and Reliability for Structural Assignation.

GIAO 13C NMR calculation plays important roles in structural assignment for small organic molecules. Especially, higher accuracy and confidence are required for the structural assignation of complex organic molecules. In this GIAO 13C NMR calculation strategy, carbons were sorted according to their type of hybridization, radii of solvation cavity, or solvent interactions. The calculated shielding tensors of carbons in each sorted training set were linear-regressed with experimental data separately, and the obtained linear parameters were used to convert calculated shielding tensors into calculated chemical shifts. This approach shows significantly improved accuracy, especially for sp2 carbons, compared to conventional GIAO 13C NMR calculation protocols. A statistic-based probability algorithm was proposed to quantify the reliability of structural assignation. With empirical linear parameters for three commonly used NMR solvents as well as an easy-to-use script and a spreadsheet, this 13C NMR calculation protocol provides a useful tool for structural validation or assignation of ambiguous organic structures.

Reassignments of the structure DOBFs directed by CASE algorithms and GIAO 13C NMR computations

5,5′-dioxo-2,2′-bifurans (DOBFs) were noticed to possess the same NMR data with Phthalic Acid Esters (PAEs). Computer-assisted structure elucidation algorithms (CASE) followed by GIAO 13C NMR calculations were used to discuss the relationship between DOBFs and PAEs. The results led to the reassignments to DOBFs of which the true structures of DOBFs were the PAEs introduced by separation.

Serratane triterpenoids from Lycopodium complanatum and their anti-cancer and anti-inflammatory activities

Phytochemical investigation of the ethyl acetate fraction of Lycopodium complanatum led to eight new serratane triterpenoids (lycomplanatums A-H, 1–8), along with five known analogues (9–13). Their structures were elucidated by extensive spectroscopic methods, including 1D/2D NMR, HRESIMS, and DFT GIAO 13C NMR calculation. Among them, compounds 2 and 13 showed moderate antiproliferative effects against seven human cancer cell lines, especially for MCF-7 with IC50 values of 13.8–44.7 μM. Additionally, the compounds were screened for anti-inflammatory effects based on their inhibitory activities of nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 2 and 13 diminished NO production more potently than others in a concentration-dependent manner.

Cytotoxic triterpenoid glycosides from leaves of Cyclocarya paliurus

Three previously undescribed dammarane triterpenoid glycosides (1-3) along with five known analogues (4-8) were isolated from the leaves of Cyclocarya paliurus. Their structures and configurations were determined on the basis of comprehensive spectroscopic analyses, chemical hydrolysis and DFT GIAO 13C NMR calculation. All the isolates were evaluated cytotoxic activities against seven human cancer cell lines (MCF-7, PC-3, Du145, NCI-H1975, PC-9, SKVO3 and HepG2). Moreover, compound 4 showed a wide spectrum of cytotoxicity against human cancer cells with IC50 values ranging from 11.31 to 29.51 µM.

Effect of indole alkaloids from roots of Rauvolfia ligustrina in the noradrenergic neurotransmission

The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-β-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO 13C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay. Compounds 1, 2 and 9 presented a potent inhibitory effect in the neurotransmission while 3 and 11 showed an acute neuroexcitatory effect. Compound 10 exhibited a very effective post-synaptic inhibitory activity.

Hypoglycemic triterpenoid glycosides from Cyclocarya paliurus (Sweet Tea Tree)

Four new rarely occurred seco-dammarane triterpenoid glycosides (1-4) and four new dammarane triterpenoid glycosides (5-8), along with four known triterpenoids (9-12), were isolated from the 70% ethanol extract of the leaves of Cyclocarya paliurus (family Juglandaceae). Their structures were elucidated by extensive spectroscopic methods, including 1D/2D NMR and HRESIMS data, together with chemical analysis and DFT GIAO 13C NMR calculation. In bioassay, compounds 5-8 significantly increased glucose consumption in 3T3-L1 adipocytes, which could be the bioactive constituents for the anti-diabetes effect of the traditional usage of C. paliurus.

Azaphilones with protein tyrosine phosphatase inhibitory activity isolated from the fungus Aspergillus deflectus

Six undescribed azaphilones, deflectins C1-C3, deflectins D1-D2, and deflectin E, along with five known azaphilones were obtained from a solid culture of the wild fungus Aspergillus deflectus NCC0415. Their structures were determined by HRESIMS, NMR and ECD analyses, together with the GIAO 13C NMR calculation method. All compounds displayed strong or moderate inhibitory activity against protein tyrosine phosphatases SHP2 and PTP1B. Structure-activity relationship analysis of these azaphilones suggested that the length of the ketone aliphatic side chain would affect their SHP2 and PTP1B inhibitory activity. In addition, the presence of a Δ8(12) double bond on γ-lactone ring and the presence of CH3-2’ in fatty chains may increase their inhibitory activity.

Cytotoxic cytochalasans from fungus Xylaria longipes

Five new cytochalasans (1–5) were isolated from the rice fermentation of fungus Xylaria longipes, along with seven known compounds cytochalasin P (6), cytochalasin D (7), zygosporin D (8), 7-O-acetylcytochalasin D (9), cytochalasin C (10), 6,7-dihydro-7-oxo-cytochalasin C (11), and 6,7-dihydro-7-oxo-deacetylcytochalasin C (12). Their structures and absolute configurations were determined by extensive experimental spectroscopic methods as well as ECD calculation and GIAO 13C NMR calculation. The cytotoxicity of obtained compounds (1−12) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Compounds 6–8, 11, and 12 showed cytotoxicity with IC50 value ranging from 4.17–37.18 μM.

Cytochalasins D1 and C1, unique cytochalasans from endophytic fungus Xylaria cf. curta

Cytochalasins D1 (1) and C1 (2) were isolated from the liquid fermentation of fungus Xylaria cf. curta. Their structures and absolute configurations were determined by comprehensive experimental spectroscopic methods as well as ECD and GIAO 13C NMR calculation. They possess a unique eleven-membered macrocycle with an oxygen bridge. Cytochalasins D1 and C1 showed moderate cytotoxicity against human leukemia cell lines HL-60 with IC50 value of 12.7 and 22.3 μM, respectively.

Construction of 6,10-syn- and -anti-2,5-Dioxabicyclo[2.2.1]heptane Skeletons via Oxonium Ion Formation/Fragmentation: Prediction of Structure of (E)-Ocellenyne by NMR Calculation.

A highly efficient and stereoselective route to potential synthetic intermediates for ocellenyne and related C15 acetogenin natural products with 6,10-syn- and 6,10-anti-2,5-dioxabicyclo[2.2.1]heptane core structures has been developed by means of an iterative biogenesis-inspired oxonium ion formation/fragmentation sequence. In accordance with chemical transformations, the most likely stereostructure for (E)-ocellenyne on the basis of GIAO 13C NMR calculations possesses a 6,10-anti-2,5-dioxabicyclo[2.2.1]heptane core, as predicted from a plausible biosynthetic pathway, instead of the spectroscopically proposed 6,10-syn-2,5-dioxabicyclo[2.2.1]heptane skeleton.

Sweriyunnanlactone A, one unusual secoiridoid trimer from Swertia yunnanensis

One unusual secoiridoid trimer, namely sweriyunnanlactone A (1), was isolated from Swertia yunnanensis under the guidance of LC–MS analysis. Sweriyunnanlactone A with a phenyl ring (ring F) was the first example of secoiridoid trimer featuring a C28 skeleton. Its structure was determined by extensive HRESIMS, 1D and 2D NMR spectroscopic data, and GIAO 13C NMR calculation. Compound 1 showed weak inhibition on HBV DNA replication with an IC50 value of 60.76μM (SI=12.6) on HepG 2.2.15 cell line in vitro.

Successful combination of computationally inexpensive GIAO 13C NMR calculations and artificial neural network pattern recognition: a new strategy for simple and rapid detection of structural misassignments

GIAO NMR chemical shift calculations coupled with trained artificial neural networks (ANNs) have been shown to provide a powerful strategy for simple, rapid and reliable identification of structural misassignments of organic compounds using only one set of both computational and experimental data. The geometry optimization, usually the most time-consuming step in the overall procedure, was carried out using computationally inexpensive methods (MM+, AM1 or HF/3-21G) and the NMR shielding constants at the affordable mPW1PW91/6-31G(d) level of theory. As low quality NMR prediction is typically obtained with such protocols, the decision making was foreseen as a problem of pattern recognition. Thus, given a set of statistical parameters computed after correlation between experimental and calculated chemical shifts the classification was done using the knowledge derived from trained ANNs. The training process was carried out with a set of 200 molecules chosen to provide a wide array of chemical functionalities and molecular complexity, and the results were validated with a set of 26 natural products that had been incorrectly assigned along with their 26 revised structures. The high prediction effectiveness observed makes this method a suitable test for rapid identification of structural misassignments, preventing not only the publication of wrong structures but also avoiding the consequences of such a mistake.