Degraded diterpenoids from the stem bark of Neoboutonia mannii

Neoboutomannin (1), a degraded diterpenoid dimer, and manniorthoquinone (2), another degraded diterpenoid, have been isolated from the stem bark of Neoboutonia mannii Benth (Euphorbiaceae), together with the known 3-acetylaleuritolic acid (3), 3,6-dihydroxy-9-methoxy-1,7-dimethylphenanthrene (4) and sitosterol 3-O-β-d-glucopyranoside (5). Their structures were elucidated on the basis of spectral studies and comparison with published data. Compounds 1, 3, 4 and 5 were evaluated for their antibacterial and antifungal activities. 1, 3 and 4 were active against Enterococcus faecalis, Staphylococcus aureus, Proteus mirabilis and three Candida species, Candida albicans ATCC 9002, Candida tropicalis and Candida parapsilosis. Compound 5 was inactive against all the bacterial and fungal species used.     

Cytotoxic cassaine diterpenoid–diterpenoid amide dimers and diterpenoid amides from the leaves of Erythrophleum fordii

Detailed phytochemical investigation from the leaves of Erythrophleum fordii resulted in the isolation of 13 compounds, including three cassaine diterpenoid–diterpenoid amide dimers (1, 3 and 5), and seven cassaine diterpenoid amides (6 and 8–13), together with three previously reported ones, erythrophlesins D (2), C (4) and 3β-hydroxynorerythrosuamide (7). Compounds 1, 3 and 5 are further additions to the small group of cassaine diterpenoid dimers represented by erythrophlesins A–D. Their structures were determined by analysis of extensive one- and two-dimensional NMR experiments and ESIMS methods. Cytotoxic activities of the isolated compounds were tested against HCT-8, Bel-7402, BGC-823, A549 and A2780 human cancer cell lines in the MTT test. Results showed that compounds 1 and 3–5 exhibited significantly selective cytotoxic activities (IC₅₀ < 10 μM) against these cells, respectively.     

Five new C19-diterpenoid alkaloids from Aconitum carmichaeli

Five new aconitine-type C₁₉-diterpenoid alkaloids, namely, carmichaenine A–E (1–5), and six known diterpenoid alkaloids, namely, 14-benzoylneoline (6), neoline (7), 10-hydroxyneoline (8), neolinine (9), songoramine (10), and songorine (11), were isolated from the aerial parts of Aconitum carmichaeli. Their structures were determined by extensive spectroscopic methods, especially 2D NMR analyses. Compounds 8 and 9 were isolated for the first time from A. carmichaeli.     

Diterpenoids from the aerial parts of Orthosiphon aristatus var. aristatus

Seven new isopimarane diterpenoids, orthoarisins A?G (1–7), a new secoisopimarane diterpenoid, orthoarisin H (8), a new staminane diterpenoid, orthoarisin I (9), together with 15 previously reported diterpenoids were isolated from the aerial parts of Orthosiphon aristatus var. aristatus. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 13, 17, and 23 showed weak inhibitory activity on the proliferation of the SKOV3, DU145, and PC-3 cell lines.     

Two new lathyrane-type diterpenoid glycosides with IL-6 production inhibitory activity from the roots of Euphorbia kansui

As part of our ongoing search for anti-inflammatory compounds from higher plants, we isolated and elucidated two new diterpenoid glycosides, kansuingol A (1) and kansuingol B (2), from the roots of Euphorbia kansui. These structures were elucidated by extensive spectroscopic methods such as NMR and MS. Compounds were assessed for their IL-6 production inhibitory activity in PMA?+?A23187-stimulated HMC-1 cells. As a result, compounds 1 and 2 exerted inhibitory activities in the production of IL-6 with IC₅₀ values of 2.96, and 1.94?μM, respectively. Further, kansuingol A (1) decreased mRNA expressions of TNF-α and IL-6.     

Five new alkaloids from Aconitum apetalum (Ranunculaceae)

Twenty-one alkaloids, including five new ones, acoapetaldines A–E (1–5), were isolated from the whole plants of Aconitum apetalum. Among them, 1 is an aconitine-type diterpenoid alkaloid, 2 and 3 are aporphine alkaloids and 4 and 5 are napelline-type diterpenoid alkaloids. The structures of the new alkaloids were elucidated by spectroscopic data analysis and that of acoapetaldine D (4) was confirmed by single crystal X-ray crystallography. Acoapetaldine A (1) and aconorine (12) exhibited moderate anti-tobacco mosaic virus (anti-TMV) activity, while corydine (15) displayed moderate antimicrobial activity against Pseudomonas aeruginosa.     

TNF-α inhibitory diterpenoids from the Chinese mangrove plant Excoecaria agallocha L.

Chemical examination of the stems and twigs of the mangrove plant Excoecaria agallocha L. resulted in the isolation of six ent-kaurane diterpenoids named agallochaols K–P (1–6), an atisane-type diterpenoid agallochaol Q (7), along with eight known diterpenoids (8–15). Their structures were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR spectroscopic data with those reported in literature, in association with the biogenetic relationship with the X-ray structure of 9. Compounds 1, 5–7, 9–10, and 13 showed anti-inflammatory potency to suppress expression of NF-κB and AP-1 targeted genes including TNF-α and IL-6 induced by lipopolysaccharide (LPS) in mouse macrophages Raw 264.7 cells. In addition, compounds 1, 5–7, 9–10, and 13 block NF-κB activation, while compounds 1 and 7 block AP-1 activation dramatically, indicating these compounds possess an anti-inflammatory potential in vitro.     

Chemical constituents from the leaves of Cinnamomum parthenoxylon (Jack) Meisn. (Lauraceae)

Phytochemical investigation of the ethanolic extract from the leaves of Cinnamomum parthenoxylon (Jack) Meisn. led to the isolation of (3R, 4R, 3′R, 4′R)-6,6′-dimethoxy-3, 4, 3′, 4′-tetrahydro-2H, 2′H-[3, 3′]bichromenyl-4, 4′-diol (1), 4-hydroxybenzaldehyde (2), 1,2,4-trihydroxybenzene (3), kaempferol-3-O-α-l-rhamnoside (4), herbacetin (5), quercetin-3-O-α-l-rhamnoside (6), daucosterol (7), and β-sitosterol (8). The structures were established by extensive analysis of their MS and NMR spectroscopic data and comparison with literature data. In the present research, all of the isolated compounds 1–8 are reported for the first time in the species C. parthenoxylon. Compounds 1–6 were firstly isolated from genus Cinnamomum. Compounds 1, 3, 5 and 6 have not been reported from any species in Lauraceae family. The chemotaxonomic significance of the isolated compounds is discussed.     

The synthesis of new deoxynitroinositols by cyclization of 6-deoxy-3-O-methyl-6-nitro-d-allose and -l-talose

6-Deoxy-3-O-methyl-6-nitro-d-allose (5) and -l-talose (6) were synthesized from 1,2-O-isopropylidene-3O-methyl-α-d-allofuranose (1) by the nitromethane method via their furanoid, 1,2-O-isopropylidene derivatives (2 and 3). The barium hydroxide-catalyzed cyclization of the free nitrohexoses (5 and 6) was investigated. Under conditions favoring kinetic control (pH ～8, 0°), 5 gave mainly 1d-5-deoxy-2-O-methyl-5-nitro-allo-inositol (7), with the 1l-epi-1 (8) and epi-6 (9) stereoisomers as minor products. Compound 6 afforded a high yield of the myo-5-isomer (11); the 1l-allo-5 (13) and 1d-epi-1 (14) isomers were formed in small proportions but not isolated. The thermodynamically controlled, mutual interconversion of the stereoisomeric products was studied, as was the formation of nitronate salts and the regeneration of free nitroinositols. Upon immediate acidification, the nitronate obtained from 11 gave 11 and the neo-2 epimer (12) in a ratio of 2:3. The nitronate produced by 7 underwent rapid β-epimerization. The five isolated deoxynitroinositol monomethyl ethers were further characterized as tetra-acetates (7a, 9a, 11a, and 12a) and isopropylidene derivatives (7b, 8b, and 9b).     

Three new hetisine-type diterpenoid alkaloids from Aconitum coreanum

Three new hetisine-type diterpenoid alkaloids, Guan-fu base V (GFV, 1), Guan-fu base W (GFW, 2) and Guan-fu base X (GFX, 3) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics. Their structures were established by direct interpretation of their spectral data, mainly high resolution electrospray ionization mass spectrometry (HR-ESI-MS), ¹D and ²D NMR (¹H–¹H COSY, ROESY, HSQC and HMBC). GFX is the third N-oxygenated hetisine-type diterpenoid alkaloid isolated from A. coreanum.     

Three daphnane diterpenoids from Trigonostemon xyphophylloides

Three daphnane diterpenoid trigoxyphins U–W (1–3), together with two known daphnane diterpenoids (4 and 5) were isolated from Trigonostemon xyphophylloides. Their structures were elucidated by spectroscopic analysis. Compound 3 showed modest cytotoxicity against BEL-7402, SPCA-1 and SGC-7901 cancer cell lines.     

Specific spectral assignments for acetoxyl-group resonances in proton magnetic resonance spectra of methyl β-D-glucopyranoside tetraacetate and related derivatives

Methyl β-D-glucopyranoside tetraacetates (1) having a trideuterioacetyl group at O-2 (1a), O-3, (1b), O-4 (1c), and O-6 (1d) were synthesized by unambiguous routes to permit assignment of each individual acetoxyl-group signal in the p.m.r. spectrum of 1. The 6-acetoxyl resonance appears at lower field than signals of the other acetoxyl groups in carbon tetrachloride, chloroform-d, and methyl sulfoxide-d₆, but in pyridine-d₅ and benzene-d₆, the 2-acetoxyl-group signal appears at lower field. The acetoxyl resonances of methyl 2,3,4-tri-O-acetyl-6-O-trityl-β-D-glucopyranoside (2), methyl 2,3,4-tri-O-acetyl-β-D-glucopyranoside (3), methyl 2,3-di-O-acetyl-4,6-O-benzylidene-β-D-glucopyranoside (5), methyl 2,3-di-O-acetyl-β-D-glucopyranoside (6), methyl 2,3,6-tri-O-acetyl-β-D-glucopyranoside (7), and methyl 2,3-di-O-acetyl-6-O-trityl-β-D-glucopyranoside (12) were assigned similarly after synthesis of the 2-(trideuterioacetyl) (2a, 3a, 5a, 6a, 7a, and 12a), 3-(trideuterioacetyl) (2b, 3b, 5b, 6b, 7b, and 12b), 4-(trideuterioacetyl) (2c and 3c), and 6-(trideuterioacetyl) (7c) analogues. In chloroform-d and benzene-d₆, the 4-acetoxyl resonance appeared at about 0.3 p.p.m. to higher field than the other acetoxyl-group signals of 2. In chloroform-d and methyl sulfoxide-d₆, the 3-acetoxyl resonance is observed at highest field in compounds 1, 3, and 5. In all of these instances, the 4-hydroxyl group is substituted by an acetyl or benzylidene group. When no 4-substituent is present (compounds 6, 7, and 12), the 3-acetoxyl group resonates at lower field than the other acetoxyl groups.     

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.     

Antimicrobial terpenoids of Gossypium: Hemigossypol, 6-methoxyhemigossypol and 6-deoxyhemigossypol

The sesquiterpenoid aldehydes, hemigossypol (1a), 6-methoxyhemigossypol (1b), and 6-deoxyhemigossypol (1c), were isolated and identified from Verticillium-infected stele tissue of Gossypium barbadense. Structures were established by spectral (UV, IR, NMR, MS) evidence and chemical transformations. This is the first report of (1b) and (1c) in nature, and of NMR and m.p. data for crystalline pure (1a). Compound (1a) occurred in diseased stele tissues of all 21 Gossypium species examined and in the genera, Cienfuegosia, Gossypioides, Hampea, and Thespesia; it was absent in three Hibiscus spp. Compound (1b) occurred in the same taxa as (1a), except that it was absent in species of two cytogenetic groups (A and B genome) of Gossypium. Compound (1c) occurred in trace quantities, or was not detected, in most species; however, its distribution appeared to besimilar to that     

Chemical constituents from the aerial sections of Ajania potaninii

Nineteen compounds were isolated from Ajania potaninii, including one sulfur paraffin (1), one monoterpene (6), one lactone (3), one aliphatic acid (15), two sterols (8 and 10), one triterpenes (13), one alkaloid (18), eleven flavonoids (2, 4, 5, 7, 9, 11, 12, 14, 16 and 17) and one cyclic amide (19). All of these compounds were obtained from A. potaninii for the first time. This is the first report of N-nonanemercaptan (1), 3-hydroxy-5-decanolide (3), cirsiliol (5), 1,2,4-trihydroxy-p-mentane (6), 6-methoxytricin (7), eriodictyol (11), pectolinarigenin (12), 3,3′-di-O-methylquercetin (14), tetradecanoic acid (15), lappaconitine (18) and 1,1′,1″,1‴,1‴'-tricontane lactam (19) from the genus Ajania. The occurrence of compounds 18 and 19 in A. potaninii warrants further study.     

Chemical constituents of Euphorbia peplus

Phytochemical investigation of the whole plant of Euphorbia peplus Linn. led to the isolation of previously uncharacterized jatrophane type diterpenoid euphopepluanone L (1), along with seven known compounds, including three diterpenes (2–4), three bisnorsesquiterpenes (5–7), and a monoterpene (8). Their chemical structures were established based on extensive spectroscopic analysis. Compounds 3 (20-deoxyingenol) and 5–8 were firstly isolated from E. peplus, while PBI 345 (5) reported from the genus for the first time. Furthermore, the chemotaxonomic significance of the isolates was discussed.     

Fatty acid derivatives and dammarane triterpenes from the glandular trichome exudates of Ibicella lutea and Proboscidea louisiana

Ibicella lutea and Proboscidea louisiana, both of the Martyniaceae family, are known for rich glandular trichomes on their leaves and stems. Chemical investigations of the glandular trichome exudates on leaves of the two plants furnished three types of secondary metabolites, glycosylated fatty acids, glycerides (2-O-(3,6-diacetyloxyfattyacyl)glycerols and 2-O-(3-acetyloxyfattyacyl)glycerols) and dammarane triterpenes. The glycosylated fatty acids from I. lutea were determined to be 6(S)-(6-O-acetyl-β-d-glucopyranosyloxy)-octadecanoic acid (1A), -eicosanoic acid (1B) and -docosanoic acid (1C), as well as their respective deacetyl congeners (2A, 2B and 2C), whereas P. louisiana furnished 8(S)-(6-O-acetyl-β-d-glucopyranosyloxy)-eicosanoic acid (3A) and -docosanoic acid (3B) and their respective deacetyl congeners (4A and 4B), together with 2B. Both plants contained 12 identical 2-O-[(3R,6S)-3,6-diacetyloxyfattyacyl]glycerols (5A-L), in which the fatty acyl moieties contained between 17 and 21 carbon atoms. The corresponding mono-acetyloxy compounds, 2-O-[(3R)-3-acetyloxyfattyacyl]glycerols (6A–L) were detected in both plants. Among these glycerides, ten compounds (5A, 5C, 5F, 5H, 5K, 6A, 6C, 6F, 6H and 6K) had iso-fattyacyl structures and four (5E, 5J, 6E and 6J) had anteiso-fattyacyl structures. A previously unknown dammarane triterpene, betulatriterpene C 3-acetate (7), was isolated together with three known dammarane triterpenes, 24-epi-polacandrin 1,3-diacetate (8), betulatriterpene C (9) and 24-epi-polacandrin 3-acetate (10) from I. lutea, whereas 12 dammarane triterpenes, named probosciderols A–L (12–23), and the known compound betulafolienetriol (11) were isolated from P. louisiana. The structures of these compounds were elucidated by spectroscopic analysis including 2D-NMR techniques and chemical transformations. The 6-O-acetylglucosyloxy-fatty acids 1A–C (42%) and the dammarane triterpenes 7–10 (31%) were the two most abundant constituents in the glandular trichome exudate of I. lutea, whereas the dammarane triterpenes 11–23 (47%) and the glucosyloxy-fatty acids (4A, 4B and 2B) (38%) were the most abundant constituents in the glandular trichome exudate of P. louisiana.     

Chemical constituents from the roots of Cichorium glandulosum Boiss. et Huet (Asteraceae)

A phytochemical investigation of the roots extract of Cichorium glandulosum led to the isolation and characterization of fourteen compounds, including five sesquiterpene lactones (1–5), five flavonoids (6–10), and four lignans (11–14). Their structures were determined by spectroscopic data analysis and comparison with the literatures. This is the first report of the crystal data of lactucopicrin (1). This is the first time to report the isolation of 6,8,11-epi-desacetylmatricarin (2), desacetylmatricarin (3), ixerisoslde C (4), magnodelavin (5), 2ʹ,4-dihydroxy-4ʹ-methoxy-6ʹ-O-β-glucopyranoside dihydrochalcone (6), (−)-evofolin B (7), isoquercitrin (8), myricetin 7-methyl-ether-3-O-glucoside (9), (+)-medioresinol (12), 4-O-methylcedrusin [2-(3ʹ,4ʹ-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzofuran-5-propan-1-ol] (13), and (2R,3S)-samwirin A (14) from C. glandulosum. Among them, compounds 5, 9, 13, and 14 were obtained from Asteraceae family for the first time. The chemotaxonomic significance of all the isolates 1–14 was discussed.     

Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines of cassaine diterpenoids from the bark of Erythrophleum fordii

A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (3) from a natural source and that of the remaining eight known diterpenoids (4–5, 8–13) from E. fordii. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (1–13) was examined in vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (6–10, 12, 13) exhibited potent cytotoxic activity against all three cell lines with IC₅₀ values between 0.4 μM and 5.9 μM. Erythroformine B (7) significantly induced apoptosis in all three cancer cells in a concentration-dependent manner.     

Two dimeric lignans with an unusual α,β-unsaturated ketone motif from Zanthoxylum podocarpum and their inhibitory effects on nitric oxide production

Two new dimeric lignans, zanthpodocarpins A (1) and B (2), and five known lignans, eudesmin (3), (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (4), dimethoxysamin (5), rel-(1R,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octan-2-one (6), and magnone A (7), were isolated from the barks of Zanthoxylum podocarpum. Their structures were identified by using spectroscopic methods. Compounds 1 and 2 are rare dilignans bearing an unusual α,β-unsaturated ketone group from a natural source. Bioassay showed that compounds 1 and 2 could inhibit nitric oxide (NO) production in LPS stimulated RAW 264.7 cells with IC₅₀ values of 5.31 μM and 12.15 μM, respectively.