Chemical constituents from Cynanchum paniculatum (Bunge) Kitag

Twenty-nine compounds, including five acetophenone derivatives (1–5), three phenanthroindolizidine alkaloids (12–14), seven pentacyclic triterpenoids (15–21) and five C₂₁ steroidal sapogenins (22–26), were isolated from the root of Cynanchum paniculatum (Bunge) Kitag. Their structures were determined by spectroscopic methods and comparison with reported data. Moreover, the chemotaxonomic relationships were also discussed. As a result, acetophenone derivatives, pentacyclic triterpenoids and C₂₁ pregnane sapogenins can be recognized as chemotaxonomic markers for Cynanchum genus, and C. paniculatum has close relationships with some species of genus Cynanchum.     

Four novel geminally dialkylated,non-aromatic acetophenone derivatives from Melicope coodeana

Four novel geminally dialkylated, non-aromatic acetophenone derivatives 1–4 were isolated from Melicope coodeana. The compounds, related to hop bitter acids, were named Coodeanones A–C, where Coodeanone B was found in both E and Z configuration of the 6′?–7′? double bond. Antibacterial, antifungal and antimalarial activities of the acetophenone derivaties were investigated, and Coodeanone C (4) was found to have activity toward Plasmodium falciparum (malaria) (IC₅₀ = 42.8 μM).     

Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents

Novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 5/6 (pyrazolic chalcones) were synthesized from a Claisen–Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with several acetophenone derivatives 1. Subsequently, the microwave-assisted cyclocondensation reaction of chalcones 5/6 with hydrazine afforded the new racemic 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazoles 7 or their N-acetyl derivatives 8 and 9 when reactions where carried out in DMF or acetic acid, respectively. Several of these compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where 5c and 9g showed remarkable activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI₅₀ values ranging from 0.04 to 11.4 μM, from the in vitro assays.     

Novel γ-lactone derivatives from Trigonostemon heterophyllus with their potential antiproliferative activities

Two novel γ-lactone derivatives, trigoheterophines A (1) and B (2), together with four known furan derivatives (3–6), were isolated from the stems and leaves of Trigonostemon heterophyllus. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparing with the data reported in literature. Among them, trigoheterophines A (1) and B (2) represent an unusual type of γ-lactone derivatives, possessing 21 carbon atoms on the carbon skeleton, and known compouds (3–6) are rare furan derivatives in the plant kingdom with diverse long-chain hydrocarbyl groups as substituents at C-4. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–6 showed significant antiproliferative effects against various human cancer cell lines with IC₅₀ values ranging from 0.28 to 12.06 μM. These findings suggest that the discoveries of these novel γ-lactone derivatives and furan derivatives with significant antiproliferative activities isolated from T. heterophyllus could be of great importance to the development of new anticancer agents.     

Novel tetrahydrofuran derivatives from Trigonostemon howii with their potential anti-HIV-1 activities

A novel tetrahydrofuran derivative, trigonohowine (1), together with five known tetrahydrofuran derivatives (2–6), were isolated from the stems and leaves of Trigonostemon howii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. Among them, trigonohowine (1) represents the first example of a new type of tetrahydrofuran derivative, possessing an unprecedented carbon skeleton containing 23 carbon atoms on the carbon skeleton and the known compouds (2–6) are rare tetrahydrofuran derivatives in the plant kingdom with various carbon skeletons. All isolated compounds were evaluated for their anti-HIV-1 activities. Compounds 1–6 showed significant anti-HIV-1 activities with EC₅₀ ranged from 0.08 to 1.03 µM. These findings suggest that the discoveries of these tetrahydrofuran derivatives with significant anti-HIV-1 activities isolated from T. howii could be of great importance to the development of new anti-HIV agents.     

(±)-Meliviticines A and B: Rearranged prenylated acetophenone derivatives from Melicope viticina and their antimicrobial activity

Two new prenylated acetophenone derivatives racemates, meliviticines A (1) and B (2) with unprecedented rearranged skeletons, were isolated from Melicope viticina. Subsequent chiral resolution led to the separation of two pairs of enantiomers, (±)-meliviticines A (1a/1b) and (±)-meliviticines B (2a/2b). Their structures including absolute configurations were elucidated by extensive spectroscopic data, electronic circular dichroism analysis, and X-ray crystallography. A plausible biosynthetic pathway of 1 and 2, involving ring cleavage and rearrangement of the prenylated acetophenone backbone was proposed. All the isolates showed moderate antimicrobial activities with MIC values of 25–50 μg/mL against several bacterial and fungal strains.     

Preparation of acetylenic sugar derivatives by way of 2-(N-nitroso)acetamido sugars

N-Nitrosation with dinitrogen tetraoxide was used to convert 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-glucopyranose (1) and 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-galactopyranose (4) in high yield into the N-nitroso derivatives 2 and 5, respectively. Similarly, 3-acetamido-1,2,4,6-tetra-O-acetyl-3-deoxy-β-D-glucopyranose (12) and methyl 2-acetamido-3,4,5,6-tetra-O-acetyl-2-deoxy-D-gluconate (15) gave their respective, crystalline N-nitroso derivatives 13 and 16. Various other 2-acetamido sugar derivatives were likewise nitrosated. In ethereal solution, compounds 2 and 16 reacted with potassium hydroxide in isopropyl alcohol to give the C₅ acetylene, 1,2-dideoxy-D-erythro-pent-1-ynitol, isolated as the known triacetate 3. By the same procedure, the galacto derivative 5 was converted in high yield into the 3-epimeric C₅ acetylene, 1,2-dideoxy-D-threo-pent-1-ynitol, isolated as its triacetate 6 and characterized by conversion into the known, crystalline 1,2-dideoxy-3-O-(3,5-dinitrobenzoyl)-4,5-O-isopropylidene-D-threo-pent-1-ynitol (7).     

Cytotoxic xanthene derivatives from Homalium paniculiflorum

Two new xanthene derivatives, homapanicones A (1) and B (2), along with 11 known compounds (3–13), were isolated from the stems of Homalium paniculiflorum. Among them, homapanicones A (1) and B (2) represent the first example of naturally occurring xanthene derivatives with an oxidized aromatic B unit, and the known compounds (3–13) were isolated from this plant for the first time. These structures were established on the basis of extensive spectroscopic methods. Compounds 1 and 2 were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines. Homapanicones A (1) and B (2) showed cytotoxicities against various human cancer cell lines in the range of IC₅₀ at 4.08–24.14 μM.     

trans- and cis-Ru(II) aminophosphine complexes: Syntheses, X-ray structures and catalytic activity in transfer hydrogenation of acetophenone derivatives

The ability of transition metal catalysts to add or remove hydrogen from organic substrates by transfer hydrogenation process is a valuable synthetic tool. For this aim, a novel Ru(II) complex with the P-N ligand [(Ph₂P)₂NCH₂-C₄H₃S] derived from thiophene-2-methylamine was synthesized starting with the complex [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂ and isolated in two isomeric forms: trans- and cis-[Ru((PPh₂)₂NCH₂-C₄H₃S)₂Cl₂], 2 and 3, respectively. The structures of both isomers were also determined by single crystal X-ray diffraction. The cis-isomer 3 can be isolated from the solution of major trans-isomer 2 as yellow crystals. However, upon dissolution 3 is rapidly converted to the trans-isomer 2. The new ruthenium(II) complex provides high catalytic activity in the transfer hydrogenation of acetophenone derivatives to 1-phenylethanol derivatives in the presence of 2-propanol as the hydrogen source. This transfer hydrogenation is characterized by low reversibility under the experimental conditions.     

Synthesis and structure of chloro(ligand)bis(diphenylglyoximato)cobalt(III) complexes

The synthesis and characterization of trans-chloro- (ligand)bis(diphenylglyoximato)cobalt(III) complexes [ligand = pyridine (py), α-, β-, or γ-picoline (α-pic, β-pic, γ-pic), 3,5-lutidine (lut), p-toluidine (p-tol) and PPh₃] is presented. X-ray crystal structure determination of the pyridine (1) and p-toluidine (6) derivatives has been carried out. Compound 1 crystallizes in the monoclinic system, space group P2₁/n, with Z = 4 and unit cell parameters a = 23.124(4), b = 13.009(3) and c = 11.204(3) Å, and β= 93.14(2)°. Compound 6 crystallizes in the monoclinic system, space group P2₁/n, with Z = 4 and unit cell parameters a = 18.792(3), b = 12.540(2) and c = 15.346(3) Å, and β = 97.54(2)°.     

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5–8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC₅₀ value of 15.41?μM.     

Bioactive cytosporone derivatives isolated from the mangrove-derived fungus Dothiorella sp. ML002

Three new cytosporone derivatives dothiorelones K–M (1, 2 and 7), together with six known ones (3–6, 8 and 9) were isolated from the mangrove-derived fungus Dothiorella sp. ML002. Their structures were determined by comprehensive 1D, 2D NMR spectroscopic and HR-ESI-MS spectroscopic data. Compounds 1, 2 and 5 displayed inhibitory activities against α-glucosidase with the IC₅₀ values of 22.0, 77.9 and 5.4 μg/mL, respectively. Additionally, compounds 1, 2, and 5 also exhibited antibacterial activities against Staphylococcus aureus (ATCC 6538) with the same MIC values of 50 μg/mL, respectively. The results indicated that cytosporone derivatives will be useful to as diabetes control agents.     

Three new phenolic glycosides from the whole plant of Aconitum tanguticum (Maxim.) Stapf

Three new phenolic glycosides 2-(3-O-β-d-glucopyranosyl-4-hydroxyphenyl) ethanol 1-O-β-d-glucopyranoside (1), 2-(4-O-β-d-fructopyranosylphenyl) ethanol 1-O-β-d-galactopyranoside (2) and 3-methoxy-4-O-β-d-allopyranosyl acetophenone (3), along with nine known compounds (4–12), were isolated from the ethanol extract of the whole plant of Aconitum tanguticum (Maxim.) Stapf. Their structures were elucidated by analysis of spectroscopic data including 1D-, 2D-NMR and HRESIMS, and the reported literature data comparison. All the compounds were evaluated for their potential anti-inflammatory effects by the inhibition of TNF-α production on LPS-stimulated RAW264.7 macrophages. Compounds 1, 3, 5 and 7–9 showed certain inhibition activity and their IC₅₀ values were 38.18, 27.64, 3.25, 84.45, 12.76 and 18.44 μg/mL, respectively.     

Bioactivity-guided isolation of chemical constituents against H2O2-induced neurotoxicity on PC12 from Cimicifuga dahurica (Turcz.) Maxim.

Three new compounds (1, 6, 9), with six known compounds (2–5, 7–8) were obtained from water-soluble extract of Cimicifuga dahurica (Turcz.) Maxim. by bioactivity-guided isolation. Their structures were elucidated by chemical and spectral analysis, including 1D, 2D NMR data and HRESIMS. H₂O₂-induced neurotoxicity on PC12 cells model were conducted to evaluate the neuro-protective capability of these compounds. The piscidic acid derivatives compounds 4–7 showed marked neuro-protective effect at certain concentration.     

Dibrefeldins A and B,A pair of epimers representing the first brefeldin A dimers with cytotoxic activities from Penicillium janthinellum

Dibrefeldins A and B (1 and 2), two unexpected brefeldin A (BFA) dimers, as well as brefeldin F (3), brefeldin G (4), and 14-hydroxy-BFA (5), three new BFA derivatives, together with three new naturally occurring BFA derivatives (6–8) and four known analogues (9–12), were isolated from the fungus Penicillium janthinellum. Dibrefeldins A and B (1 and 2) represent the first examples of BFA dimers formed by an esterification between two BFA monomer units. Brefeldin F (3) has an α,β-unsaturated γ-lactone ring, and this moiety was first discovered in naturally occurring BFA derivatives. The structures and relative/absolute configurations of these derivatives were elucidated by extensive spectroscopic methods, ¹³C NMR calculations, and single-crystal X-ray diffraction. Compounds 1, 2, 8, and 9 showed excellent cytotoxic activities against six cancer cell lines with IC₅₀ values ranging from 0.01 to 4.45 μM.     

Novel N-oxide derivatives of benzyltetrahydroisoquinoline alkaloid from the tubers of Stephania viridiflavens H.S. Lo et M. Yang

An investigation on the phytochemistry of the medicinal plant Stephania viridiflavens H.S. Lo et M. Yang led to isolate two new naturally occurring benzyltetrahydroisoquinoline alkaloids, (+)-1S, 2R-laudanidine-N_β-oxide 2 and (+)-1S, 2S-laudanidine-N_α-oxide 3, along with four known benzyltetrahydroisoquinoline alkaloids: (+)-laudanidine 1, (+)-reticuline 4, (+)-1S, 2R-reticuline-N_β-oxide 5 and (+)-1S, 2S-reticuline-N_α-oxide 6. The structure and the stereochemistry of these compounds were determined on the basis of spectroscopic methods and also confirmed by partial synthesis. To examine putative acetycholinesterase (AChE) inhibitory or cytotoxic activities, various bioassays were performed, the N-oxide derivatives (5 and 6) demonstrated more potent cytotoxicity than the corresponding free base.     

Stachybotrysams A–E,prenylated isoindolinone derivatives with anti-HIV activity from the fungus Stachybotrys chartarum

Four new farnesylated isoindolinone derivatives, named stachybotrysams A–D (2–5), and one new farnesyl-cyclized analogue, named stachybotrysam E (6), as well as one known congener (1), were isolated from the filamentous fungus Stachybotrys chartarum CGMCC 3.5365. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and by comparison with reported data. Compounds 2–4 exhibited significant HIV-inhibitory activity with IC₅₀ values of 9.3, 1.0, and 9.6 μM, respectively.     

Lactones from the pericarps of Litsea japonica and their anti-inflammatory activities

Five new lactones, litsenolide F₁ (1), lisealactone H₁ (10), lisealactone H₂ (11), akolactone D (13), and akolactone E (14), along with thirteen known compounds were isolated from the pericarps of Litsea japonica (Thunb.) Jussieu. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, HRMS, and chemical methods. The isolated compounds were evaluated for their inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, 2-alkylidene-3-hydroxy-4-methylbutanolide derivatives (compounds 1–9) exhibited the most potent activity, with IC₅₀ values in the range of 2.9–12.8?μM. In additon, compounds 1, 3, 4, and 6 showed inhibition of iNOS and COX-2 expression in concentration-dependent manner. Compound 3 suppresses mRNA expression of iNOS, COX-2, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells. Based on these evidence, the isolated lactones from L. japonica could be promissing candidates for the development of new anti-inflammatory agents.     

Development of acetophenone ligands as potential neuroimaging agents for cholinesterases

Association of cholinesterase with β-amyloid plaques and tau neurofibrillary tangles in Alzheimer’s disease offers an opportunity to detect disease pathology during life. Achieving this requires development of radiolabelled cholinesterase ligands with high enzyme affinity. Various fluorinated acetophenone derivatives bind to acetylcholinesterase with high affinity, including 2,2,2-trifluoro-1-(3-dimethylaminophenyl)ethanone (1) and 1-(3-tert-butylphenyl)-2,2,2-trifluoroethanone (2). Such compounds also offer potential for incorporation of radioactive fluorine (¹⁸F) for Positron Emission Tomography (PET) imaging of cholinesterases in association with Alzheimer’s disease pathology in the living brain. Here we describe the synthesis of two meta-substituted chlorodifluoroacetophenones using a Weinreb amide strategy and their rapid conversion to the corresponding trifluoro derivatives through nucleophilic substitution by fluoride ion, in a reaction amenable to incorporating ¹⁸F for PET imaging. In vitro kinetic analysis indicates tight binding of the trifluoro derivatives to cholinesterases. Compound 1 has a K_i value of 7 nM for acetylcholinesterase and 1300 nM for butyrylcholinesterase while for compound 2 these values are 0.4 nM and 26 nM, respectively. Tight binding of these compounds to cholinesterase encourages their development for PET imaging detection of cholinesterase associated with Alzheimer’s disease pathology.     

Hydrogenolysis of benzylidene acetals of 1,6-anhydro-β-d-galactopyranose derivatives with the LiAlH4—AlCl3 reagent

Benzylidenation of 1,6-anhydro-β-d-galactopyranose (1) and its 2-O-acetyl (2) and 2-O-allyl (3) derivatives under various conditions afforded mixtures of 1,6-anhydro-exo- and -endo-3,4-O-benzylidene-β-d-galactopyranose (4 and 5) and the2-O-acetyl (6 and 7) and 2-O-allyl (8 and 9) derivatives, respectively. Hydrogenolysis of the exo (4 and 8) or the endo (5 and 9) derivatives with the LiAlH₂—AlCl₃ reagent gave only the 3-O-benzyl derivatives (10 and 11).