Bioconversion of 7-Hydroxyflavanone: Isolation, Characterization and Bioactivity Evaluation of Twenty-One Phase I and Phase II Microbial Metabolites

Microbial metabolism of 7-hydroxyflavanone (1) with fungal culture Cunninghamella blakesleeana (ATCC 8688a), yielded flavanone 7-sulfate (2), 7,4'-dihydroxyflavanone (3), 6,7-dihydroxyflavanone (4), 6-hydroxyflavanone 7-sulfate (5), and 7-hydroxyflavanone 6-sulfate (6). Mortierella zonata (ATCC 13309) also transformed 1 to metabolites 2 and 3 as well as 4'-hydroxyflavanone 7-sulfate (7), flavan-4-cis-ol 7-sulfate (8), 2',4'-dihydroxychalcone (9), 7,8-dihydroxyflavanone (10), 8-hydroxyflavanone 7-sulfate (11), and 8-methoxy-7-hydroxyflavanone (12). Beauveria bassiana (ATCC 7159) metabolized 1 to 2, 3, and 8, flavanone 7-O-β-D-O-4-methoxyglucopyranoside (13), and 8-hydroxyflavanone 7-O-β-D-O-4-methoxyglucopyranoside (14). Chaetomium cochlioides (ATCC 10195) also transformed 1 to 2, 3, 9, together with 7-hydroxy-4-cis-ol (15). Mucor ramannianus (ATCC 9628) metabolized 1 in addition to 7, to also 4,2',4'-trihydroxychalcone (16), 7,3',4'-trihydroxyflavanone (17), 4'-hydroxyflavanone 7-O-α-L-rhamnopyranoside (18), and 7,3',4'-trihydroxy-6-methoxyflavanone (19). The organism Aspergillus alliaceus (ATCC 10060) transformed 1 to metabolites 3, 16, 7,8,4'-trihydroxyflavanone (20), and 7-hydroxyflavanone 4'-sulfate (21). A metabolite of 1, flavanone 7-O-β-D-O-glucopyranoside (22) was produced by Rhizopus oryzae (ATCC 11145). Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antimalarial activities against selected organisms. Metabolites 4 and 16 showed weak antileishmanial activity.     

New isoflavones and flavanol from Iris potaninii

Two new isoflavones, 6, 3', 4'-trimethoxy-7, 8, 5'-trihydroxyisoflavone (1), 7, 4'-dimethoxy-8, 3', 5'-trihydroxy-6-O-beta-D-glucopyranosylisoflavone (2), and 5, 3, 3'-trihydroxy-7, 4'-dimethoxyflavanone (3) have been isolated from the underground parts of Iris potaninii along with known isoflavones (4-8) and iriflophenone (9). The structures of the new compounds were determined using NMR and mass spectroscopic methods.     

Microbial metabolism. Part 12. Isolation, characterization and bioactivity evaluation of eighteen microbial metabolites of 4'-hydroxyflavanone

Fermentation of 4'-hydroxyflavanone (1) with fungal cultures, Beauveria bassiana (ATCC 13144 and ATCC 7159) yielded 6,3',4'-trihydroxyflavanone (2), 3',4'-dihydroxyflavanone 6-O-β-D-4-methoxyglucopyranoside (3), 4'-hydroxyflavanone 3'-sulfate (4), 6,4'-dihydroxyflavanone 3'-sulfate (5) and 4'-hydroxyflavanone 6-O-β-D-4-methoxyglucopyranoside (7). B. bassiana (ATCC 13144) and B. bassiana (ATCC 7159) in addition, gave one more metabolite each, namely, flavanone 4'-O-β-D-4-methoxyglucopyranoside (6) and 6,4'-dihydroxyflavanone (8) respectively. Cunninghamella echinulata (ATCC 9244) transformed 1 to 6,4'-dihydroxyflavanone (8), flavanone-4'-O-β-D-glucopyranoside (9), 3'-hydroxyflavanone 4'-sulfate (10), 3',4'-dihydroxyflavanone (11) and 4'-hydroxyflavanone-3'-O-β-D-glucopyranoside (12). Mucor ramannianus (ATCC 9628) metabolized 1 to 2,4-trans-4'-hydroxyflavan-4-ol (13), 2,4-cis-4'-hydroxyflavan-4-ol (14), 2,4-trans-3',4'-dihydroxyflavan-4-ol (15), 2,4-cis-3',4'-dihydroxyflavan-4-ol (16), 2,4-trans-3'-hydroxy-4'-methoxyflavan-4-ol (17), flavanone 4'-O-α-D-6-deoxyallopyranoside (18) and 2,4-cis-4-hydroxyflavanone 4'-O-α-D-6-deoxyallopyranoside (19). Metabolites 13 and 14 were also produced by Ramichloridium anceps (ATCC 15672). The former was also produced by C. echinulata. Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antiprotozoal activities against selected organisms.     

Flavonoids from Andrographis viscosula

Phytochemical investigation of the whole plant of Andrographis viscosula has led to the isolation of three new 2'-oxygenated flavonoids, (2R)-5-hydroxy-7,2',3'-trimethoxyflavanone (1), 7,2',5'-trimethoxyflavone (2), 5,7,2',3'-tetramethoxyflavone (3), and eight known flavones, 5,7,2'-trimethoxyflavone (4), 5,7,2',4',5'-pentamethoxyflavone (5), echioidinin (6), 5,2',6'-trihydroxy-7-methoxyflavone (7), 5-hydroxy-7,2'-dimethoxyflavone (8), echioidin (9), echioidinin 5-O-glucoside (10), and 5,2',6'-trihydroxy-7-methoxyflavone 2'-O-glucoside (11). The structures of 1-11 were elucidated by physical and spectral methods, including extensive 2D NMR studies. The presence of 2'-oxygenated flavonoids is apparently restricted to Andrographis species in Acanthaceae. Therefore, 2'-oxygenated flavonoids are regarded as chemotaxonomic markers of Andrographis genus in the Acanthaceae family.     

A new homostilbene and two new homoisoflavones from the bulbs of Scilla scilloides

A new homostilbene, named scillabene A (2), and two new homoisoflavones, named scillavones A (3) and B (4), were isolated from the bulbs of Scilla scilloides DRUCE (Liliaceae) along with 13 known compounds comprising a homostilbene, seven homoisoflavones, a xanthone, a lignan, and three nortriterpenes. The structures of 2-4 were characterized as 3,5,4'-trihydroxy-3'-methoxy-4-methyl-trans-stilbene, (3R)-5,7,2'-trihydroxy-3',4'-dimethoxyspiro{2H-1-benzopyran-7'-bicyclo[4,2,0]octa[1,3,5]-trien}-4-one and (3S)-3-(3,4-dihydroxybenzyl)-5-hydroxy-6,7-dimethoxychroman-4-one, respectively, on the basis of spectroscopic data and X-ray crystallographic analysis.     

Antioxidant activity and two new flavonoids from Washingtonia filifera

Two new flavonoids, 8-hydroxyisoscoparin (1) and luteolin 7-O-glucoside 4'-sulfate (2), along with eight known flavonoids, including luteolin 7-O-glucoside 2'-sulfate, were isolated and identified from Washingtonia filifera. All compounds were characterized by (1)H-NMR, (13)C-NMR, CI-MS, FABMS and UV. The antioxidant activities of various W. filifera extracts were determined.     

Two New Antibacterial Flavanones from Sophoraflavescens

The dry root of Sophora flavescens, which is a well-known Chinese herbal medicine, has been used for the treatment of diarrhea, gastrointestinal hemorrhage and eczema1. Here we report the structure elucidation of two new flavanones isolated from this plan…     

Allergy-preventive flavonoids from Xanthorrhoea hastilis

Allergy-preventive activity was demonstrated for an extract of resins from Xanthorrhoea hastilis R. BR. in a search for allergy-preventive substances from natural sources. By bioassay-directed fractionation of this plant extract, a new flavanone, 3',5'-dihydroxy-7,4'-dimethoxyflavanone (1), and two new chalcones, 3,5,2'-trihydroxy-4,4'-dimethoxychalcone (2) and 5,2'-dihydroxy-3,4,4'-trimethoxychalcone (3), were isolated together with five known compounds, 5'-hydroxy-7,3',4'-trimethoxyflavanone (4), 3'-hydroxy-7,4'-dimethoxyflavanone (5), liquiritigenin 7-methyl ether (6), 4,2'-dihydroxy-4'-methoxychalcone (7) and sakuranetin (8). The structures of 1, 2 and 3 were elucidated by spectroscopic methods. All of these compounds showed allergy-preventive effects.     

Phenolic compounds and antioxidant activities of Liriope muscari

Five phenolic compounds, namely N-trans-coumaroyltyramine (1), N-trans-feruloyltyramine (2), N-trans-feruloyloctopamine (3), 5,7-dihydroxy-8-methoxyflavone (4) and (3S)3,5,4'-trihydroxy-7-methoxy-6-methylhomoisoflavanone (5), were isolated from the fibrous roots of Liriope muscari (Liliaceae). Compounds 2-5 were isolated for the first time from the Liriope genus. Their in vitro antioxidant activities were assessed by the DPPH and ABTS scavenging methods with microplate assays. The structure-activity relationships of compounds 1-3 are discussed.     

Microbial metabolism part 9. Structure and antioxidant significance of the metabolites of 5,7-dihydroxyflavone (chrysin), and 5- and 6-hydroxyflavones

5,7-Dihydroxyflavone (chrysin) (1) when fermented with fungal cultures, Aspergillus alliaceous (ATCC 10060), Beauveria bassiana (ATCC 13144) and Absidia glauco (ATCC 22752) gave mainly 4'-hydroxychrysin (4), chrysin 7-O-beta-D-4-O-methylglucopyranoside (5) and chrysin 7-sulfate (6), respectively. Mucore ramannianus (ATCC 9628), however, transformed chrysin into six metabolites: 4'-hydroxy-3'-methoxychrysin (chrysoeriol) (7), 4'-hydroxychrysin (apigenin) (4) 3',4'-dihydroxychrysin (luteolin) (8), 3'-methoxychrysin 4'-O-alpha-D-6-deoxyallopyranoside (9), chrysin 4'-O-alpha-D-6-deoxyallopyranoside (10), and luteolin 3'-sulfate (11). Cultures of A. alliaceous (ATCC 10060) and B. bassiana (ATCC 13144) metabolized 5-hydroxyflavone (2) into 5,4'-dihydroxyflavone (12) and 4'-hydroxyflavone 5-O-beta-D-4-O-methylglucopyranoside (13), respectively. 6-Hydroxyflavone (3) was transformed into 6-hydroxyflavanone (14), flavone 3-O-beta-D-4-O-methylglucopyranoside (15) and (+/-)-flavanone 6-O-beta-D-4-O-methylglucopyranoside (16) by cultures of Beauveria bassiana (ATCC 13144). The structures of the metabolic products were elucidated by means of spectroscopic data. The significance of the metabolites as antioxidants in relation to their structure is briefly discussed.     

Microbial metabolism of biologically active secondary metabolites from Nerium oleander L

Ursolic acid (1) and kaempferol (3) are two major constituents of the Mediterranean plant Nerium oleander L. Microbial metabolism of (1) with Aspergillus flavus (ATCC 9170) resulted in the formation of 3-oxo-ursolic acid derivative, ursonic acid (2). On the other hand, Cunninghamella blakesleeana (ATCC 8688A) was able to convert (3) into kaempferol 3-O-beta-D-glucopyranoside (4) as well as the new natural product kaempferol 4'-sulfate (5). Incubation of kaempferol with Mucor ramannianus (ATCC 9628) led to the isolation of one metabolite identified as kaempferol 4'-O-alpha-L-rhamnopyranoside (6). Transformation of kaempferol to the new compound kaempferol 7-O-beta-D-4-O-methylglucopyranoside (7) and herbacetin 8-O-beta-D-glucopyranoside (8) was observed after fermentation with Beauveria bassiana (ATCC 13144). Cytotoxic as well as antioxidant activities of the isolated metabolites were determined.     

Alpha-glucosidase inhibitory constituents from Duranta repens

Three C-alkylated flavonoids 7-O-alpha-D-glucopyranosyl-3,5-dihydroxy-3'-(4"-acetoxyl-3"-methylbutyl)-6,4'-dimethoxyflavone (1), 7-O-alpha-D-glucopyranosyl-3,4'-dihydroxy-3'-(4"-acetoxyl-3"-methylbutyl)-5,6-dimethoxyflavone (2), 3,7,4'-trihydroxy-3'-(8"-acetoxy-7"-methyloctyl)-5,6-dimethoxyflavone (3) and a trans-clerodane type diterpenoid (-)-6beta-hydroxy-5beta,8beta,9beta,10alpha-cleroda-3,13-dien-16,15-olid-18-oic acid (4) are reported from Duranta repens along with (+)-hardwickiic acid (5) and (+)-3,13-clerodadien-16,15-olid-18-oic acid (6), isolated for the first time from this species. Their structures were established on the basis of the spectral methods, especially two dimensional (2D) NMR spectroscopy.     

Studies on the constituents of Scutellaria species (XXII). Constituents of the roots of Scutellaria amabilis HARA

From the roots of Scutellaria amabilis HARA, eleven new flavonoids, 5,7,2'-trihydroxy-8-methoxyflavone 7-O-beta-D-glucopyranoside, 5,7,2'-trihydroxy-8-methoxyflavone 2'-O-beta-D-glucopyranoside, 5,7-dihydroxy-8,2'-dimethoxyflavone 7-O-beta-D-glucopyranoside, 5,7,2'-trihydroxyflavone 2'-O-beta-D-glucopyranoside, 5,7,2',5'-tetrahydroxyflavone 7-O-beta-D-glucuronopyranoside, (2S)-5,7,2',5'-tetrahydroxyflavanone, (2S)-5,7,2',5'-tetrahydroxyflavanone 7-O-beta-D-glucopyranoside, (2S)-5,7,2',5'-tetrahydroxyflavanone 7-O-beta-D-glucuronopyranoside, (2S)-7,2'-dihydroxy-5-methoxyflavanone 7-O-beta-D-glucuronopyranoside, (I-2S)-I-5,II-5,I-7,II-7,I-2',II-2',II-5'-heptahydroxy-[I-6,II-6']-flavanonylflavone and (I-2S)-I-5,II-5,I-7,II-7,I-2',II-2',I-5',II-5'-octahydroxy-[I-6,II-6']-flavanonylflavone, were isolated, together with ten known flavonoids, wogonin (5,7-dihydroxy-8-methoxyflavone), 5,7-dihydroxy-8,2'-dimethoxyflavone, (2S)-5,7,2'-trihydroxyflavanone, scutevulin (5,7,2'-trihydroxy-8-methoxyflavone), 5,7,4'-trihydroxy-8-methoxyflavone, alpinetin ((2S)-7-hydroxy-5-methoxyflavanone), 5,7,2'-trihydroxyflavone, 5,7,2',5'-tetrahydroxyflavone, (2S)-7,2'-dihydroxy-5-methoxyflavanone and 5,7-dihydroxy-8,2'-dimethoxyflavone 7-O-beta-D-glucuronopyranoside. The structures were determined on the basis of chemical and spectral data.     

Two new 2'-oxygenated flavones from Andrographis elongata.

Two new 2'-oxygenated flavones, 5,2',6'-trihydroxy-7-methoxyflavone (3) and skullcapflavone I 2'-O-beta-D-(4"-E-cinnamyl) glucopyranoside (5), together with three known flavones, 7-O-methylwogonin (1), skullcapflavone I (2) and skullcapflavone I 2'-O-beta-D-glucopyranoside (4) were isolated from the whole plant of Andrographis elongata, and the structures were elucidated by FAB-MS and one- and two-dimensional (1D- and 2D)-NMR spectral studies including 1H-1H correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond connectivity (HMBC) and rotating frame Overhauser enhancement spectroscopy (ROESY) experiments, and chemical studies.     

Studies on the constituents of Lagochilus leiacanthus (Labiatae)

Two flavanones, 5,2',6'-trihydroxy-7,8-dimethoxyflavanone (1), 5,2',6'-trihydroxy-6,7,8-trimethoxyflavanone (2) and their 2'-O-β-D-glucosides (3, 4), and a neoclerodane-type diterpene, 15-demethoxyscupolin I (5), together with twenty-eight known compounds were isolated from the extracts of Lagochilus leiacanthus. The structures of the new compounds were determined by spectroscopic means. The two new flavanones and some known flavonoids showed the inhibitory activity on the release of β-hexosaminidase from RBL-2H3 cells.     

New constituents from Crinum latifolium with inhibitory effects against tube-like formation of human umbilical venous endothelial cells

Six compounds (1-6) were isolated from the methanol extract of Crinum latifolium by bioassay-guided separation. Among the six isolates, compounds 2 and 6 were new metabolites. Their structures were established as 4-senecioyloxymethyl-3,4-dimethoxycoumarin (2) and 5,6,3'-trihydroxy-7,8,4'-trimethoxyflavone (6) based on spectroscopic analyses. Compound 2 was found to be strongly inhibitory against the in vitro tube-like formation of human umbilical venous endothelial cells (HUVECs) while manifesting no cytotoxicity in tumor cell lines (B16F10, HCT116). Significant inhibitory activity (inhibition percentage, 53.5%) was still observed at concentrations as low as 1 microg/mL. Compound 6 showed a modest inhibitory effect on the tube-like formation of HUVECs. Other compounds, including cycloartenol (1), 4',7-dihydroxy-3'-methoxyflavan (3), 4',7-dihydroxyflavan (4), and 2',4',7-trihydroxydihydrochalcone (5) were found to be nearly inactive.     

NMR spectral assignments of a new [C--O--C] isoflavone dimer from Andira surinamensis

The phytochemical investigation of extracts from the branch wood and branch barks of Andira surinamensis yielded a novel isoflavone dimer, 4'-methoxyisoflavone-(7-O-7')-3',4'-methylenedioxyisoflavone (surinamensin), along with the triterpene lupeol and the known isoflavones 5,7-dihydroxy-4'-methoxyisoflavone (biochanin A), 5,4'-dihydroxy-7-methoxyisoflavone (prunetin), 7,3'-dihydroxy-4'-methoxyisoflavone (calycosin), and 5,7,3'-trihydroxy-4'-methoxyisoflavone (pratensein). The structure of the new isoflavone was elucidated by 1D and 2D homonuclear and heteronuclear NMR spectroscopy and by comparison with published data for closely related compounds.     

Structure of new carotenoids with a 3,4-dihydroxy-beta-end group from the oyster Crassostrea gigas

Three new carotenoids with a 3,4-dihydroxy-beta-end group were isolated from the oyster Crassostrea gigas. These structures were determined to be 3,4,3',8'-tetrahydroxy-beta,kappa-caroten-6'-one (1), 3,4-dihydroxy-3',6'-epoxy-1',2',5',6'7',8'-hexahydro-6'-methyl-16'-nor-beta,-carotene-1',8'-dione (2), and 3,6-epoxy-5,3',4'-trihydroxy-12',13',20'-trinor-beta,beta-caroten-19,11-olide (3) based on chemical and spectral data.     

A new benzophenone C-glycoside from Polygala telephioides Willd

<正>A new benzophenone C-glucoside,3'-C-[4-O-(5-hydroxyferuloyl)-β-D-glucopyranosyl]-2′,4′,6′-trihydroxy-3,4-dimethoxy-benzophenone, named telephenone D,was isolated from the whole plants of Polygala telephioides,and its structure was determined by analysis of spectroscopic data.     

Schoepfin A, B, C: three new chalcone C-glycosides from Schoepfia chinensis

Three new chalcone C-glycosides named schoepfin A, B, C (1-3), together with three known compounds 4,2',4'-trihydroxy-3'-C-beta-D-glucosylchalcone (4), nothofagin (5) and hemiphloin (6) were isolated from ethanolic extract of the bark of Schoepfia chinensis Gardn. et Champ (Olacaceae). Their structures were determined mainly by spectroscopic techniques including 2D-NMR (HMBC, HMQC) and MS experiments.