New flavanones from the leaves of Cryptocarya chinensis and their antituberculosis activity

Four new flavanones, cryptoflavanones A-D (1-4, resp.), together with eight known compounds, were isolated from the leaves of Cryptocarya chinensis. The structures of these new compounds were determined by spectral analyses. Among the isolated compounds, pinocembrin (5) and cryptocaryone (6) exhibited antituberculosis activity against Mycobacterium tuberculosis H(37) Rv strain in vitro with MIC values of 3.5 and 25.0 μg/ml, respectively.     

Acylated protopanaxadiol-type ginsenosides from the root of Panax ginseng

Six new protopanaxadiol-type ginsenosides, named ginsenosides Ra(4) -Ra(9) (1-6, resp.), along with 14 known dammarane-type triterpene saponins, were isolated from the root of Panax ginseng, one of the most important Chinese medicinal herbs. The structures of the new compounds were determined by spectroscopic methods, including 1D- and 2D-NMR, HR-MS, and chemical transformation as (20S)- 3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[β-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (1), (20S)-3-O-[β-D-6-O-acetylglucopyranosyl-(1→2)-β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (2), (20S)-3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (3), (20S)-3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[α-L-arabinopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (4), (20S)-3-O-{β-D-4-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[α-L-arabinofuranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (5), (20S)-3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[α-L-arabinofuranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (6). The sugar moiety at C(3) of the aglycone of each new ginsenoside is butenoylated or acetylated.     

Novel alkaloids from the roots of Stemona sessilifolia

Four new Stemona alkaloids, sessilistemonamines A-C (1-3, resp.) and dihydrostemoninine (4), were isolated from the roots of Stemona sessilifolia. Their structures and relative configurations were elucidated by means of in-depth 1D- and 2D-NMR-spectroscopic as well as mass-spectrometric experiments; and the structure of 4 was solved by X-ray single-crystal diffraction. The stereoisomeric compounds 1-3 share an unprecedented tetracyclic decahydro-1H-furo[2',3':4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus. Compounds 1 and 2 were found to be moderately active in terms of acetylcholinesterase (AchE) inhibition, with IC50 values of 68.8+/-9.5 and 17.1+/-2.5 microM, resp.     

Three new constituents from the roots of Erythrina variegata and their antibacterial activity against methicillin-resistant Staphylococcus aureus

Two new isoflavonoids, eryvarins V and W (1 and 2, resp.), and a new chromen-4-one derivative, eryvarin X (3), along with three known isoflavonoids, 4-6, were isolated from the roots of Erythrina variegata. Their structures were established by spectroscopic analyses. Compound 1 is a rare naturally occurring isoflavanone which possesses a OH group at C(3). Among the new compounds 1-3, 2 exhibited a potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains.     

Three new cytotoxic Diels-Alder-type adducts from Morus australis

Three new natural products, australisines A-C (1-3, resp.), were isolated from the stem bark of Morus australis, together with eight related compounds, including mulberrofurans E-G, J, and Q, mongolicin C, chalcomoracin, and kuwanon G. Their structures were fully characterized by spectroscopic methods. Compounds 1-3, mulberrofuran G, mongolicin C, and chalcomoracin showed moderate cytotoxic activities against five human cancer cell lines, with IC50 values ranging from 4.6-9.2 microg/ml, as determined by MTT assay.     

D-ring-opened phragmalin-type limonoids from Chukrasia tabularis var. velutina

Five new D-ring-opened phragmalin-type limonoids, tabulalins A-E (1-5, resp.), were isolated from the stem bark of Chukrasia tabularis var. velutina. In the structures of these new isolates, the D-ring (C(16)/C(17) δ-lactone ring) of phragmalins was cleaved, and rare C(16)/C(30) δ-lactone ring in 1-3 or C(16)/C(8) γ-lactone ring in 4 and 5 were formed. The structures of these new compounds were elucidated based on extensive 1D- and 2D-spectroscopic analyses (HSQC, HMBC, and ROESY) and HR-ESI-MS. The major compounds, 2, 3, and 5, were evaluated for their inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a macrophage (RAW264.7) cell line with IC(50) values of 15.3±0.6, 13.0±0.5, and 17.1±0.7 μM, respectively.     

Cytotoxic withanolides from Physalis angulata L

Four new withanolides, physagulins L-O (1-4), were isolated from the MeOH extract of the aerial parts of Physalis angulata L. (Solanaceae), together with seven known withanolides, compounds 5-11. Their structures were determined by spectroscopic techniques, including 1H-, 13C-NMR (DEPT), and 2D-NMR (HMBC, HMQC, 1H,1H-COSY, NOESY) experiments, as well as by HR-MS. All eleven compounds were tested for their antiproliferative activities towards human colorectal-carcinoma (HCT-116) and human non-small-cell lung-cancer (NCI-H460) cells. Compound 5 exhibited the highest anticancer activity against the HCT-116 cell line, with an IC50 value of 1.64+/-0.06 microM. Compound 9 exhibited the highest cytotoxicity towards the NCI-H460 cell line, with an IC50 value of 0.43+/-0.02 microM.     

Secophnane-type alkaloids from Daphniphyllum oldhami

Four new alkaloids, daphnioldhanins D-G (1-4, resp.), together with five known alkaloids, daphmacropodine (5), secodaphniphylline (6), deoxycalyciphylline B (7), deoxyisocalyciphylline B (8), and daphmanidin A (9), were isolated from the roots of Daphniphyllum oldhami. Their structures were elucidated on the basis of spectroscopic data and chemical methods. Compound 1 at 2.0 microM showed potent antioxidant activity against H(2)O(2)-induced impairment in PC12 cells.     

New hepatoprotective coumarinolignoids from Mallotus apelta

Three new coumarinolignoids, malloapelins A-C (1-3, resp.), together with three known coumarinolignoids, cleomiscosin A (4), cleomiscosin B (5), and 5'-demethylaquillochin (6), were isolated from the roots of Mallotus apelta MUELL.-ARG. Compounds 1-6 are three pairs of regioisomeric coumarinolignoids. Their structures were elucidated on the basis of spectral evidence. Compounds 3 showed promising hepatoprotective activity against D-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial stem-like cells.     

Ficuschlorins A - D, lactone Chlorins from the leaves of ficus microcarpa

Four new lactone chlorins, ficuschlorins A – D ( 1 – 4 , resp.), and six known pheophytins were isolated from the leaves of Ficus microcarpa. The structures of these compounds were determined by 1D‐ and 2D‐NMR spectroscopy, and other techniques. New natural pheophytins were rarely obtained. In the past ten years, only three new pheophytins were isolated from natural sources.     

Three new cytochalasins from the marine-derived fungus Spicaria elegans KLA03 by supplementing the cultures with L- and D-tryptophan

Three new cytochalasins Z₂₁–Z₂₃ ( 1 – 3 , resp.), together with five analogs, 4 – 8 , were isolated from Spicaria elegans KLA03 by the OSMAC (one strain‐many compounds) approach with adding L ‐ and D ‐tryptophan during its cultivation. The structures of new cytochalasins were elucidated on the basis of comprehensive 1D‐ and 2D‐NMR and HR‐ESI‐MS analyses. Cytochalasins Z₂₁ and Z₂₂ ( 1 and 2 , resp.), and compound 5 showed cytotoxic activities against A‐549 cell lines with IC₅₀ values of 8.2, 20.0, and 3.1 μM , respectively.     

Bioactive marine prostanoids from octocoral Clavularia viridis

Chemical investigation of the nonpolar extract of soft coral Clavularia viridis resulted in isolation of five new prostanoids, designated as claviridic acids A-E (1-5, resp.), in addition to the known clavulones I-III. Their structures were determined on the basis of spectroscopic techniques, especially HR-ESI-MS, CD, and 2D-NMR experiments. The isolated marine prostanoids exhibited potent inhibitory effect on PHA-induced proliferation of peripheral blood mononuclear cells (PBMC), as well as significant cytotoxic activity against human gastric cancer cells (AGS).     

New bioactive clerodane diterpenoids from the roots of Casearia membranacea

Bioassay-guided fractionation of the acetone extract of the roots of Casearia membranacea furnished three new clerodane diterpenes, caseamembrins S-U (1-3) and the known caseamembrin Q (4). Their structures were established by extensive spectroscopic analyses, especially 2D-NMR. Compounds 1-4 were tested against human tumor cells, including HeLa (cervical epitheloid carcinoma), DLD-1 (colon carcinoma), Daoy (medulloblastoma), and KB (oral epidermoid carcinoma) cell lines. Caseamembrin T (2) exhibited the most potent activity against Daoy cells (ED(50)=10 ng/ml), superior to that of the standard drug mitomycin.     

New cytotoxic prostanoids from Taiwanese soft coral Clavularia viridis

Chemical investigation of the AcOEt/MeOH extract of Clavularia viridis collected in Taiwan has afforded four new prostanoids, named claviridins A-D (1-4, resp.). The structures of compounds 1-4 were determined on the basis of 1D- and 2D-NMR techniques, including COSY, HMQC, HMBC, and NOESY experiments. Pharmacological studies revealed that compounds 1-4 exhibited potent cytotoxicity against human cancer cells.     

Phenolic compounds from the whole plants of Gentiana rhodantha (Gentianaceae)

Gentiana rhodantha Franch. ex Hemsl. (Gentianaceae), an annual herb widely distributed in the southwest of China, has been medicinally used for the treatment of inflammation, cholecystitis, and tuberculosis by the local people of its growing areas. Chemical investigation on the whole plants led to the identification of eight new phenolic compounds, rhodanthenones A–D ( 1 – 4 , resp.), apigenin 7‐O‐glucopyranosyl‐(1→3)‐glucopyranosyl‐(1→3)‐glucopyranoside ( 5 ), 1,2‐dihydroxy‐4‐methoxybenzene 1‐O‐α‐L ‐rhamnopyranosyl‐(1→6)‐β‐D ‐glucopyranoside ( 6 ), 1,2‐dihydroxy‐4,6‐dimethoxybenzene 1‐O‐α‐L ‐rhamnopyranosyl‐(1→6)‐β‐D ‐glucopyranoside ( 7 ), and methyl 2‐O‐β‐D ‐glucopyranosyl‐2,4,6‐trihydroxybenzoate ( 8 ), together with eleven known compounds, 9 – 19 . Their structures were determined on the basis of detailed spectroscopic analyses and chemical methods. Acetylcholinesterase (AChE) inhibition and cytotoxicity tests against five human cancer cell lines showed that only rhodanthenone D ( 4 ) and mangiferin ( 12 ) exhibited 18.4 and 13.4% of AChE inhibitory effects at a concentration of 10⁻⁴ M , respectively, while compounds 1 – 5 and the known xanthones lancerin ( 11 ), mangiferin ( 12 ), and neomangiferin ( 13 ) displayed no cytotoxicity at a concentration of 40 μM .     

Woody pretzels: spirocycles from vetiver to patchouli and Georgywood

This review, including new experimental results, is the summary of a talk at the RSC/SCI conference 'flavours & fragrances 2007' in London, Imperial College, 24-26 September, 2007. Though the third dimension of the receptor models of J. E. Amoore rarely was exceeding 4 A, the world of woody odorants such as (+)-cedrol (3; cedarwood), (-)-khusimone (4; vetiver), and (-)-patchoulol (5; patchouli) is anything but flat. Any tricyclic skeleton with a zero-bridge contains a spirocyclic ring system determining its 3D structure, so spirocycles (spira, Lat. pretzel) are the fastest access to the third dimension. In the vetiver family, a spirocyclic mimic 9 of (-)-khusimone (4) was first discovered by chance by Büchi in 1976, and also by chance, we obtained another system, 12, with a characteristic vetiver smell by tandem-Rupe-Nazarov reaction of alkyne diols. A 5-A distance between a quaternary C-atom and a carbonyl group (or alternative HB acceptor) with an alpha-methyl or methylene branching is proposed to be the key to their vetiver odor. Upon scale-up of one of these odorants, 24, we discovered a very powerful (0.067 ng/l) impurity with a most typical patchouli scent: the spirocyclic, sterically crowded hydroxy ketone 33--a most unusual structure for a patchouli odorant. Several spirocyclic hydroxy ketone analogs, also with inverted ring systems such as in 70 and 84, provided new insights into the structure-odor correlation of this family. A superposition analysis indicated the carbonyl function of the hydroxy ketone to overlay on the geminal dimethyl motive of (-)-patchoulol. And indeed, the corresponding hydroxy ketone of patchoulol, 59, synthesized in 13 steps from Cyclal C (63), also emanated a patchouli odor. Finally, the synthesis and olfactory properties of twelve rigid spirocyclic analogs, 95-97, 99-102, and 106-110, of Georgywood (91) are presented that highlight stereochemical requirements for woody odorants and raise doubts about an alpha-helical binding motive postulated by Hong and Corey.     

Influence of (hydroxymethyl)pyridine and pyridine-carboxylic acids, in trans-position to the isopropylamine and amine ligands, on the cytotoxicity of platinum complexes

trans-Pt(II) Complexes with aliphatic amines and planar amines such as (hydroxymethyl)pyridines, and pyridine-3- and pyridine-4-carboxylic acids were synthesized and screened for their potential cytotoxic activity in different cancer cell lines used at the NCI for in vitro screens, i.e., MCF7, NCIH460, and SF268. The complexes studied were designed to differ in geometrical parameters such as the position of the phenyl-group substituents and the nature of the substituents themselves for gathering information about the structure-activity relationships in the trans-complexes. The variation of the substituents turns to be crucial for their biological activity, as both pyridine-3- and pyridine-4-carboxylic acids in trans-position to both amine and isopropylamine ligands provided complexes which displayed no specificity toward any type of cell tested, while (hydroxymethyl)pyridine in trans-position to isopropylamine ligands led to complexes that were clearly more effective against the cell lines tested.     

Lobophytones U - Z₁, biscembranoids from the Chinese soft coral Lobophytum pauciflorum

Chemical examination of a Chinese soft coral Lobophytum pauciflorum resulted in the isolation of seven new biscembranoids named lobophytones U–Z₁ ( 1 – 7 , resp.), together with methyl sartortuoate ( 8 ) and nyalolide ( 9 ). The structures of the new compounds were elucidated by 1D‐ and 2D‐NMR (COSY, HSQC, HMBC, and NOESY) spectroscopic analysis in association with MS and IR data. All compounds were tested against lipopolysaccharide (LPS)‐induced nitric oxide (NO) release in mouse peritoneal macrophage. Lobophytone Z ( 6 ) inhibited NO production with an IC₅₀ value of 2.6 μM . Lobophytone H ( 1 ) showed inhibitory activities against the bacteria S. aureus and S. pneumoniae.     

6,7-seco-ent-kaurane diterpenoids from Isodon sculponeatus with cytotoxic activity

Six new 6,7‐seco‐ent‐kaurane diterpenoids, sculponeatins N–S ( 1 – 6 , resp.), together with eleven known analogues, 7 – 17 , were isolated from the aerial parts of Isodon sculponeatus. The structures of compounds 1 – 6 were elucidated by spectroscopic methods including extensive 1D‐ and 2D‐NMR experiments, as well as HR‐ESI‐MS analysis. All diterpenoids obtained were assayed for their cytotoxic activity against K562 and HepG2 human tumor cell lines. Among them, compound 1 showed the most significant cytotoxicity with the IC₅₀ values of 0.21 and 0.29 μM , respectively. The structure–activity relationships are discussed.     

Identification and Antifeedant Activities of Limonoids from Azadirachta indica

Four new limonoids, azadiraindins A–D ( 1 – 4 , resp.), together with seven known analogs, were isolated from the MeOH extract of Azadirachta indica. The structures of 1 – 4 were elucidated by NMR and MS spectroscopic analyses, and the relative configuration of 1 was determined by single‐crystal X‐ray crystallography. The compounds isolated in comparatively large amount were evaluated for their antifeedant activities against Plutella xylostella; the antifeedant rate of 10 was 90.6% and the corrected mortality of 8 was 79.2%.