Eudistomidin G,a new β-carboline alkaloid from the Okinawan marine tunicate Eudistoma glaucus and structure revision of eudistomidin B

A new β-carboline alkaloid, eudistomidin G (1), has been isolated from the Okinawan marine tunicate Eudistoma glaucus, and the structure was elucidated from spectroscopic data. Furthermore, the structure of eudistomidin B (2), which has been isolated from the same tunicate, was revised from 2a to 2b by detailed analyses of spectroscopic data. Asymmetric synthesis of the revised structure (2b) of eudistomidin B (2) and its (1S,10S)-diastereomer (2c) has been accomplished with the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configuration of eudistomidin B (2) was confirmed to be 2b possessing (1R,10S)-configuration, from comparison of the ¹H NMR data, CD spectra, [α]_D values, and HPLC analysis of 2b, 2c, and natural eudistomidin B.     

Depsidones and other constituents from Phomopsis sp. CAFT69 and its host plant Endodesmia calophylloides with potent inhibitory effect on motility of zoospores of grapevine pathogen Plasmopara viticola

In our search for secondary metabolites regulating the motility behavior of zoospores of the grapevine downy mildew pathogen Plasmopara viticola, we found that extracts from an endophytic fungus Phomopsis sp. CAFT69 and its host plant Endodesmia calophylloides remarkably impaired motility of zoospores followed by lysis. The active principles in the extracts were isolated and identified as two new compounds, namely excelsional (1a) and 9-hydroxyphomopsidin (2a), together with excelsione (1b), phomopsidin (2b), alternariol (3a), alternariol-5-O-methyl ether (3b), the hitherto undescribed 5′-hydroxyalternariol (3c), altenusin (4) from the fungus, xanthochymol (5) and 1,5-dihydroxy-3-methoxyxanthone (mesuaxanthone, 6) from the plant. Bioassays revealed that compounds 1a/b, 2a/b, and 3a–6 displayed motility inhibition and lytic activities against zoospores of the grapevine downy mildew pathogen P. viticola in a dose- and time-dependent manner from 1 to 10 μg/mL. Their structures were elucidated by extensive spectroscopic analyses including 2D NMR techniques. This is the first report of an endophyte and its natural products from E. calophylloides and the first isolation of compounds 5 and 6 from this plant.     

Five-coordinate zinc(II) complexes with optically active Schiff bases derived from (1R,2R)-(−)cyclohexanediamine: X-ray structure and CP MAS NMR characterization of [cyclohexylenebis(5-chlorosalicylideneiminato)zinc(II)pyridine] and [cyclohexylenebis(5-bromosalicylideneiminato)zinc(II)pyridine]

Schiff bases obtained from (1R,2R)-(−)-cyclohexanediamine and 5-chloro- (1) or 5-bromosalicylaldehyde (2) are used as ligands for Zn(II) resulting in [(1R,2R)-cyclohexylenebis(5-chlorosalicylideneiminato)]zinc(II) (1a) and (1R,2R)-[cyclohexylenebis-(5-bromosalicylideneiminato)]zinc(II) (2a). In the presence of pyridine, 1a and 2a turned out into (1R,2R)-[cyclohexylenebis(5-chlorosalicylideneiminato)pyridine]zinc(II) (1b) and (1R,2R)-[cyclohexylenebis(5-bromosalicylideneiminato)pyridine]zinc(II) (2b). Coordination sphere of Zn(II) atoms in both pyridine adducts is a slightly distorted square pyramid, with N₂O₂ chromophore units and axially bonded pyridine as it is evident from single crystal X-ray analyzes of 1b and 2b. The asymmetric unit of 1b and 2b contains two molecules of complexes. The observed distances of Zn-O in both molecules indicate the rigidity of the tetradentate ligand as a main factor influencing the geometry of coordination sphere. Obtained complexes were characterized by ¹H NMR in solution and ¹³C CP MAS NMR. NOE differential experiments revealed significant steric interactions between C(6)-H in the phenyl ring, cyclohexyl C(1)-H and imine hydrogen. Significant coordination shifts of carbons in the closest proximity to the coordination center were noted as well.     

Neolignans from Aniba lancifolia

The branches of the shrub Aniba lancifolia Kubitzki et Rodrigues (Lauraceae) contain besides 2-hydroxy-4,5- dimethoxyallylbenzene and its dimer cyclohexan-2-allyl- 5-en-4,5-dimethoxy-4-O-(2′-allyl-4′,5′-dimethoxyphenyl)-1-one (lancilin, 2) 6 further novel neolignans: (4S,2′R)- and (4R,2′E)-cyclohexan-2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-guaiacyl)-propyl]-1-one (lancifolins A and B, 3a and 3b), (4S,2′R)- and (4R,2′R)-cyclohexan- 2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-veratryl)-propyl]-1-one (lancifolins C and D, 3c and 3d), (4S,2′R)-and (4R,2′R)-cyclohexan-2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-piperonyl)-propyl]-1-one (lancifolins E and F, 3e and 3f).     

Phytochemical and chemotaxonomic study on Piper pleiocarpum Chang ex Tseng

The phytochemical study of Piper pleiocarpum Chang ex Tseng led to the isolation of eighteen compounds (1–18), including ten lignanoids, galbelgin (1), (+) sesamin (2), denudatin A (3), hancinone (4), (7S,8S, 3′R)-Δ^8'-3,3′,4-trimethoxy-3′,6′-dihydro-6′-oxo-7.0.4′,8.3′-lignan[(2S,3S,3aR)-2-(3,4-dimethoxyphenyl)-3,3a-dihydro-3a-methoxy-3-methyl-5-(2-propenyl)-6(2H))-benzofuranone] (5), (−)-(7R,8R)-machilin D (6), (1R,2R)-2-[2-methoxy-4-((E)-prop-1-enyl)phenoxy]-1-(3,4-dimethoxyphenyl)propyl acetate (7), piperbonin A (8), machilin D (9), 4-methoxymachilin D (10), one amide alkaloid, Δ^α,β-dihydropiperine (11), six polyoxygenated cyclohexenes, ent-curcuminol F (12), uvaribonol E (13), ellipeiopsol A (14), 1S,2R,3R,4S-1-ethoxy-2-[(benzoyloxy)methyl]cyclohex-5-ene-2,3,4-triol, 3-acetate (15), (+)-crotepoxide (16), (+)-senediol (17), and one benzoate derivative, 2-acetoxybenzyl benzoate (18). Their structures were established by spectroscopic data and by comparison with the literature. All the compounds were firstly isolated from P. pleiocarpum, while ten compounds 6–7, 9–10, 12–15, 17–18 were isolated from the genus Piper and the family Piperaceae for the first time. The chemotaxonomic significance of these compounds was also discussed. The isolation of compounds 6–7, 9–10 may be used as chemotaxonomic markers for the genus of Piper.     

Anti-hepatitis B virus lignans from the root of Streblus asper

Four new lignans, strebluslignanol F (1), (7′R,8′S,7″R,8″S)-erythro-strebluslignanol G (2), isomagnaldehyde (3) and isostrebluslignanaldehyde (4), along with 12 known lignans (5–16) were isolated from the ethyl acetate-soluble part of MeOH extract of the root of Streblus asper. Their structures were elucidated through various spectroscopic methods, including 1D NMR (¹H NMR, ¹³C NMR), 2D NMR (HMQC, HMBC and NOESY) and HRMS. The stereochemistry at the chiral centers was determined using CD spectra, as well as analyses of coupling constants and optical rotation data. The isolated lignans were evaluated for their anti-HBV activities in vitro using the HBV transfected HepG2.2.15 cell line. The most active lignans, (7′R,8′S,7″R,8″S)-erythro-strebluslignanol G, magnolol, isomagnolol and isolariciresinol, exhibited significant anti-HBV activities with IC₅₀ values of 1.58, 2.03, 10.34 and 3.67 μM, respectively, for HBsAg with no cytotoxicity, and of 3.24, 3.76, 8.83 and 14.67 μM, respectively, for HBeAg with no cytotoxicity. (7′R,8′S,7″R,8″S)-erythro-Strebluslignanol G and magnolol showed significant anti-HBV activities to inhibit the replication of HBV DNA with the IC₅₀ values of 9.02 and 8.67 μM, respectively.     

New prenylated isoflavones and a prenylated dihydroflavonol from Millettia pachycarpa

Extraction of Millettia pachycarpa Benth. gave 5,7,4′-trihydroxy-6,8-diprenylisoflavone (1a), 5,7,4′-trihydroxy-6,3′-diprenylisoflavone (2a), 5,7,3′,4′-tetrahydroxy-6,8-diprenylisoflavone (3a) and (2R, 3R)-5,4′-dihydroxy-8-prenyl-6″,6″-dimethylpyrano[2″,3″: 7,6]-dihydroflavonol (4a) whose structures were established by chemical transformations and spectroscopic means. Pectolinarigenin and salvigenin were isolated from Buddleia macrostachya Benth.     

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.     

A new carotenoid, 5,6-dihydrocrustaxanthin,from prawns and the distribution of yellow xanthophylls in shrimps

A new yellow carotenoid, named 5,6-dihydrocrustaxanthin (6), was isolated together with five yellow xanthophylls: isoastaxanthin (1), 5,6-dihydropenaeusxanthin (2), penaeusxanthin (3), tetrahydroxypirardixanthin (4), and crustaxanthin (5) from three species of prawns: Marsupenaeus japonicus, Litopenaeus vannamei, and Metapenaeus joyneri, belonging to Penaeidae. The structure of (6) was determined to be (3R,4S,5R,6R,3′R,4′S)-5,6-dihydro-β,β-carotene-3,4,3′,4′-tetrol by UV-VIS, MS, ¹H NMR, and CD spectral data. Distributions of yellow xanthophylls (1–6) in ten species of shrimps were investigated from a chemo-systematic point of view. Yellow xanthophylls (1–6) were present in only three species of prawns described above, among the ten species of shrimps investigated. Instead of 1–6, luteins and tunxanthins, having the 3-hydroxy-ε-end group, were present in other species of shrimps belonging to Penaeidae, Pandalidae, and Palaemonidae.     

Enantiomeric lignans with anti-β-amyloid aggregation activity from the twigs and leaves of Pithecellobium clypearia Benth

To develop potential agents for slowing the progression of Alzheimer′s disease, two pairs of new enantiomeric lignans, including a couple of rarely 8′,9′-dinor-3′,7-epoxy-8,4′-oxyneolignanes named (7S, 8S)- and (7R, 8R)-pithecellobiumin A (1a/1b) and a pair of 2′,9′-epoxy-arylnaphthalenes named (7R, 8R, 8′R)- and (7S, 8S, 8′S)-pithecellobiumin B (2a/2b) were separated by chiral high performance liquid chromatography (HPLC). Their planar structures were elucidated by spectroscopic data analyses. The absolute configurations were determined by comparing of experimental and calculated electronic circular dichroism (ECD). The inhibitory activity on Aβ aggregation of all optical pure compounds was tested by ThT assay. Interestingly, enantiomeric inhibitors 1a (62.1%) and 1b (81.6%) exhibited different degrees of anti-Aβ aggregation activity. However, 2a (65.4%) and 2b (68.4%) showed similar inhibition rate. The different inhibition profiles were explained by molecular dynamics and docking simulation studies.     

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.     

A pair of new tetrahydro-naphthalenone enantiomers from Eremurus altaicus (Pall.) Stev.

A new racemic mixture of a 4-hydroxytetralone derivative, altaicusin A (1), was isolated from the whole plant of Eremurus altaicus (Pall.) Stev., together with three anthraquinones (compounds 2–4) and two naphthalene derivatives (5–6). The racemic altaicusin A (1) was further purified by chiral HPLC to yield a pair of enantiomers, (+)-(4S)-altaicusin A (1a) and (−)-(4R)-altaicusin A (1b). Their structures were established on the basis of spectroscopic analysis, including IR, HR-TOF-MS, and NMR. The absolute configurations of compounds 1a and 1b were elucidated by quantum chemical ECD calculations. Compounds 3 and 6 exhibited inhibitory activity against protein tyrosine phosphatase 1B (PTP1B).     

Dihydronaphthalenones from the endophytic fungus Botryosphaeria sp. BCC 8200

Five new dihydronaphthalenones (1, 2a/2b, 3a/3b), four of which were isolated as two inseparable mixtures of isomers, together with two known compounds, 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (4) and siderin (5), were identified as secondary metabolites of the endophytic fungus Botryosphaeria sp. BCC 8200. The structures were elucidated by interpretation of NMR spectroscopic and mass spectrometry data. Compounds 2a/2b, 3a/3b, and 5 exhibited weak cytotoxic activities against cancer cell lines.     

Synthesis and biological activity of brassinolide analogues, 26,27-bisnorbrassinolide and its 6-oxo analogue

Two hitherto unknown brassinolide analogues, (22R,23R)-2α,3α,22,23-tetrahydroxy-B-homo-7-oxa-24-nor-5α-cholestan-6-one (9b) and (22R,23R)-2α,3α,22,23-tetrahydroxy-24-nor-5α-cholestan-6-one (8a), were stereoselectively synthesized. In both the Raphanus and rice-lamina inclination tests, 9b exhibited almost the same activity as brassinolide (1) and 8a also showed ca 10–50% of the activity of 1.     

Two new dihydrobenzofuran-type neolignans from Breynia fruticosa

(7S,8R,7′S)-9,7′,9′-Trihydroxy-3,4-methylenedioxy-3′-methoxy [7-O-4′,8-5′] neolignan (1) and (7S,8R,7′S)-9,9′-dihydroxy-3,4-methylenedioxy-3′,7′-dimethoxy [7-O-4′,8-5′] neolignan (2), two new natural dihydrobenzofuran-type neolignans, along with 9,9′-dihydroxy-3,4-methylenedioxy-3′-methoxy [7-O-4′,8-5′] neolignan (3) and (-)-machicendiol (4), were isolated from the whole plants of Breynia fruticosa. The structures of 1 and 2, including the absolute configurations, were determined by spectroscopic methods and circular dichroism (CD) techniques. The absolute configuration of 4 was confirmed by calculations of the OR spectrum, together with OR and ECD spectra of its p-bromobenzoate ester (4a).     

Five new iridoïd dimers from the fruits of Canthium subcordatum DC (syn. Psydrax subcordata DC)

Five new iridoid dimers, canthiumosides 1–5 (1–4 and 5a), together with nine known compounds, shanzhigenin methyl ester (6), 1-epishanzhigenin methyl ester (6′), linearin (7), 1-epilinearin (7′), mussaenoside (8), shanzhiside methyl ester (9), 3′,4′,7-trihydroxyflavone (10), betulinic acid (11), and oleanolic acid (12) were isolated from the fruits of Canthium subcordatum DC (Syn. Psydrax subcordata (DC) Bridson). The structures of these compounds were established by interpretation of their spectral data, mainly HR-TOFESIMS, 1D NMR (¹H, ¹³C and DEPT) and 2D NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY), and by comparison with the literature.     

Synthesis and in vitro antitumor activity of novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands

Four novel iridium(III) complexes with enantiopure C₂-symmetrical vicinal diamine ligands were designed, synthesized, and characterized by FT-IR, NMR, and MS. The cytotoxicities of all of the complexes against the human solid tumor cell lines A2780, A549, KB, and MDA-MB-231 were evaluated. Both R,R-configured complexes (R,R)-5a and (R,R)-5b exhibited more potent or similar activity compared with oxaliplatin, whereas their corresponding (S,S)-isomers (S,S)-5a and (S,S)-5b were found to be mostly inactive. As indicated by the activation of caspase-3, the cleavage of PARP, and the upregulation of p53, the preliminary mechanism studies revealed that the mode of cell death initiated by (R,R)-5a in A2780 cells was predominantly p53-mediated apoptosis. In addition, the structure of (R,R)-5a was unambiguously confirmed through single crystal X-ray structure determination.     

Synthesis,characterization, and in vitro antimicrobial activities of 5-alkenyl/hydroxyalkenyl-2-phenylamine-1,3,4-oxadiazoles and thiadiazoles

The long-chain alkenoic acid hydrazides (1a–d) on reaction with phenylisocyanate and phenylthiocyanate gave their corresponding semicarbazides (2a–d) and thiosemicarbazides (4a–d), which on further refluxing with POCl₃ and Ac₂O yielded corresponding 1,3,4-oxadiazoles (3a–d) and thiadiazoles (5a–d), respectively.The structure elucidation of synthesized compounds is based on the elemental analysis and spectral data (IR, ¹H NMR, ¹³C NMR and MS). The synthesized oxadiazoles and thiadiazoles have been screened for antibacterial and antifungal activities. The investigation of antimicrobial screening revealed that compounds 3c, 3d, 5c, 5d and compounds 3b, 5b, showed good antibacterial and antifungal activities, respectively.     

Minor phenolics from Angelica keiskei and their proliferative effects on Hep3B cells

A new coumarin, (?)-cis-(3′R,4′R)-4′-O-angeloylkhellactone-3′-O-β-d-glucopyranoside (1) and two new chalcones, 3′-[(2E)-5-carboxy-3-methyl-2-pentenyl]-4,2′,4′-trihydroxychalcone (4) and (±)-4,2′,4′-trihydroxy-3′-{2-hydroxy-2-[tetrahydro-2-methyl-5-(1-methylethenyl)-2-furanyl]ethyl}chalcone (5) were isolated from the aerial parts of Angelica keiskei (Umbelliferae), together with six known compounds: (R)-O-isobutyroyllomatin (2), 3′-O-methylvaginol (3), (?)-jejuchalcone F (6), isoliquiritigenin (7), davidigenin (8), and (±)-liquiritigenin (9). The structures of the new compounds were determined by interpretation of their spectroscopic data including 1D and 2D NMR data. All known compounds (2, 3, and 6–9) were isolated as constituents of A. keiskei for the first time. To identify novel hepatocyte proliferation inducer for liver regeneration, 1–9 were evaluated for their cell proliferative effects using a Hep3B human hepatoma cell line. All isolates exhibited cell proliferative effects compared to untreated control (DMSO). Cytoprotective effects against oxidative stress induced by glucose oxidase were also examined on Hep3B cells and mouse fibroblast NIH3T3 cells and all compounds showed significant dose-dependent protection against oxidative stress.     

Trichodiene biosynthesis and the stereochemistry of the enzymatic cyclization of farnesyl pyrophosphate

Cyclization of trans,trans-[1-³H₂,12,13-¹⁴C]farnesyl pyrophosphate (2a) by a preparation of trichodiene synthetase isolated from the fungus, Trichothecium roseum, gave trichodiene (5a), which was shown by chemical degradation to retain both tritium atoms of the precursor at C-11. Incubation of 1S-[1-³H,12,13-¹⁴C]farnesyl pyrophosphate (2b) and 1R-[1-³H,12,13-¹⁴C]farnesyl pyrophosphate (2c) with trichodiene synthetase and degradation of the resulting labeled trichodienes, 5b and 5c, established that the displacement of the pyrophosphate moiety from C-1 of the precursor and formation of the new C-C bond in the formation of trichodiene takes place with net retention of configuration. These results are accounted for by an isomerization-cyclization mechanism involving the intermediacy of nerolidyl pyrophosphate (4).