Houttuynoid M (1), a new houttuynoid, and the related known compound houttuynoid A (2) were isolated from Houttuynia cordata. Their structures were defined using NMR data analysis, HR-MSn experiment, and chemical derivatization. Houttuynoid M is the first example of a houttuynoid with a bis-houttuynin chain tethered to a flavonoid core. A putative biosynthetic pathway of houttuynoid M (1) is proposed. The anti-herpes simplex virus (anti-HSV) activities of 1 and 2 (IC50 values of 17.72 and 12.42 μM, respectively) were evaluated using a plaque formation assay with acyclovir as the positive control.

Eight new (1a/1b, 2a, 3a, 4a/4b, and 5a/5b) and seven known (2b, 3b, and 6–10) asarone-derived phenylpropanoids, a known asarone-derived lignan (12), and four known lignan analogues (11 and 13–15) were isolated from the rhizome of Acorus tatarinowii Schott. The structures were elucidated via comprehensive spectroscopic analyses, modified Mosher’s method, and quantum chemical calculations. Compounds 1–8 were present as enantiomers, and 1–5 were successfully resolved via chiral-phase HPLC. Compounds 1a/1b were the first cases of asarone-derived phenylpropanoids with an isopropyl C-3 side-chain tethered to a benzene core from nature. Hypoglycemic, antioxidant, and AChE inhibitory activities of 1–15 were assessed by the α-glucosidase inhibitory, ORAC, DPPH radical scavenging, and AChE inhibitory assays, respectively. All compounds except 3a showed α-glucosidase inhibitory activity. Compound 3b has the highest α-glucosidase inhibitory effect with an IC50 of 80.6 μM (positive drug acarbose IC50 of 442.4 μM). In the antioxidant assays, compounds 13–15 exhibited ORAC and DPPH radical scavenging activities. The results of the AChE inhibitory assay indicated that all compounds exhibited weak AChE inhibitory activities.

Dimericbiscognienyne A (1), an unusual diisoprenyl-cyclohexene-type meroterpenoid dimer, was isolated from Biscogniauxia sp. together with three new monomeric diisoprenyl-cyclohexene-type meroterpenoids (2–4) and one new isoprenyl-benzoic acid-type meroterpenoid (5). All structures were determined by extensive NMR spectroscopic methods, quantum chemical calculations, chemical derivatization, and X-ray crystallography. The formation of 1 is related to a unique intermolecular redox coupling Diels–Alder adduct reaction. Their cytotoxicities and short-term memory enhancement activities against Alzheimer’s disease were assessed.

•This research represented a systematic work on wolfberry polyphenols.•53 major polyphenols including 9 new phenylpropanoids and a new coumarin were identified.•22 known polyphenols were the first isolates from the genus Lycium.•Antioxidant and anti-Alzheimer’s disease activities of all polyphenols were evaluated.•Structure–antioxidant activity relationship of phenylpropanoids was proposed.Nine new phenylpropanoids, one new coumarin, and 43 known polyphenols were isolated from wolfberry. Their structures were determined by spectroscopic analyses, chemical methods, and comparison of NMR data. Polyphenols, an important type of natural products, are notable constituents in wolfberry. 53 polyphenols, including 28 phenylpropanoids, four coumarins, eight lignans, five flavonoids, three isoflavonoids, two chlorogenic acid derivatives, and three other constituents, were identified from wolfberry. Lignans and isoflavonoids were firstly reported from wolfberry. 22 known polyphenols were the first isolates from the genus Lycium. This research presents a systematic study on wolfberry polyphenols, including their bioactivities. All these compounds exhibited oxygen radical absorbance capacity (ORAC), and some compounds displayed DPPH radical scavenging activity. One compound had acetylcholinesterase inhibitory activity. The discovery of new polyphenols and their bioactivities is beneficial for understanding the scientific basis of the effects of wolfberry.

A new asarone-derived racemate (1) was isolated from the rhizome of Acorus tatarinowii. The structure of 1 was established by comprehensive spectroscopic analyses, and it was successfully resolved by chiral HPLC, demonstrating that it is racemic. The absolute configurations of 1a [(−)-acortatarone A] and 1b [(+)-acortatarone A] were determined using quantum chemical calculations. Compounds 1a and 1b were the first cases of asarone derivatives with the 5,7-dialkyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one core. The α-glucosidase inhibitory and acetylcholinesterase (AChE) inhibitory activities of 1 were evaluated, and it exhibited α-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).Download high-res image (166KB)Download full-size image

Four interesting sequoiatones stereoisomers (1–4) were isolated from a wetland soil-derived fungus Talaromyces flavus by chiral HPLC. On the basis of comprehensive NMR and mass analyses, their planar structures were elucidated as the same as that of sequoiatone B. Among them, 1 and 3 (or 2 and 4) were a pair of enantiomers, and 1 and 2 (or 3 and 4) were a pair of stereoisomers with epimerization at C-12, which indicated that sequoiatione-type metabolites exist as enantiomers rather than as optically pure compounds in some strains. With the quantum chemical ECD calculations, the absolute configurations of C-8 in 1–4 were determined, which is the first report to establish the absolute configuration of C-8 in sequoiatones. However, the absolute configurations of C-12 in sequoiatones are still unsolved.In our investigation, four stereoisomers of sequoiationes were isolated by chiral HPLC, whose planar structures were the same as that of sequoiatione B. Among them, 1 and 3 (or 2 and 4) are a pair of enantiomers, and 1 and 2 (or 3 and 4) are a pair of stereoisomers with epimerization at C-12, which indicated that sequoiatione-type metabolites exist as enantiomers rather than as optically pure compounds in some strains. Based on the analyses of experimental and quantum chemical ECD, it was found that the absolute configuration of C-8 in sequoiationes can be determined by ECD, which is the first time to discuss the absolute configuration of C-8 in sequoiationes.Download high-res image (103KB)Download full-size image

Fusarins G1/G2 (1/2) and G3/G4 (3/4), two sets of interesting examples of diastereoisomers with substantially identical NMR data, were discovered from natural products. The reason was discussed and the generally applicable determinant conditions were proposed. The minimum interval for stereoclusters to be entirely segregated was also discussed.

Six new 16-membered macrolides with a rare branched octose unit, aldgamycins J–O (1–6), along with two known compounds, swalpamycin B (7) and chalcomycin (8), were isolated from Streptomyces sp. HK-2006-1. Their structures were determined by detailed spectroscopic and X-ray crystallographic analysis. Natural products containing branched sugar units are rare. Aldgaropyranose and decarboxylated aldgaropyranose are branched octoses, specifically aldgarose-type branched octose. Until now, only 11 compounds have been reported to contain an aldgarose-type branched octose. The discovery of aldgamycins J–O (1–6) adds new members of this type of natural product. All the compounds (1–8) herein were tested for antimicrobial activities against Gram-positive Staphylococcus aureus 209P, Gram-negative Escherichia coli ATCC0111, and two fungi, Candida albicans FIM709 and Aspergillus niger R330. Most of these compounds showed antibacterial activity against S. aureus. Their preliminary structure–activity relationships are proposed.

Fifteen new dicaffeoylspermidine derivatives, lycibarbarspermidines A–O (1–15), were isolated from the fruit of Lycium barbarum (wolfberry). The structures were unambiguously determined by spectroscopic analyses and chemical methods. Dicaffeoylspermidine derivatives, a rare kind of plant secondary metabolites, are primarily distributed in the family of Solanaceae. Only six compounds were structurally identified, and all of them are acyclic aglycones. Compounds 1–15 are the first glycosidic products of dicaffeoylspermidine derivatives, and compounds 14–15 are the first cyclization products of dicaffeoylspermidine derivatives. Moreover, dicaffeoylspermidine derivatives were first isolated and identified from wolfberry. The short-term memory assay on a transgenic fly Alzheimer’s disease (AD) model showed that 1–15 exhibited different levels of anti-AD activity. The oxygen radical absorbance capacity assay revealed that 1–15 all displayed antioxidant capacity. Both anti-AD and antioxidant functions are related to the effects of wolfberry. Therefore, dicaffeoylspermidine derivatives are considered beneficial constituents responsible for the antiaging, neuroprotective, anti-AD, and antioxidant effects of wolfberry.

(±)-Quassidines I (1) and J (2), two pairs of new bis-β-carboline alkaloid enantiomers, were isolated from the stems of Picrasma quassioides. Their structures were determined by the analysis of spectroscopic data, including HRESIMS and 2D NMR, and confirmed by single-crystal X-ray diffraction analysis. The racemic mixtures of 1 and 2 were resolved into two pairs of enantiomers, (+)-S-1a and (−)-R-1b and (+)-S-2a and (−)-R-2b, by HPLC using a chiral Daicel IB-3 column, respectively, which represents the first successful example to resolve bis-β-carboline racemic mixtures. The absolute configurations of the two pairs of enantiomers were determined by comparison between the calculated and experimental ECD spectra. The cytotoxicity evaluation revealed that (+)-S-1a and (+)-S-2a showed more potent cytotoxicity against human cervical HeLa and gastric MKN-28 cancer cell lines with IC50 values of 4.03–6.30 μM than their enantiomers with IC50 values of 9.64–12.3 μM; however, the two (+)-S-quassidines showed similar activities to their enantiomers against the mouse melanoma B-16 cancer cell line.

Eight new viridins, nodulisporiviridins A–H (1–8), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1) that was fermented with potato-dextrose broth. The structures were determined using spectroscopic and X-ray crystallographic analysis. Nodulisporiviridins A–D (1–4) are unique viridins with an opened ring A. The Aβ42 aggregation inhibitory activities of 1–8 were evaluated using a thioflavin T (ThT) assay with epigallocatechin gallate (EGCG) as the positive control (EGCG IC50 of 0.5 μM). Nodulisporiviridin G (7) displayed potent inhibitory activity with an IC50 value of 1.2 μM, and the preliminary trend of activity of these viridins as Aβ42 aggregation inhibitors was proposed. The short-term memory assay on an Aβ transgenic drosophila model of Alzheimer’s disease showed that all eight compounds improved the short-term memory capacity, with potencies close to that of the positive control (memantine).

4,5-seco-Probotryenols A–C (1–3), a new type of sesquiterpenoids named seco-probotryane-type sesquiterpenoid, have been obtained from Stachybotrys bisbyi (PYH05-7), along with five new botryane skeleton sesquiterpenoids (4, 5, and 8–10), and two known ones (6 and 7). Their structures were determined by NMR analyses, chemical derivatization, and X-ray crystallography.

Acorus Linnaeus is a genus of perennial herbs distributed from the northern temperate to the subtropical regions, and has been widely used as traditional folk medicine in China and India since ancient times. Phytochemical studies have shown the presence of numerous beneficial compounds, such as phenylpropanoids, lignans, sesquiterpenoids, alkaloids and others. Neuropharmacological studies have revealed that the Acorus rhizome extract and its constituents, particularly α- and β-asarone, possess anticonvulsant, antiepileptic, neuroprotective, memory enhancing, and sedative properties. This review summarises the traditional uses, phytochemistry, and neuropharmacological activities of Acorus Linnaeus.

Four new sesquiterpenoids, sesquiterpenoids A–D (1–4), were isolated from solid cultures of the Xylariaceae fungus (no. 63-19-7-3). Their structures were determined through NMR analyses, CD calculation, the in situ dimolybdenum CD method, the modified Mosher's method, and X-ray data analysis. The cytotoxicities of all compounds against HL-60, SMMC-7721, A-549, MCF-7 and SW480 human cancer cell lines were assayed.

Four novel acoranes (1–4), a new cadinane (5), and a new guaiane (6), together with six known sesquiterpenoids, were isolated from the rhizomes of Acorus tatarinowii. Their structures were established on the basis of extensive spectroscopic analysis. The absolute configurations were determined by single crystal X-ray diffraction, electronic circular dichroism (ECD), CD exciton chirality, and an in situ dimolybdenum CD method. The anti-Alzheimer effects of all isolates were evaluated by acetylcholinesterase (AChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibition assays.

Sporormiellin A (1), the first tetrahydrofuran-fused furochromone with an unprecedented tetracyclic skeleton, has been obtained from the fungal strain Sporormiella minima. The structure with absolute configuration was elucidated by NMR data, X-ray crystallography, and quantum chemical ECD calculations.

Three new 6,6-spiroketal polyketides, streptospirodienoic acids A (1), B (2) and streptospirodienoate A (3), were obtained from the fermentation broth of Streptomycetes sp. (no. 0950134). Their structures were constructed by one 6,6-spiroketal core coupled with hexadienoic acid, in which the starter unit might be 2-methylpropionyl-CoA. Their chemical structures were determined by detailed analyses of UV, IR, HRESIMS, 1D, 2D-NMR spectroscopic data and the X-ray crystallography technique. The biosynthetic pathway for 1 and 2 was proposed. Compound 3 showed moderate cytotoxic activity against HCT-116 cells (IC50 = 5.2 μM), while compounds 1 and 2 showed no activity (IC50 > 10.0 μM).

Five new xanthoquinodins, A4–A6 (1–3), B4 (4), and B5 (5), were isolated from the crude extract of the endolichenic fungal strain Chaetomium elatum (No. 63-10-3-1), along with three known xanthoquinodins, A1–A3 (6–8). Their structures were determined by detailed spectroscopic analysis and comparison of the NMR data with those of the closely related compounds previously reported. The absolute configuration of 1 was established by X-ray crystallographic analysis and ECD calculation. The cytotoxic activity of all compounds was tested against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines.

Xinshengin (1), the first tetracyclic altenusin with an unprecedented altenuene/tetrahydrofuran-fused skeleton core, has been obtained from cultures of an endolichenic fungal strain Phialophora spp. (No. 39-1-5-1), along with a new compound, phialophoriol (2), and a known compound, altenusin (3). The structures with absolute configurations of 1 and 2 were elucidated by analysis of NMR and quantum chemical ECD calculation.

Five new phenethylamine (PEA) derivatives (1–5) were isolated from the strain of Arenibacter nanhaiticus sp. nov. NH36AT derived from the marine sediment of the South China Sea by bioassay-guided fractionation. Their structures were elucidated by spectroscopic methods including UV, IR, HR-MS and NMR. Interestingly, compounds 1–4 existed as enantiomers, which were resolved by chiral liquid chromatography. The resolved configuration of each enantiomer was assigned by the Marfey’s method. Of these compounds, 5 showed weak antimicrobial activity against Staphylococcus aureus and Bacillus subtilis with MIC values of 0.50 and 0.25 mg ml−1, respectively.

Two C18-diterpenoid alkaloids, puberunine (1) and puberudine (2), together with four other new alkaloids, including the first examples having β-oriented substitution at C-3 and a rare chloro-substituent were isolated from Aconitum barbatum var. puberulum. Their structures were elucidated by spectroscopic methods. Puberunine and puberudine, which possess a unique rearranged E ring and an opened A ring, respectively, represent new subtypes of the C18-diterpenoid alkaloids. A plausible biosynthetic pathway of 1 and 2 was proposed.

Houttuynoids A–E (1–5), a new type of flavonoid with houttuynin tethered to hyperoside, and their presumed biosynthetic precursor hyperoside (6) were isolated from the whole plant of Houttuynia cordata. Their structures were elucidated by analysis of 1D and 2D NMR. A hypothetical biogenetic pathway for houttuynoids A–E was proposed. Compounds 1–5 exhibited potent anti-HSV (herpes simplex viruses) activity.

Adeninealkylresorcinol (1), an unusual alkylresorcinol with adenine-alkylresorcinol conjoined skeleton, was isolated from an endophytic fungus Lasiodiplodia sp. obtained from a traditional Chinese medicine Houttuynia cordata Thunb., together with three new biogenetically related compounds (2–4). Their structures were elucidated by comprehensive spectroscopic analysis, and the absolute configuration of 4 was determined by the modified Mosher's method and quantum chemical calculation. Among them, adeninealkylresorcinol (1) is the first alkylresorcinol tethered with nucleobase. In addition, the antioxidant, cytotoxic, and antimicrobial activities of 1–3 were evaluated.Adeninealkylresorcinol (1), the first case of alkylresorcinol tethered with nucleobase, was isolated from an endophytic fungus Lasiodiplodia sp., together with three new biogenetically related compounds (2–4). The antioxidant, cytotoxic, and antimicrobial activities of 1–3 were evaluated and 1–3 showed potent antioxidant activity.Download high-res image (204KB)Download full-size image

Fusarins G1/G2 (1/2) and G3/G4 (3/4), two sets of interesting examples of diastereoisomers with substantially identical NMR data, were discovered from natural products. The reason was discussed and the generally applicable determinant conditions were proposed. The minimum interval for stereoclusters to be entirely segregated was also discussed.