Geranyl flavonoids from the leaves of Artocarpus altilis

Five geranyl dihydrochalcones, 1-(2,4-dihydroxyphenyl)-3-{4-hydroxy-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d]pyran-5-yl}-1-propanone (2), 1-(2,4-dihydroxyphenyl)-3-[3,4-dihydro-3,8-dihydroxy-2-methyl-2-(4-methyl-3-pentenyl)-2H-1-benzopyran-5-yl]-1-propanone (4), 1-(2,4-dihydroxyphenyl)-3-[8-hydroxy-2-methyl-2-(3,4-epoxy-4-methyl-1-pentenyl)-2H-1-benzopyran-5-yl]-1-propanone (5), 1-(2,4-dihydroxyphenyl)-3-[8-hydroxy-2-methyl-2-(4-hydroxy-4-methyl-2-pentenyl)-2H-1-benzopyran-5-yl]-1-propanone (8), and 2-[6-hydroxy-3,7-dimethylocta-2(E),7-dienyl]-2',3,4,4'-tetrahydroxydihydrochalcone (9), along with four known geranyl flavonoids (1, 3, 6, 7), were isolated from the leaves of Artocarpus altilis. Their structures were established by spectroscopic means and by comparison with the literature values. Compounds 2, 4, and 9 exhibited moderate cytotoxicity against SPC-A-1, SW-480, and SMMC-7721 human cancer cells.     

Effects of various radicinin analogs on pulse amplitude and arterial blood pressure

The action of some radicinin analogues on the pulse amplitude in urethane anesthetized rats has been studied. The compounds used are:2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (I); 2,3-dihydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (II) 7,8-dihydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (III) 2,3,7,8-tetrahydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione(IV); 2,3,7,8,4',8'-hexahydro-2,7-dimethyl-4H,5H-pyrano[4, 3-b]pyran-4,5-dione (V); 3-crotonyl-4-hydroxy-6-methyl-2H-pyran-2-one (VI); 3-hexanoyl-4-hydroxy-6-methyl-2H-pyran-2-one (VII); 3-hexanoyl-5,6-dihydro-4-hydroxy-6-methyl-2H-pyran-2-one (VIII). A clear increase in the pulse has been seen with the compounds (II), (V) and (VII) especially at the lowest doses, while a decrease in the pulse is caused by the compounds (I) and (VIII). The studied substances have no effects on systolic blood pressure in normotensive unanesthetized rats.     

Phenanthrenoids from the wetland Juncus acutus

Nine 9,10-dihydrophenanthrenes, three phenanthrenes and a related pyrene have been isolated from the wetland plant Juncus acutus. The structures have been attributed by means of their spectral data and chemical correlation. 5-(1-Ethoxy-ethyl)-2-hydroxy-7-methoxy-1,8-dimethyl-9,10-dihydrophenanthrene and 5-(1-phytoxy-ethyl)-2-hydroxy-7-methoxy-1,8-dimethyl-9,10-dihydrophenanthrene, 2,7-dihydroxy-1-methyl-5-vinylphenanthrene, 2,7-dimethoxy-1,6-dimethyl-5-vinylphenanthrene and 2,7-dihydroxy-1,6-dimethylpyrene are described for the first time. Many of the compounds showed in vitro phytotoxicity against Selenastrum capricornutum, a microalga used in aquatic tests.     

Chromenes of polyketide origin from Peperomia villipetiola

An extract of leaves and stems of Peperomia villipetiola has been found to contain myristicin (3-methoxy-4,5-methylenedioxy-allylbenzene) and seven chromenes, whose structures are methyl 5-hydroxy-7-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (1), methyl 5-methoxy-7-methyl-2,2-dimethyl-2H-1-chromene-8-carboxylate (2), methyl 7-hydroxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (3), methyl 7-methoxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (4), 5-methanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (5), 5-methanol-7-methoxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (6), and methyl 5-acetoxymethanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate (7). A biosynthetic rationale for 1-7 suggests that orsellinic acid may be a common intermediate. The anti-fungal activities of the chromenes were measured bioautographically against Cladosporium cladosporioides and Cladosporium sphaerospermum: compounds 6 and 7 were found to be the most active.     

Homoisoflavonoids from Ophiopogon japonicus Ker-Gawler

From the ethyl acetate extract of the tuberous roots of Ophiopogon japonicus (Liliaceae) eight known and five new homoisoflavonoidal compounds were isolated. The new compounds are 5,7-dihydroxy-8-methoxy-6-methyl-3-(2'-hydroxy-4'-methoxybenzyl)chroman-4-one (1), 7-hydroxy-5,8-dimethoxy-6-methyl-3-(2'-hydroxy-4'-methoxybenzyl)chroman-4-one (2), 5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxy-3'-methoxybenzyl)chroman-4-one (3), 2,5,7-trihydroxy-6,8-dimethyl-3-(3',4'-methylenedioxybenzyl)chroman-4-one (4) and 2,5,7-trihydroxy-6,8-dimethyl-3-(4'-methoxybenzyl)chroman-4-one (5). Their structures have been elucidated by mass and NMR spectroscopy. Compounds 4 and 5 are the first isolated homoisoflavonoids with a hemiacetal function at position 2.     

Antiparasitic activity of prenylated benzoic acid derivatives from Piper species

Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC₅₀ 6.5 μg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC₅₀ 3.2 μg/ml) and trypanocidal (16.5 μg/ml) activities, respectively.     

Geranylated flavanones from the secretion on the surface of the immature fruits of Paulownia tomentosa

Chemical investigation of the methanol extract of the viscous secretion on the surface of immature fruits of Paulownia tomentosa furnished nine geranylated flavanones, 6-geranyl-5,7-dihydroxy-3',4'-dimethoxyflavanone (1), 6-geranyl-3',5,7-trihydroxy-4'-methoxyflavanone (2), 6-geranyl-4',5,7-trihydroxy-3',5'-dimethoxyflavanone (3), 6-geranyl-4',5,5',7-tetrahydroxy-3'-methoxyflavanone (4), 6-geranyl-3,3',5,7-tetrahydroxy-4'-methoxyflavanone (5), 4',5,5',7-tetrahydroxy-6-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]-3'-methoxyflavanone (6), 3,3',4',5,7-pentahydroxy-6-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]flavanone (7), 3,3',4',5,7-pentahydroxy-6-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]flavanone (8), and 3,4',5,5',7-pentahydroxy-3'-methoxy-6-(3-methyl-2-butenyl)flavanone (9), along with six known geranylated flavanones. Among these, compounds 4, 6-9 and the known 6-geranyl-3',4',5,7-tetraahydroxyflavanone (diplacone), 6-geranyl-3,3',4',5,7-pentahydroxyflavanone (diplacol) and 3',4',5,7-pentahydroxy-6-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]flavanone showed potent radical scavenging effects towards DPPH radicals.     

Anthrasesamone F from the seeds of black Sesamum indicum

A new anthraquinone derivative, named anthrasesamone F, was isolated from the seeds of Sesamum indicum. Its structure was determined to be (Z)-6,7-dihydroxy-2-(6-hydroxy-4-methyl-3-pentenyl)anthraquinone on the basis of spectroscopic evidence.     

Benzophenones of Garcinia pseudoguttifera (Clusiaceae)

Four biogenetically related benzophenones have been isolated from the Fijian Garcinia pseudoguttifera. They are: 6-hydroxy-2,4-dimethoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (myrtiaphenone-A); 2,2-dimethyl-8-benzoyl-7-hydroxy-5-methoxy-6-(3-methyl-2-butenyl)benzopy ran (myrtiaphenone-B); 2,6-dihydroxy-4-methoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (vismiaphenone-C) and a new benzophenone, 2,2-dimethyl-8-benzoyl-3,7-dihydroxy-5-methoxy- 6-(3-methyl-2-butenyl)-3,4-dihydrobenzopyran (pseudoguttiaphenone-A). Pseudoguttiaphenone-A could be biogenetically derived from vismiaphenone-C. The major component of G. pseudoguttifera was identified as eupha-8,24-dien-3 beta-ol.     

Two diastereomeric saponins with cytotoxic activity from Albizia julibrissin

Two diastereomeric saponins, julibrosides J1 (1) and J9 (2), both of which show cytotoxic activity, were obtained from the stem bark of Albizia julibrissin Durazz. On the basis of chemical and spectral evidence [L.B. Ma et al., Carbohydr. Res., 281 (1996) 35-46], the structure of 1 was revised as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6) -beta-D-glucopyranosyl]-21-O-[(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O- [4-O-((6R)-2-trans-2,6-dimethyl-6-O-(beta-D-quinovopyranosyl)-2,7- octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl] acacic acid-28-O-beta-D-glucopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->4 )]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester. The diastereoisomer 2 of 1 was identified as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6) -beta-D-glucopyranosyl]-21-O-[(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O- [4-O-((6S)-2-trans-2,6-dimethyl-6-O-(beta-D-quinovopyranosyl)-2,7- octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl] acacic acid-28-O-beta-D-glucopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->4 )]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester. Saponin 2 is a new saponin named julibroside J9. Both julibrosides J1 and J9 show good inhibitory action against the KB cancer cell line in vitro.     

Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis

Antifungal activity guided fractionation of the n-butanol extract from the methanol extract of the leaves of Artocarpus nobilis furnished 2',4',4-trihydroxy-3'-geranylchalcone (1), 2 ',4',4-trihydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (2), 2',4',4-trihydroxy-3'-[2-hydroxy-7-methyl-3-methylene-6-octaenyl]chalcone (3), 2',3,4,4'-tetrahydroxy-3'-geranylchalcone (4), 2',3,4,4'-tetrahydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (5). The chalcones 3 and 5 are new natural products whereas 1 and 2 are reported first time from the family Moraceae. All these compounds showed good fungicidal activity against Cladosporium cladosporioides and high radical scavenging activity towards the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical in TLC bio-autography method.     

Anthrasesamone F from the Seeds of Black Sesamum indicum

A new anthraquinone derivative, named anthrasesamone F, was isolated from the seeds of Sesamum indicum. Its structure was determined to be (Z)-6,7-dihydroxy-2-(6-hydroxy-4-methyl-3-pentenyl)anthraquinone on the basis of spectroscopic evidence.     

Laurentixanthones A and B, antimicrobial xanthones from Vismia laurentii

A phytochemical investigation of the constituents of the roots of Vismia laurentii has resulted in the isolation of two xanthone derivatives named laurentixanthone A (1) (6-hydroxy-3,3-dimethyl-11-(3-methylbut-2-enyl)pyrano[2,3-c]xanthen-7(3H)-one) and laurentixanthone B (2) (1-hydroxy-5,6,7,8-tetramethoxyxanthone), along with 11 known compounds: 1,7-dihydroxyxanthone, vismiaquinone, vismiaquinone B, bivismiaquinone, 3-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone, O(1)-demethyl-3',4'-deoxypsorospermin-3',4'-diol, 6-deoxyisojacareubin, 1,8-dihydroxy-6-methoxy-3-methylanthraquinone, kaempferol, friedelin and stigmasterol. The structures of compounds were established by means of spectroscopic methods. Furthermore, the compounds were screened for antimicrobial activities in vitro.     

Phenolic derivatives from Wigandia urens with weak activity against the chemokine receptor CCR5

Three compounds, 2,3-dihydroxy-4-methoxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran (1), 8-methoxy-2-methyl-2-(4-methyl-3-pentenyl)-2H-1-benzopyran-6-ol (2) and 4-methoxy-3-(3-methyl-2-butenyl)-benzoic acid (3), have been isolated from Wigandia urens. The structures of compounds 1, 2 and 3 were determined from spectroscopic data and showed activity in a CCR5 assay with IC(50) values of 33, 46 and 26 muM respectively.     

Simple 1,4-benzoquinones with antibacterial activity from stems and leaves of Gunnera perpensa

From the dichloromethane extract of the leaves and stems of Gunnera perpensa two new, simple 1,4-benzoquinones and a known benzopyran-6-ol were isolated. From the methanol extract phytol was obtained. The two benzoquinones, 2-methyl-6-(-3-methyl-2-butenyl)benzo-1,4-quinone (1) and 3-hydroxy-2-methyl-5-(3-methyl-2-butenyl)benzo-1,4-quinone (2) and the benzopyran, 6-hydroxy-8-methyl-2,2-dimethyl-2H-benzopyran (3) were examined for antimicrobial properties together with the crude stem, leaf and root extracts. Minimum inhibitory concentration (MIC) assays were used to quantify antimicrobial activity and the MIC values for the crude extracts of stems, roots and leaves ranged between 100 microg and >16 mg/ml against the eight microorganisms investigated. Compound 1 showed significant antimicrobial activity with the most sensitive organism being Staphylococcus epidermidis with an MIC of 9.8 microg/ml. For compound 2, no activity was noted. Compound 3 exhibited good activity against the yeasts Cryptococcus neoformans (75 microg/ml) and Candida albicans (37.5 microg/ml).     

Identification and biological evaluation of grapefruit oil components as potential novel efflux pump modulators in methicillin-resistant Staphylococcus aureus bacterial strains

Methicillin-resistant Staphylococcus aureus (MRSA) and MSSA strains were treated with: (a) grapefruit oil (GFO) components, isolated by chromatography and characterised by NMR and mass spectroscopy; (b) antimicrobial agents, or (c) a combination of both to evaluate (MIC determination) intrinsic antibacterial activity and to determine whether GFO components could modulate bacterial sensitivity to the anti-bacterial agents. Preliminary data suggested that the grapefruit component 4-[[(E)-5-(3,3-dimethyl-2-oxiranyl)-3-methyl-2-pentenyl]oxy]-7H-furo[3,2-g]chromen-7-one (2) enhances the susceptibility of test MRSA strains to agents, e.g., ethidium bromide and norfloxacin, to which these micro-organisms are normally resistant.     

Microbial transformation of geraniol and nerol by Botrytis cinerea

Summary Biotransformation of geraniol 1A and nerol 1B was studied with four strains of Botrytis cinerea and three growth media. Using grape must predominant conversion of 1A/1B to E-3,7-dimethyl-2-octen-1,8-diol 5 and 2Z,6E-3,7-dimethyl-2,6-octadien-1,8-diol 16B was observed. However, with one strain and 1A, E-2-methyl-2-hepten-6-one-1-ol 2B, 7-hydroxy-6-methyl-2-heptanone 3 and p-menth-1-ene-9-ol 7 were identified as major metabolites. As further fungal bioconversion products of 1A/1B were detected: Z-2-methyl-2-hepten-6-one-1-ol 2A, 2E,6Z-, 2E,6E-and 2Z,6Z-3,7-dimethyl-2,6-octadien-1,8-diol 4A/4B/16A, Z-3,7-dimethyl-2-octen-1,8-diol 17, 3,7-dimethyl-1,8-octandiol 6, 2E,6E-8-hydroxy-2,6-dimethyl-2,6-octadienal 8, geranial and neral 9, 18, citronellol 10, Z- and E-2,6-dimethyl-2,7-octadien-1,6-diol 13A/13B, 6-hydroxy-2,6-dimethyl-2,7-octadienal 14 as well as 2,6-dimethyl-7-octen-1,6-diol 15. Using synthetic growth medium again -hydroxylation reactions were observed, but 2-methyl-2-hepten-6-one 11 and 7 were also identified as major bioconversion products of 1A and 1B, respectively. Additionally, 2-methyl-2-hepten-6-ol 12 was detected and, using 1B, also traces of 2Z,6E-8-hydroxy-2,6-dimethyl-2,6-octadienal 19 and two 3,9-epoxy-p-menth-1-ene isomers 20A/20B were found. Addition of small amounts of grape must to the synthetic medium (1:700 to 5:700) influenced both the yields of metabolites and their qualitative and quantitative distribution. Identifications of biotransformation products of 1A/1B were performed by capillary gas chromatography (HRGC) and coupled HRGC techniques, i.2. on-line-mass spectrometry (HRGC-MS) and-Fourier transform infrared spectroscopy (HRGC-FTIR) after extractive sample preparation.     

Dihydroisocoumarins and phthalide from wood samples infested by fungi

Wood samples, infested by fungi during storage, were shown to contain, besides the known 5-methyl-mellein, additional (3R)-8-hydroxy-3-methyl-3,4-dihydroisocoumarins substituted by 7-methyl, 5-formyl, 5-carboxy, 5-hydroxy, 5-methoxy, 6-methoxy-5-methyl and 6,7-dimethoxy-5-methyl groups, as well as 6-formyl-7-hydroxy-5-methoxy-4-methylphthalide. Several 2-methylchromanones were synthesized in order to show that this class of compounds can be distinguished from 3-methyl-3,4-dihydroisocoumarins by MS.     

Three isoflavanones with cannabinoid-like moieties from Desmodium canum

Three further derivatives of 5,7,2',4'-tetrahydroxy-6-methyl isoflavanone have been isolated from the root extract of Desmodium canum and assigned the structures 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(1a,2,3,3a,8b,8c-hexahydro-6-hydroxy-1,1,3a-trimethyl-1H-4-oxabenzo[f]cyclobut[c,d]inden-7-yl)-4H-1-benzopyran-4-one (1) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(6a,7,8,10a-tetrahydro-3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl)-4H-1-benzopyran-4-one (2) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl) 4H-1-benzopyran-4-one (3). The three compounds and the previously isolated chromene 4 all derive from the geranylated precursor 5 by a series of cannabinoid-like oxidative rearrangements.     

Photooxidation products of 7,12-dimethylbenz[a]anthracene.

The principal products of the photooxidation of 7,12-dimethylbenz[a]-anthracene (DMBA) in aqueous solutions by photooxidation induced by laboratory lighting have been characterized by high performance liquid chromatograms (HPLC), ultraviolet and mass spectrograms and by comparisons with authentic samples. The products identified were the 7,12-epidioxy-7,12-dihydro-7-12-dimethyl-, 7,12-dione, 7-hydroxymethyl-12-methyl-, 12-hydroxymethyl-7-methyl-, 7-formyl-12-methyl-, 12-formyl-7-methyl-, and 12-hydroxy-12-methyl-7-one derivatives of benz[a]-anthracene. The HPLC profile of products is similar to that obtained from oxidation of DMBA by 'one-electron' reagents, singlet oxygen, or liver microsomal metabolism. The first points of attack are the 7- and 12- positions. The mechanism of photooxidation appears to be generation of singlet oxygen by photodynamic effect of DMBA. None of the products is photosensitizing, however.