Three new oblongolides from Phomopsis sp. XZ-01, an endophytic fungus from Camptotheca acuminate

Four new metabolites, including three new oblongolides named C1, P1, and X1 (1-3) and 6-hydroxyphomodiol (10), along with eight known compounds--oblongolides B (4), C (5), D (6), O (7), P (8) and U (9), (3R,4aR,5S,6R)-6-hydroxy-5-methylramulosin (11), and (3R)-5-methylmellein (12)--were isolated from the endophytic fungal strain Phomopsis sp. XZ-01 of Camptotheca acuminate. Their structures were elucidated by spectroscopic analyses, including 1H- and 13C-NMR, 2D NMR (HSQC, HMBC, 1H-1H COSY and NOESY) and HR-FT-MS. Cytotoxic activities of these compounds were evaluated. Some of them showed weak selective activities.     

Preparation of carbocyclic S-adenosylazamethionine accompanied by a practical synthesis of (-)-aristeromycin

For the preparation of a carbocyclic nitrogen analogue of S-adenosylmethionine (carba-AdoazaMet, 4), a practical synthesis of (-)-aristeromycin (7) has been developed using variations of literature procedures. This approach called for a stereospecific synthesis of (3aR,6aR)-2,2-dimethyl-3a,6a-dihydrocyclopenta[1,3]dioxol-4-one ((4R, 5R)-4,5-O-isopropylidene-2-cyclopentenone) (8), which was achieved by modifying reported procedures from D-(-)-ribose.     

Verpacamides A-D, a sequence of C11N5 diketopiperazines relating cyclo(Pro-Pro) to cyclo(Pro-Arg), from the marine sponge Axinella vaceleti: possible biogenetic precursors of pyrrole-2-aminoimidazole alkaloids

[reaction: see text] Four C(11)N(5) diketopiperazine metabolites named verpacamides A (6), B (7), C (8), and D (9) consisting of a proline-arginine dipeptide skeleton have been isolated from the marine sponge Axinella vaceleti. Verpacamides A-D are a sequence of metabolites showing the transformation of proline and arginine into the oxidized guanidinyl-cyclo(Pro-Pro) 8 and 9. Compounds 6-9 are structurally and chemically related to C(11)N(5) pyrrole-2-aminoimidazole metabolites also isolated from the Axinellidae and Agelasidae families of sponges and exemplified by dispacamide A (4) and dibromophakellin (10).     

Terpenoids and phenolics from Plectranthus strigosus, bioactivity screening

Further studies on Plectranthus sp. (Lamiaceae) led to the isolation of terpenes and phenol esters from Plectranthus strigosus Benth. ent-16-Kauren-19-ol (1), ent-16-kauren-19-oic acid (2), xylopic acid (3), xylopinic acid (4), hinokiol (5), 4 beta,6 beta-dihydroxy-1 alpha,5 beta(H)-guai-9-ene (6) 4 beta,6 beta-dihydroxy-1 alpha,5 beta(H)-guai-10(14)-ene (7), mixtures of hexacosan-1,26-diol and octacosan-1,28-diol ferulate diesters (8), of esters from ferulic acid and fatty alcohols (9) and of esters from fatty acids and 2-(4-hydroxyphenyl)-ethanol (10) were for the first time isolated from this genus. Supplementary spectral data for 3,8 and parvifloron D (11) metabolites are also presented. A bioactivity study revealed herpetic inhibitory properties for (1) and (2), and antioxidant ability for (5) and (8) phenolic constituents.     

Eleven new 2-pyrones from a Fungi Imperfecti, Trichurus terrophilus, found in a screening study guided by immunomodulatory activity

In a screening study on immunomodulatory fungal constituents, eleven new 2-pyrones tentatively named TT-1 (1), and TT-2-11 (2-11) have been isolated from a Fungi Imperfecti, Trichurus terrophilus, and designated rasfonin (1), and trichurusin B-K (2-11), respectively. Compounds 1-4 exhibited considerably high immunosuppressive activities, and compounds 8-11 have shown moderate ones. The structure-activity relationships of these constituents have also been discussed.     

Isolation, structure elucidation, and biological activity of a new alkaloid from Zanthoxylum rhetsa

Several biologically active alkaloids (1-4, 6), including a new quinazoline-6-carboxylic acid (1), were isolated from the medicinal plant Zanthoxylum rhetsa, an evergreen tree, native to subtropical areas. Whereas the pharmacological properties of the plant extract and single constituents have been widely tested, we now show that all of the metabolites have antialgal activities, all but 6 are antibacterial, and 6 and the reduction product 5 (derived from 4) are also antifungal.     

Indonesian medicinal plants. XXIII. Chemical structures of two new migrated pimarane-type diterpenes, neoorthosiphols A and B, and suppressive effects on rat thoracic aorta of chemical constituents isolated from the leaves of Orthosiphon aristatus (Lamiaceae)

Two novel migrated pimarane-type diterpenes named neoorthosiphols A (1) and B (2) were isolated from the water decoction of the leaves of Orthosiphon aristatus (Lamiaceae), which has been prescribed in Javanese traditional medicine (jamu) for the treatment of hypertension, etc. The absolute chemical structures have been elucidated on the basis of physicochemical properties. It has been found that two migrated pimarane-type diterpenes (1, 2), four isopimarane-type diterpenes (3, 4, 5, 6), three benzochromenes (7, 8, 9) and two flavones (12, 13) exhibit a suppressive effect on contractile responses in rat thoracic aorta, among thirteen chemical constituents (1-13) isolated from the leaves.     

Enantiospecific synthesis of polhydroxylated indolizidines related to castanospermine: 1 (6R,7S,8aR)-6,7-dihydroxyindolizidine and (6R,7R,8S,8aR)-6,7,8-trihydroxyindolizidine.

Enantiospecific syntheses of (6R,7S,8aR)-6,7-dihydroxy-indolizidine (3) and (6R,7R,8S,8aR)-6,7,8-trihydroxy-indolizidine (4) from methyl 2-azido-4,6-O-benzylidene-2-deoxy-α-D-altropyranoside (7) are reported. The two synthetic indolizidines (3) and (4) have been tested against a wide range of enzymes.     

Studies on the metabolism of gomisin A (TJN-101). II. Structure determination of biliary and urinary metabolites in rat

After oral administration of gomisin A (1) to rats, the bile and urine were collected and treated with beta-glucuronidase and arylsulfatase. Seven metabolites, met B (2), met A-III (3), met E (4), met D (5), met F (6), met G (7), and met H (8) were isolated from the bile treated with the enzymes. Eight metabolites 2-8, and met A-II (9) were isolated from the urine treated with the enzymes. A major metabolite 2, and two minor metabolites 3 and 9 were identified as met B, met A-III, and met A-II, respectively, which are oxidative products of 1 formed by rat liver S9 mix. The structures of five new metabolites 4-7, and 8 were determined on the basis of chemical and spectral studies.     

Beta-orcinol metabolites from the lichen Hypotrachyna revoluta

Four new beta-orcinol metabolites, hypotrachynic acid (1), deoxystictic acid (2), cryptostictinolide (3) and 8'-methylconstictic acid (4) along with the metabolites 8'-methylstictic acid (5), 8'-methylmenegazziaic acid (6), stictic acid (7), 8'-ethylstictic acid (8) and atranorin (9), that have been previously described, were isolated for the first time from the tissue extracts of the lichen Hypotrachyna revoluta (Fl?rke) Hale. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analyses. Radical scavenging activity (RSA) of the metabolites isolated in adequate amounts, was evaluated using luminol chemiluminescence and comparison with Trolox.     

Phenylpropanoid glycosides from Rhodiola rosea

Rhodiola rosea L. (Golden Root) has been used for a long time as an adaptogen in Chinese traditional medicine and is reported to have many pharmacological properties. Along its known secondary metabolites tyrosol (1), salidroside (rhodioloside) (2), rosin (3), rosarin (4), rosavin (5), sachaliside 1 (6) and 4-methoxy-cinnamyl-O-beta-D-glucopyranoside (7), four compounds were isolated from aqueous methanol extract of the plant and identified as cinnamyl-(6'-O-beta-xylopyranosyl)-O-beta-glucopyranoside (8), 4-methoxy-cinnamyl-(6'-O-alpha-arabinopyranosyl)-O-beta-glucopyranoside (9), picein (10) and benzyl-O-beta-glucopyranoside (11) by UV, MS and NMR methods. Compounds 8 and 9 are new natural compounds whereas compounds 10 and 11 were isolated first time from R. rosea. Also the compounds 6 and 7 are isolated earlier only from the callus cultures of the plant but not from the differentiated plant.     

Synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans

The N-phenethyl analogues of (1R*,4aR*,9aS*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-6-ol and 8-ol and (1R*,4aR*,9aR*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2.3-c]pyridin-6-ol and 8-ol, the ortho- (43) and para-hydroxy e- (20), and f-oxide-bridged 5-phenylmorphans (53 and 26) were prepared in racemic and enantiomerically pure forms from a common precursor, the quaternary salt 12. Optical resolutions were accomplished by salt formation with suitable enantiomerically pure chiral acids or by preparative HPLC on a chiral support. The N-phenethyl (-)- para-e enantiomer (1S,4aS,9aR-(-)-20) was found to be a mu-opioid agonist with morphine-like antinociceptive activity in a mouse assay. In contrast, the N-phenethyl (-)-ortho-f enantiomer (1R,4aR,9aR-(-)-53) had good affinity for the mu-opioid receptor (K(i) = 7 nM) and was found to be a mu-antagonist both in the [(35)S]GTP-gamma-S assay and in vivo. The molecular structures of these rigid enantiomers were energy minimized with density functional theory at the level B3LYP/6-31G* level, and then overlaid on a known potent mu-agonist. This superposition study suggests that the agonist activity of the oxide-bridged 5-phenylmorphans can be attributed to formation of a seven membered ring that is hypothesized to facilitate a proton transfer from the protonated nitrogen to a proton acceptor in the mu-opioid receptor.     

A chemical study of burley tobacco flavour (Nicotiana tabacum L.) VI. Identification and synthesis of four irregular terpenoids related to solanone, including a 'prenylsolanone'.

Four novel constituents of Burley tobacco condensate have been identified as (E)-5-isopropyl-7-(2-methyl-tetrahydrofur-2-yl)-hept-6-en-2-one ( G ), (E)-5-isopropyl-7-(2-methyl-tetrahydrofur-2-yl)-hept-6-en-2-ol ( H ), (E)-4-methyl-7-isopropyl-10-oxo-undec-5-en-4-olide ( I ), and (E, E)-6,12-dimethyl-9-isopropyltrideca-5,10,12-trien-2-one ( J ) or ‘prenylsolanone’. Compounds G , H , and I were synthesized from norsolanadione ( 1 ), compound J from solanone ( A ). These substances belong to a growing family of tobacco metabolites structurally related to solanone ( A ). Their possible formation from cembrene-type precursors is briefly outlined.     

Synthesis of rac-(1R,4aR,9aR)-2-methyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-6-ol. An unusual double rearrangement leading to the ortho- and para-f oxide-bridged phenylmorphan isomers

In an attempt to obtain the para-f isomer, rac-(1R,4aR,9aR)-2-methyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-6-ol, via mesylation of an intermediate 9[small alpha]-hydroxyphenylmorphan, we obtained, instead, a rearranged chloro compound with a 5-membered nitrogen ring, 7-chloro-3a-(2,5-dimethoxyphenyl)-1-methyl-octahydroindole. This indole underwent a second rearrangement to give us the desired para-f isomer. The structures of the intermediate indole and the final product were unequivocally established by X-ray crystallography. A resynthesis of the known rac-(1R,4aR,9aR)-2-methyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-8-ol, the ortho-f isomer, was achieved using the reaction conditions for the para-f isomer, as well as under Mitsunobu reaction conditions where, unusually, the oxide-bridge ring in the 5-phenylmorphan was closed to obtain the desired product. The synthesis of the para-f isomer adds an additional compound to those oxide-bridged phenylmorphans that were initially visualized and synthesized; the establishment of the structure and configuration of 8 of the theoretically possible 12 racemates has now been achieved. The X-ray crystallographic structure analysis of the para-f isomer provides essential data that will be needed to establish the configuration of a ligand necessary to interact with an opioid receptor.     

Microbial metabolism. Part 6. Metabolites of 3- and 7-hydroxyflavones

Fermentation of 3-hydroxyflavone (1) with Beauveria bassiana (ATCC 13144) yielded 3,4'-dihdroxyflavone (3), flavone 3-O-beta-D-4-O-methylglucopyranoside (4) and two minor metabolites. 7-Hydroxyflavone (2) was transformed by Nocardia species (NRRL 5646) to 7-methoxyflavone (5) whilst Aspergillus alliaceus (ATCC 10060) converted it to 4',7-dihydroxyflavone (6). Flavone 7-O-beta-D-4-O-metylglucopyranoside (7) and 4'-hydroxyflavone 7-O-beta-D-4-O-methylglucopyranoside (8) were the metabolic products of 7-hydroxyflavone (2) when fermented with Beauveria bassiana (ATCC 7159). One of the minor metabolites of 3-hydroxyflavone (1) was tentatively assigned a beta'-chalcanol structure (9). Compounds 4, 7 and 8 are reported as new compounds. Structure elucidation of the metabolites was based on spectroscopic data.     

New phenolic constituents from the fruit juice of Phyllanthus emblica

Six new phenolic constituents, L-malic acid 2-O- (1), mucic acid 2-O- (5), mucic acid 1,4-lactone 2-O- (6), 5-O- (8), 3-O- (10), and 3,5-di-O- (11) gallates, were isolated from the fruit juice of Phyllanthus emblica together with their methyl esters (2-4, 7, 9), and their structures were determined by spectral and chemical methods. Compounds 5, 6, and 8, the major phenolic constituents of the juice, were present as an equilibrium mixture in aqueous solution.     

Antioxidant, anti-glycation and anti-inflammatory activities of phenolic constituents from Cordia sinensis

Nine compounds have been isolated from the ethyl acetate soluble fraction of C. sinensis, namely protocatechuic acid (1), trans-caffeic acid (2), methyl rosmarinate (3), rosmarinic acid (4), kaempferide-3-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranoside (7), kaempferide-3-O-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside (8) and kaempferol-3-O-α-L-rhamno-pyranosyl (1→6)-β-D-glucopyranoside (9), all reported for the first time from this species. The structures of these compounds were deduced on the basis of spectroscopic studies, including 1D and 2D NMR techniques. Compounds 1-9 were investigated for biological activity and showed significant anti-inflammatory activity in the carrageen induced rat paw edema test. The antioxidant activities of isolated compounds 1-9 were evaluated by the DPPH radical scavenging test, and compounds 1, 2, 4 and 7-9 exhibited marked scavenging activity compared to the standard BHA. These compounds were further studied for their anti-glycation properties and some compounds showed significant anti-glycation inhibitory activity. The purity of compounds 2-5, 8 and 9 was confirmed by HPLC. The implications of these results for the chemotaxonomic studies of the genus Cordia have also been discussed.     

New Monoterpene-Substituted Dihydrochalcones from Piper aduncum

Five New unusual monoterpene-substituted dihydrochalcones, the adunctins A–E (1″S)-1-{2′-hydroxy-4′-methoxy-6′-[4″-methyl-1″-(1?-methylethyl)cyclohex-3″ -en-1″ -yloxy]phenyl}-3-phenylpropan-1-one ( 1 ), (5aR*,8R*,9aR*)-3-phenyl-1-[5′,8′,9′,9′a-tetrahydro-3′-hydroxy-1′-methoxy-8′-(1″-methylethyl)-5′-a-methyldibenzo-[b,d]furan-4′-yl]propan-1-one ( 2 ), (2′R*,4″S*)-1-{6′-hydroxy-4′-methoxy-4″-(1?-methylethyl)spiro[benzo[b]-furan-2′(3′H),1″ -cyclohex-2″ -en]-7′-yl}-3-phenylpropan-1-one ( 3 ), (2′R*,4″R*)-1-{6′-hydroxy-4′-methylethyl-4″-(1?-methylethyl)spiro[benzo[b]furan-2′(3′H),1″-cyclohex-2″-en]-7′-yl}-3-phenypropan-1-one ( 4 ), and (5′aR*,6′S*, 9′R*,9′aS*)-1-[5′a,6′,7′,8′,9′a-hexahydro-3′,6′-methoxy-6′-methyl-9′-(1″-methylethyl)dibenzo[b,d]-furan-4′-yl]-3-phenylpropan-1-one ( 5 ) were isolated from the leaves of Piper aduncum (Piperaceae) by preparative liquid chromatography. In addition, (?)-methyllindaretin ( 6 ), trans-phytol, and α-tocopherol ( = vitamin E) were also isolated and identified. The structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The antibacterial and cytotoxic potentials of the isolates were also investigated.     

Chemical fingerprint analysis and metabolic profiling of 50% ethanol fraction of Lomatogonium rotatum by ultra‐performance liquid chromatography/quadrupole–time of flight mass spectrometry

Lomatogonium rotatum (L.) Fries ex Nym (L. rotatum), a member of Gentianaceae, is an important mongolian medicine in China used to treat febrile diseases in liver and gallbladder. The aim of present study was to investigate the chemical constituents and metabolites of the 50% ethanol fraction of L. rotatum (50EtLR). Firstly, the extract of L. rotatum was partitioned by macroporous resin to obtain the target fraction (50EtLR), then several compounds were isolated from 50EtLR to obtained the standards for further analysis of chemical constituents of 50EtLR. Secondly, the chemical constituents of 50EtLR were characterized using the ultra‐high performance liquid chromatography coupled with quadrupole–time‐of‐flight mass spectrometry (UHPLC–Q‐TOF–MS/MS). Finally, prototype constituents and related metabolites were analyzed after orally administerng 50EtLR to rats. As a result, a new compound, 6‐O‐[β‐d ‐xylopyranosyl‐(1 → 6)‐O‐β‐d ‐glucopyranosyl]‐1,4,8‐trimethoxyxanthone ( 6 ) along with seven known compounds ( 1–5 , 7 and 8 ) were isolated from the 50EtLR, 92 components were either unambiguously or tentatively identified. Additionally, 34 prototype constituents and 112 metabolites in rat plasma along with 32 prototype constituents and 53 metabolites in rat liver were tentatively identified. Therefore, xanthones and flavonoids were the main chemical constituents of 50EtLR and sulfation and glucuronidation are the main enzyme‐induced metabolic pathways involved post‐administration.     

Biotransformation of a C-glycosylflavone, abrusin 2''-O-beta-D-apioside, by human intestinal bacteria

After anaerobic incubation of abrusin 2'-O-beta-D-apioside (1) with a human fecal suspension, five metabolites were isolated and identified as abrusin (2), 1-(2',6'-dihydroxy-3',4'-dimethoxyphenyl)-3-(4'-hydroxyphenyl)propan-1- one (5), 5,6-dimethoxybenzene-1,3-diol (6), 3-(4'-hydroxyphenyl)propionic acid (7) and 3-phenylpropionic acid (8). However, methyl ether derivatives of abrusin (4'-O-methylabrusin and 4'-O-, 5-O-dimethylabrusin) resisted degradation under the same conditions.