Extensive 2D NMR Research Articles

Phloridzin Highly Accumulated in Malus rockii Rehder and Its Structure Revision and Hypolipidemic Activity.

Phloridzin is a lead compound of the prestigious antidiabetic gliflozins. The present study found that phloridzin highly accumulated in Malus rockii Rehder. The content of phloridzin in M.rockii was the highest among wild plants, with the percentage of 15.54% in the dry leaves. The structure of phloridzin was revised by proton exchange experiments and extensive 2D NMR spectra. Phloridzin exhibited significant hypolipidemic activity in golden Syrian hamsters maybe by increasing the expression of CYP7A1, at the doses of 50 mg/kg and 200 mg/kg. The total performance of anti-hyperlipidemic effect of phloridzin may be superior to that of lovastatin, though lovastatin was more active than phloridzin. In addition, phloridzin exhibited moderate antimalarial activity with inhibition ratio of 31.3 ± 10.9% at a dose of 25 mg/kg/day, and showed moderate analgesic activity with 28.0% inhibition at a dose of 50 mg/kg.

Mono- and Dimeric Xanthones with Anti-Glioma and Anti-Inflammatory Activities from the Ascidian-Derived Fungus Diaporthe sp. SYSU-MS4722.

Seven new xanthones, diaporthones A−G (1−7), together with 13 known analogues, including five mono- (8−14) and six dimeric xanthones (15−20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HR-ESIMS). The absolute configurations of 1−7 were clearly identified by X-ray crystallographic analysis and calculation of the ECD Spectra. Compounds 15−20 showed significant anti-inflammatory activity with IC50 values between 6.3 and 8.0 μM. In addition, dimeric xanthones (15−20) showed selective cytotoxicity against T98G cell lines with IC50 values ranging from 19.5 to 78.0 μM.

Triterpenoids from Uncaria rhynchophylla and Their PTP1B Inhibitory Activity

Uncaria rhynchophylla (Gouteng) is a famous traditional Chinese medicine used for psychiatric and hypotensive purposes in China. In this study, the ethyl acetate (EtOAc) part of U. rhynchophylla was revealed with protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Subsequent investigation on the EtOAc part yielded one new triterpenoid, 3β-formyloxy-6β,19α-dihydroxyurs-12-en-28-oic acid (1) and four known ones, 3β,6β,19α-trihydroxyurs-12-en-28-oic acid (2), 2-oxopomolic acid (3), 3β,19α-dihydroxy-6-oxo-olean-12-en-28-oic acid (4) and sumaresinolic acid (5). The structure of compound 1 was determined by extensive HRESIMS, IR, 1D and 2D NMR spectroscopic analyses. Two ursane-type triterpenoids (2 and 3) showed selective inhibition on PTP1B with IC50 values of 48.2 and 178.7 μM. The enzyme kinetic study suggested that compounds 2 and 3 were mix-type inhibitors on PTP1B with Ki values of 15.6 and 132.5 μM. This investigation manifests the antidiabetic potency of U. rhynchophylla with triterpenoids as the active constituents.

Structurally diverse biflavonoids from Dysosma versipellis and their bioactivity.

Five pairs of new biflavonoid enantiomers, (±)-dysosmabiflavonoids A-E (1-5), two new biflavonoids, dysosmabiflavonoids F-G (6-7), and four biosynthetically related precursors (8-11) were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by extensive spectroscopic analysis, including HR-ESI-MS and 2D NMR. Their absolute configurations were determined by comparison of the calculated and experimental ECD spectra. All isolated compounds were evaluated for AChE inhibitory activity. Compounds 6 and 7 exhibited more potent inhibitory activities with IC50 values of 1.42 and 0.73 µM, respectively, than their biosynthetically related precursors kaempferol (8, 17.90 µM) and quercetin (9, 3.96 µM). The preliminary structure-activity relationship study indicated that the connection mode of biflavonoid subunits, oxidation degree of the C ring, and 3,4-dihydroxy group of the B ring were important structural factors for AChE inhibitory activity. Racemates 1-5 and their corresponding levorotatory and dextrorotatory enantiomers were tested for their potential to impede the generation of NO in lipopolysaccharide-stimulated RAW264.7 cells, and their mushroom tyrosinase inhibitory effect. Racemate 1 displayed more potent mushroom tyrosinase inhibitory activity (IC50, 28.27 µM) than the positive control kojic acid (IC50, 32.59 µM). D. versipellis may have therapeutic potential for melanogenesis disorders and neurodegenerative diseases.

Further report on the chemical constituents of the n-hexane extract of Leonotis nepetaefolia (L.) R. Br (Lamiaceae)

Introduction: Leonotis nepetifolia (L.) R. Br, a species of the family Lamiaceae, has some interesting biological activities, such as antibacterial, antioxidant, and anti-inflammatory activities. This paper describes the structural elucidation of seven compounds isolated from Leonotis nepetifolia collected in Xuyen Moc district, Ba Ria–Vung Tau Province, in June 2018. Methods: Phytochemical investigations of the n-hexane extract of Leonotis nepetifolia led to the isolation of seven pure compounds. Their chemical structures were elucidated by extensive MS, 1D and 2D-NMR spectroscopic analysis and comparison with previously published data. Results: Seven compounds, namely, (E)-10-oxooctadeca-8-enoic acid (1), ergosterol peroxide (2), turmeronol A (3), methyl (E)-3-(3,4-dimethoxyphenyl)propenoate (4), methyl 4-hydroxybenzoate (5), methyl (E)-3-(4-hydroxy-3-methoxyphenyl)propenoate (6), and alpinumisoflavone (7), were identified. Conclusions: Although these compounds are known in other species, this is the first time they have been reported in Leonotis nepetifolia.

Structure Revision and Protein Tyrosine Phosphatase Inhibitory Activity of Drazepinone.

From the marine-derived fungus Penicillium sumatrense (Trichocomaceae), a pair of enantiomers [(+)-1 and (−)-1] were isolated with identical 1D NMR data to drazepinone, which was originally reported to have a trisubstituted naphthofuroazepinone skeleton. In this study, we confirmed the structures of the two enantiomers as drazepinone and revised their structures by detailed analysis of extensive 2D NMR data and a comparison of the calculated 13C chemical shifts, ECD, VCD, and ORD spectra with those of the experiment ones. (+)-1 and (−)-1 were evaluated for their PTP inhibitory activity in vitro. (−)-1 showed selective PTP inhibitory activity against PTP1B and TCPTP with IC50 values of 1.56 and 12.5 μg/mL, respectively.

New cyclic diarylheptanoids from the false heartwood of Betula pubescens Ehrh

Two undescribed (1–2) and five known cyclic diarylheptanoids (3–7) were isolated from the false heartwood of white birch (Betula pubescens Ehrh.). All structures were elucidated through extensive 1D and 2D NMR experiments and HR-ESI-MS data, along with comparison of their spectroscopic data with those reported in the literature. The two new cyclic diarylheptanoids are betuladiol (1) and betulondiol (2). Extracts from false heartwood were evaluated for their antimicrobial activity against Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Staphylococcus aureus and Cutibacterium acnes together with their antifungal activity against Candida albicans and Candida glabrata.

Neo-Clerodane Diterpenoids from the Aerial Parts of Scutellaria barbata with Anti-Inflammatory Activity.

The bioactivity-guided isolation on the Scutellaria barbata extract resulted in the purification of four undescribed neo-clerodane diterpenoids, scuttenlines A-D (1-4), alone with 20 known diterpenoids (5-24). The chemical structures of them were elaborated by extensive spectroscopic means, including 1D, 2D-NMR and HR-MS. The anti-inflammatory potential ability of 1-24 was screened in lipopolysaccharide-stimulated mouse RAW 264.7 cells. Scuttenline C (IC50 =1.9 μM) and 18 (IC50 =3.7 μM) exhibited potent activity to inhibit NO production.

Multioxidized aromatic polyketides produced by a soil-derived fungus Penicillium canescens

Under OSMAC strategy, seven unreported multioxidized aromatic polyketides, penicanesins A‒G, were discovered from a soil-derived fungus Penicillium canescens along with seven known compounds. Their structures were assigned by extensive 1D and 2D NMR spectra in combination with HRESIMS and single crystal X-ray diffraction. Absolute stereochemistry of penicanesins A and D were elucidated by theoretical ECD calculation. (±)-Penicanesins A and B are two pairs of racemic aromatic polyketides with an unusual 6/6/6/6 heterotetracyclic ring core. In bioassay, (−)-penicanesin A shows potential cytotoxicity against human cancer cell lines HL-60 and SW480 with IC50 values at 13.8 ± 0.6 and 12.5 ± 0.9 μM, respectively, whereas the enantiomer (+)-penicanesin A is less active.

Two new dihydroisocoumarins and terpenoids from Scorzonera longiana Sümbül an endemic species to Turkey and their antimicrobial activity

Two new dihydroisocoumarins (scorzolongin I (1), and scorzolongin II (2)) and nine known compounds (3′,5′-dimethoxy hydrangenol (scorzolongin III, 3), cladantholide (4), dammar-24-ene-3β-ol (5), taraxasterol (6), β-sitosterol (7), mangifgerursanone (8), and a mixture of α-amyrenone (9a), β-amyrenone (9b), and dammar-24-ene-3-one (9c) in about 1:1:2 ratio) were identified from the dichloromethane fraction of Scorzonera longiana. The structure of all compounds (1–9a–c) were elucidated by extensive 1D and 2D NMR (1H, 13C/APT, COSY, HMBC, HSQC, and NOESY) spectroscopy, UV, FT-IR, and LC-QTOF-MS data and by comparison of their NMR data with the literature. These compounds have been isolated from S. longiana for the first time. An antimicrobial assay against eight microorganisms was applied to isolated compounds 1–3. Scorzolongin I, and scorzolongin II, and scorzolongin III showed notable activity against gram (-) (Escherichia coli and Yersinia pseudotuberculosis) and fungi (Candida albicans, Saccharomyces cerevisiae) with 20 mm inhibition zone each. Scorzolongin II (2) exhibited strong activity against E. coli, Y. pseudotuberculosis, Mycobacterium smegmatis C. albicans, S. cerevisiae with MIC value of 33.8 μg/mL.

Japonisine A, a fawcettimine-type Lycopodium alkaloid with an unusual skeleton from Lycopodium japonicum Thunb

Japonisine A, a novel fawcettimine-type Lycopodium alkaloid with an unusual skeleton and two new fawcettimine-type ones, along with 20 known Lycopodium alkaloids, were isolated from the whole plants of Lycopodium japonicum Thunb. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, as well as by comparison with the literature data. Notably, japonisine A (1) was the first example of fawcettimine-related Lycopodium alkaloid with a 2-oxopropyl attached at C-6. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and α-glucosidase. Unfortunately, the results indicated that all the compounds were inactive against the acetylcholinesterase (AChE) and α-glucosidase.

Bhimamycin J, a Rare Benzo[f]isoindole-dione Alkaloid from the Marine-Derived Actinomycete Streptomyces sp. MS180069.

Chemical investigation on a Streptomyces sp. strain MS180069 isolated from a sediment sample collected from the South China Sea, yielded the new benzo[f]isoindole-dione alkaloid, bhimamycin J (1). The structure was determined by extensive spectroscopic analysis, including HRMS, 1D, 2D NMR, and X-ray diffraction techniques. A molecular docking study revealed 1 as a new molecular motif that binds with human angiotensin converting enzyme2 (ACE2), recently described as the cell surface receptor responsible for uptake of 2019-CoV-2. Using enzyme assays we confirm that 1 inhibits human ACE2 79.7 % at 25 μg/mL.

Three new steroidal sapogenins derived from the roots of Cynanchum otophyllum and their cytotoxic activities

Three new steroidal sapogenins, 3β,8β,14β-trihydroxycarda-5,20(22)-dienolide (1), (20R)-12β,20-epoxy-3β,8β,14β-trihydroxy-17α-pregn-5-en-17-yl 4-hydroxy-3-methoxybenzoate (2), and 3,20-dioxo-8β,14β,17β-trihydroxy-17α-pregn-5-en-12β-yl 4-hydroxybenzoate (3), along with four known C21-steroidal sapogenins (4-7) were isolated from the hydrolysate of Cynanchum otophyllum roots. Among them, compound 1 harbouring a rare β-OH at the C-8 position in the cardenolide skeleton, was identified for the first time in the genus Cynanchum. Their structures were elucidated via extensive spectroscopic analysis, including UV, IR, HR-ESI-MS, 1D and 2D NMR. Compounds 1-7 were evaluated for their cytotoxic activities against four cancer cell lines (MCF-7, H1299, HeLa, and HepG2). Compound 1 exhibited significant inhibitory effects on the growth of the four cell lines, exhibiting IC50 values ranging from 6.86 to 22.09 μM.

Cladamide: a new ceramide from the endophytic fungus Cladosporium cladosporioides

A new ceramide, named cladamide (1), in addition to cinnamic acid (2), para-coumaric acid (3), stigmasterol-3-O-β-D-glucoside (4), and uracil (5), was isolated from the white beans culture of Cladosporium cladosporioides, a marine-derived endohpytic fungus isolated from the leaves of the mangrove, Avicennia marina (Forssk.) Vierh. Structure elucidation of compound 1 was established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with HR-ESI-MS. The ability of the isolated compounds to inhibit acetylcholine esterase was evaluated. Compound 3 showed the highest acetylcholine esterase inhibitory activity (IC50 = 0.057 ± 0.003 µM), followed by compound 4 (IC50 = 0.068 ± 0.003 µM) and compound 1 (IC50 = 0.099 ± 0.005 µM) compared to donepezil, the positive control, (IC50 = 0.044 ± 0.002 µM). Compounds 2 and 5 showed lower activity (IC50 = 0.182 ± 0.009 and 0.236 ± 0.012 µM, respectively). The results were further validated by molecular docking study.

Withanolide-Type Steroids from Physalis nicandroides Inhibit HIV Transcription.

The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A–D (1–4), together with nine related known compounds (5–13) isolated from the aerial parts of Physalis nicandroides. Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs. Their biological evaluation as inhibitors of human immunodeficiency virus type 1 replication revealed that two compounds from this series, 7 and 13, displayed strong inhibition of HIV-1 replication with IC50 values lower than 2 μM. Moreover, cellular mechanism experiments showed that the main target of these compounds in the HIV replication cycle is viral transcription. This study is the first report of withanolide-type steroids as HIV inhibitors and provides insight into their potential as candidates for further preclinical studies.

Isolation of Sesquiterpenoids and Steroids from the Soft Coral Sinularia brassica and Determination of Their Absolute Configuration.

Two undescribed rearranged cadinane-type sesquiterpenoids (1–2), named sinulaketol A-B, together with one new chlorinated steroid (3), one new gorgosterol (4), one known sesquiterpene (5), one known dibromoditerpene (6) and two known polyhydroxylated steroids (7–8) were isolated from the soft coral Sinularia brassica. The structures of these compounds were established by extensive spectroscopic analysis, including HRESIMS, 1D, and 2D NMR spectroscopy. Their absolute configurations were also determined by the ECD calculations and DP4+ probability analysis. Antileishmanial activity of compounds 1–8 was evaluated in vitro against the amastigote forms of Leishmania donovani, in which compounds 3, 6, and 7 inhibited the growth of L. donovani by 58.7, 74.3, 54.7%, respectively, at a concentration of 50 μM. Antimicrobial effect of the isolated compounds were also evaluated against Candida albicans, Staphylococcus aureus, and Escherichia coli. Compound 6, a brominated diterpene, exhibited antimicrobial effect against S. aureus.

Six New 3,5-Dimethylcoumarins from Chelonopsis praecox, Chelonopsis odontochila and Chelonopsis pseudobracteata

Ten 3,5-dimethylcoumarins (1–6 and 8‒11) involving six new ones (1–6), together with a known 3-methylcoumarin (7), were isolated from the aerial parts of three Chelonopsis plants, C. praecox, C. odontochila, and C. pseudobracteata. The structures of the new compounds were determined by extensive HRESIMS, 1D and 2D NMR spectroscopic analyses. According to the substitution at C-5, these coumarins were classified into 5-methyl, 5-hydroxymethyl, 5-formyl, and 5-nor types. All the isolates were assayed for their inhibition on α-glucosidase, protein tyrosine phosphatase 1B, and T-cell protein tyrosine phosphatase in vitro.Graphic

A New Cytotoxic Evodiamine Derivative From Tetradium ruticarpum (A. Jussieu) T. G. Hartley

1-Hydroxymethyl goshuyuamide II (1), a new derivative of evodiamine with a quinazolinocarboline skeleton, along with nine known evodiamine derivatives were isolated from the dried and nearly ripe fruits of Tetradium ruticarpum (A. Jussieu) T. G. Hartley using several different chromatographic separations. Their structures were elucidated on the basis of extensive spectroscopic techniques, including 1D and 2D NMR spectra. Putative biosynthetic pathways toward 1 are proposed. Compounds 1 and 2 and 4 to 10 exhibited cytotoxic activity against six human tumor lines, and compounds 4 and 7 to 10 exhibited moderate inhibitory activity against nitric oxide production in LPS-activated RAW264.7 cells.

Dual High-Resolution α-Glucosidase and PTP1B Inhibition Profiling Combined with HPLC-PDA-HRMS-SPE-NMR Analysis for the Identification of Potentially Antidiabetic Chromene Meroterpenoids from Rhododendron capitatum.

Thirteen previously undescribed chromene meroterpenoids, capitachromenic acids A-M (3-6, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b, and 11b), were identified from an ethyl acetate extract of Rhododendron capitatum, using dual high-resolution α-glucosidase and PTP1B inhibition profiling in combination with HPLC-PDA-HRMS-SPE-NMR. In addition, one known chromene meroterpenoid, daurichromenic acid (15), and its biosynthetic precursor, grifolic acid (12), two C-methylated flavanones, (2S)-5,7,4'-trihydroxy-8-methylflavanone (1) and farrerol (2), and two triterpenoids, oleanolic acid (14a) and ursolic acid (14b), were identified. New structures were elucidated by extensive 1D and 2D NMR analysis, and absolute configurations of new chromene meroterpenoids were assigned by analysis of their ECD spectra on the basis of the empirical chromane helicity rule and from Rh2(OCOCF3)4-induced ECD spectra by applying the bulkiness rule. Compounds 5, 9a, 9b, 12, and 15 showed α-glucosidase inhibitory activity with IC50 values ranging from 8.0 to 93.5 μM, while compounds 3, 5, 8b, 9a, 9b, 10b, 11b, 12, and 15 showed PTP1B inhibitory activity with IC50 values ranging from 2.5 to 68.1 μM.

Isoprenoid pterocarpans, isoflavonoids and flavonoids from Erythrina stricta

• Three new isoprenoid pterocarpans, erystrictins A-C, were isolated from Erythrina stricta . • Alkaloid 22 was isolated from Erythrina genus for the first time. • Several compounds exhibited certain degrees of cytotoxic activity. A pair of diastereoisomeric pterocarpans, erystrictins A/B (1a/1b), possessing a highly oxidized 3-hydroxy-2-(1-hydroxy-1-methylethyl)- 2,3-dihydro furan substituent, and erystrictin C (2), along with seven known pterocarpans ( 3 - 9 ), eleven known flavonoids ( 10 - 20 ), and two known alkaloids ( 21 - 22 ) were isolated from Erythrina stricta. Their structures were established by extensive spectroscopic analyses, including HRESIMS, 1D and 2D NMR, and electronic circular dichroism (ECD) calculations. Using the MTS method, compounds 1 - 12 were tested for their cytotoxicity against the HL-60, SMMC-7721, A-549, MCF-7 and SW-480 human tumor cell lines, compounds 4, 10 and 12 showed moderated cytotoxicity. All the compounds, except for 10 and 12 were isolated from this plant for the first time. Compound 21 was isolated from Erythrina genus for the first time.