Flavonoids and tannins of Acacia species

The heartwoods of Acacia giraffae and A. galpinii were selected from South African Acacias as representative of those with abnormally high and minimal tannin contents respectively. A. galpinii contains amongst other analogues, the first natural (+)-2,3-trans-3,4-trans-teracacidin (7,8,4′-trihydroxy-flavan-3,4-diol and novel 3-O-methyl-, 7,8-di-O-methyl- and 7,8,4′-tri-O-methylflavonol analogues. (−)-2,3-cis-3,4-cis-Melacacidin (7,8,3′,4′-tetrahydroxyflavan-3,4-diol) is also present, but tannins are absent. By contrast, from the large excess of leueofisetinidin tannins which characterizes the wood of A. giraffae, only (+)-catechin, (+)-2,3-trans-3,4-trans-leucofisetinidin (7,3′,4′,trihydroxyflavan-3,4-diol and all-trans-(+)-leueofisetinidin-(+)-catechin could be isolated.     

Synthesis of metabolic intermediates of diethylstilbestrol

This report details the synthesis of 1) 3,4,4′-trihydroxy-α,α′-diethyl-trans-stilbene; 2) 3,4-bis-(p-hydroxyphenyl)-trans-3-hexenol; 3) 3,4-bis-(p-hydroxyphenyl)-2,4-cis,cis-hexadienol; 4) 3,4-bis-(3′-methoxy-4′-hydroxyphenyl)-trans-3-hexene; 5) 3,4-bis-(3′, 4′-dimethoxyphenyl)-trans-3-hexene. These compounds are suspected metabolites of diethylstilbestrol.     

(+)-2,3-Trans-pubeschin,the first catechin analogue of peltogynoids from Peltogyne pubescens and P. venosa

The heartwoods of Peltogyne pubescens and P. venosa contain the predominant pair (+)-peltogynol and (+)-mopanol, their 4-epimers, (+)-peltogynol B and (+)-mopanol B, together with the first catechin analogue of peltogynol, (+)-2,3- trans-pubeschin. These are accompanied by ±-2,3-cis- and ±-2,3-trans-3-O-methylfustins, and by α, 2′,3,4,4′-pentahydroxychalcone. Other minor metabolises are 4′,7-dihydroxy- and 3′,4′,7-trihydroxy-flavanones and 5,6-dihydroxyphthalide. (+)-2,3-Trans-pubeschin trimethyl ether was synthesized by reduction of the corresponding (+)-2,3-trans-peltogynone analogue with NaBH₄/BF₃ in diglyme, and its absolute configuration shown to be 2R: 3S.     

Condensed tannins. Optically active diastereoisomers of (+)-mollisacacidin by epimerization

1. (+)-Mollisacacidin [(+)-3′,4′,7-trihydroxy-2,3-trans-flavan-3,4-trans- diol] is converted by autoclaving into the optically active free phenolic 2,3-trans-3-4-cis (12% yield), 2,3-cis-3,4-trans (11%) and 2,3-cis-3,4-cis (2·8%) diastereoisomers through epimerization at C-2 and C-4. 2. The relative configurations of the epimeric forms were determined by nuclear-magnetic-resonance spectrometry and paper ionophoresis in comparison with synthetic reference compounds, and was confirmed by chemical interconversions. 3. From this a scheme of epimerization is inferred and their absolute configurations are assigned as (2R:3S:4S), (2S:3S:4R) and (2S:3S:4S) respectively from the known absolute configuration (2R:3S:4R) of (+)-mollisacacidin.     

Biflavanoid proguibourtinidin carboxylic acids and their biflavanoid homologues from Acacia luederitzii

[4,6]- and [4,8]-Proguibourtinidin carboxylic acids (3,7,4′-trihydroxyl functionality) of 2,3-trans-3,4-trans: 2,3-cis- and 2,3-trans-3,4-trans: 2,3-trans-configuration based on (?)-epicatechin or (+)-catechin as constituent units, and their associated biflavanoid homologues, predominate in the heartwood of Acacia luederitzii. They are accompanied by stereochemical and functional analogues and by their putative flavan-3,4-diol and flavan-3-ol precursors.     

Chemical and enzymatic synthesis of monomeric procyanidins (leucocyanidins or 3′,4′,5,7-tetrahydroxyflavan-3,4-diols) from (2R,3R)-dihydroquercetin

The major product from the reduction of (2R,3R)-dihydroquercetin with sodium borohydride is the 2,3-trans-3,4-trans isomer of leucocyanidin [(2R,3S,4R-3,3′,4,4′,5,7-hexahydroxyflavan] whereas the enzymatic reduction product is the 2,3-trans-3,4-cis isomer [(2R,3S,4S)-3,3′,4,4′,5,7-hexahydroxyflavan]. The 3,4-trans isomer may be partly converted to the 3,4-cis isomer under mild acid conditions. The 3,4-cis isomer is more acid-labile, and more reactive both chemically with thiols and enzymatically with a diol reductase, than the 3,4-trans isomer.     

Natural and synthetic diastereoisomeric (?)-3′,4′,7-trihydroxyflavan-3,4-diols

1. Rhodesian copalwood (Guibourtia coleosperma) contains three diastereo-isomeric leuco-fisetinidins. These consist of the (−)-2,3-cis–3,4-cis (2R,3R,4R) and (−)-2,3-cis–3,4-trans (2R,3R,4S) 3′,4′,7-trihydroxyflavan-3,4-diols, and the third was shown to be a 2,3-trans–3,4-cis isomer by means of paper ionophoresis. 2. There occurrence in similar proportions as tannin precursors also in the tropical hardwoods G. tessmannii and G. demeusii implies a close taxonomic relationship between these, and with G. coleosperma. 3. Epimerization of the natural (−)-3′,4′,7- trihydroxy-2,3-trans-flavan-3,4-trans-diol affords a mixture from which the (−)-2,3-cis–3,4-cis isomer was separated readily, but the (−)-2,3-trans–3,4-cis isomer was obtained with difficulty. These were formed by epimerization of the (−)-2,3-trans–3,4-trans isomer at C-2 and C-4, and at C-4, respectively.     

The first 2,3-trans-3,4-cis procyanidin

Condensation of (+)-leucocyanidin with (+)-catechin under acidic conditions afforded the novel 2,3-trans-3,4-cis: 2,3-trans [4,8]-bi-[(+)-catechin] as the first representative of a 3,4-cis procyanidin unit.     

Prenylated flavonoids from seeds of Calopogonium mucunoides

The seeds of Calopogonium mucunoides furnished 7-O-γ,γ-dimethylallyl-8-methoxy-3′,4′-dioxymethylene-isoflavone, 7-O-γ,γ-dimethylallyl-3′-hydroxy-4′-methoxyisoflavone, 7-O-γ,γ-dimethylallyl-3′,4′-dimethoxyisoflavone and 2S-di[6′',6′'-dimethylpyrano (2′',3′':7,8;2′',3′':4′,3′)]-flavanone whose structures were established by spectroscopic means involving the use of 400 MHz ¹H NMR with double irradiation and INDOR techniques.     

Isolation and synthesis of trans- and cis-(−)-clovamides and their deoxy analogues from the bark of Dalbergia melanoxylon

N-(3′,4′-Dihydroxy-trans-cinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine [(?)-clovamide], the major phenolic metabolite (0.1%) in the bark of Dalbergia melanoxylon, is associated with minor proportions of its cis-isomer, and similar pairs of geometrical isomers of their deoxy analogues N-(4′-hydroxycinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine and N-(4′-hydroxycinnamoyl)-3-(4-hydroxyphenyl)-L-alanine. (?)-Trans-clovamide is synthesized by direct condensation of the acid chloride of caffeic acid with L-DOPA. Diagnostic CD spectra of these compounds and ¹³C spectra of (?)-trans- and (?)-cis-clovamides are recorded.     

Dimeric hydroanthracenes from the unripe seeds of Cassia torosa

From the unripe seeds of Cassia torosa three new dimeric hydroanthracene derivatives were isolated along with stigmasterol, sitosterol, campesterol, physcion-9-anthrone, torosachyrsone and the phlegmacins A₂ and B₂. The structures of the new derivatives were established as physcion-10, 10′-bianthrone, anhydrophlegmacin B₂ [2-(6′-methoxy-3′-methyl-3′, 8′, 9′-trihydroxy-1′-oxo-1′, 2′, 3′, 4′-tetrahydroanthracene-10′-yl)-1, 8-dihydroxy-3-methoxy-6-methyl-9-oxo-9, 10-dihydroanthracene] and torosanin [2-(6′-methoxy-3′-methyl-3′, 8′,9′-trihydroxy-1′-oxo-1′, 2′, 3′,4′-tetrahydroanthracene-5′-yl)-1, 8-dihydroxy-3-methoxy-6-methyl-9-oxo-9, 10-dihydroanthracene], respectively.     

Formation of (-⊃-1′,2′-epi-2-cis-xanthoxin acid from a precursor of abscisic acid

Tomato shoots and avocado mesocarp supplied with (±)-[2-¹⁴C]-5-(1,2-epoxy-2,6,6-trimethylcyclohexyl)-3-methylpenta-cis-2-trans-4-dienoic acid metabolize it into (+)-abscisic acid and a more polar material that was isolated and identified as (?)-epi-1′(R),2′(R)-4′(S)-2-cis-xanthoxin acid. The (+)-1′(S),2′(S)-4′(S)-2-cis-xanthoxin acid recently synthesized from natural violaxanthin, has the 1′,2′-epoxy group on the opposite side of the ring to that of the 4′(S)-hydroxyl group and the compound is rapidly converted into (+)-abscisic acid. The 1′,2′-epoxy group of (?)-1′,2′-epi-2-cis-xanthoxin acid is on the same side of the ring as the 4′(S) hydroxyl group: the compound is not metabolized into abscisic acid. The configuration of the 1′,2′-epoxy group probably controls whether or not the 4′(S) hydroxyl group can be oxidized. (+)-2-cis-Xanthoxin acid is probably not a naturally occurring intermediate because a ‘cold trap’, added to avocado fruit forming [¹⁴C]-labelled abscisic acid from [2-¹⁴C]mevalonate, failed to retain [¹⁴C] label.     

5-Methyl ether flavone glucosides from the leaves of Bruguiera gymnorrhiza

Two new 5-methyl ether flavone glucosides (7,4′,5′-trihydroxy-5,3′-dimethoxyflavone 7-O-β-D-glucopyranoside and 7,4′-dihydroxy-5-methoxyflavone 7-O-β-D-glucopyranoside) were isolated from the leaves of Thai mangrove Bruguiera gymnorrhiza together with 7,3′,4′,5′-tetrahydroxy-5-methoxyflavone, 7,4′,5′-trihydroxy-5,3′-dimethoxyflavone, luteolin 5-methyl ether 7-O-β-D-glucopyranoside, 7,4′-dihydroxy-5,3′-dimethoxyflavone 7-O-β-D-glucopyranoside, quercetin 3-O-β-D-glucopyranoside, rutin, kaempferol 3-O-rutinoside, myricetin 3-O-rutinoside and an aryl-tetralin lignan rhamnoside. The structure of a lignan rhamnoside was found to be related to racemiside, an isolated compound from Cotoneaster racemiflora, and also discussed. Structure determinations were based on analyses of physical and spectroscopic data including 1D- and 2D-NMR.     

Three highly oxygenated flavone glucuronides in leaves of Spinacia oleracea

Droplet counter-current chromatographic separation and subsequent TLC demonstrated the existence of at least 14 phenolics in the leaves of Spinacia oleracea. Three have now been isolated and identified, respectively, as the 4′-glucuronides of 5,7,4'-trihydroxy-3,6,3′-trimethoxyflavone (jaceidin), 5,3′,4′-trihydroxy-3-methoxy-6:7-methylene-dioxyflavone and 5,4′-dihydroxy-3,3′-dimethoxy-6:7-methylenedioxyflavone.     

Configuration of guibourtacacidin, and synthesis of isomeric racemates

1. Diacetates of the four possible racemates of 4′,7-dimethoxyflavan-3,4-diol have been synthesized. 2. Comparison of their nuclear-magnetic-resonance spectra and the ionophoretic mobilities of the diols in borate buffer with those of the corresponding derivatives of guibourtacacidin shows that the natural 4′,7-dihydroxyflavan-3,4-diol has a 2,3-cis–3,4-trans configuration, but is accompanied by 2,3-trans–3,4-trans and 2,3-trans–3,4-cis isomers. These occur in the approximate proportions 5:1:1. 3. The occurrence of guibourtacacidins in Guibourtia coleosperma appears to be of taxonomic significance. Their association with a large excess of related tannins in the heartwood suggests that flavan-3,4-diols with these configurations are suitable precursors in tannin biosynthesis.     

Studies on Abscisic Acid

Oxidation of methvl 2-trans-β-ionylideneacetate with X-bromosuccinimide afforded methyl 2-cis and trans-3′-hydroxy-β-ionylideneacetates. NaBH₄ reduction of methyl 2-cis-3′-keto-β-ionylideneacetate and ethyl 4′-keto-α-ionylideneacetate gave methyl 2-cis-3′-hydroxy-β-ionylideneacetate and ethyl 4′-hydroxy-α-ionyiideneacetate respectively. Further, methyl 4′-methoxy-epoxy-α-ionylideneacetate was prepared by epoxidation of methyl 4′-methoxy-α-ionylideneacetate. And then methyl 4′-hydroxy-l′, 2′-dihydro-β-ionylideneacetate was synthesized from ethyl 4-keto-α-cyclogeranate. Growth inhibitory activities of the above compounds on rich seedlings were examined.     

Benzofuranoid neolignans from Aniba simulans

Forteen neolignans, isolated from the benzene extract of Aniba simulans (Lauraceae) trunk wood, included the hitherto undescribed (2S, 3S, 5R)-5-allyl-5,7-dimethoxy-2-(3′,4′,5′-trimethoxyphenyl)-3-methyl-2,3,5,6-tetra-hydro-6-oxobenzofuran, (2R,3S,5R) -5-allyl-5-methoxy-2-(3′-methoxy-4′,5′-methylenedioxyphenyl)-3-methy1-2,3,5, 6-tetrahydro-6-oxobenzofuran, (2S,3S)-6-O-allyl -5-methoxy-2-(3′-methoxy-4′-5′-methylenedioxyphenyl)-3-methyl-2,3-dihydrobenzofuran, (2R,3S)-6-O-allyl-5-methoxy-2- (3′-methoxy-4′,5′-methylenedioxyphenyl)-3-methyl-2,3-dihydrobenzofuran and 7-allyl-6-hydroxy-5-methoxy-2-(3′-methoxy-4,5′ -methylenedioxyphenyl)-3-methylbenzofuran.     

Cyclisation of 1-trans-1′-norsqualene-2,3-epoxide and 1-cis-1′-norsqualene-2,3-epoxide by a cell free system of corn embryos

Squalene-2,3-epoxide-cycloartenol cyclase and cycloeucalenol-obtusifoliol isomerase activities were found in microsomal fractions of corn (Zea mays) embryos. Squalene-2,3-epoxide, 1-trans-1′-norsqualene-2,3-epoxide and 1-cis-1′-norsqualene-2,3-epoxide were incubated. Squalene-2,3-epoxide was cyclized giving only cycloartenol, whereas 1-trans-1′-norsqualene-2,3-epoxide gave 31-norcycloartenol and 31-norlanosterol with a reduced yield, 1-cis-1′-norsqualene-2,3-epoxide was not significantly cyclized.     

Flavonoids of the liverwort Marchantia polymorpha

The major flavonoids of Marchantia polymorpha var. polymorpha and aquatica are the 7-O-β-d-glucuronides of apigenin and luteolin, luteolin 3′-O-β-d-glucuronide, luteolin 7,3′-di-O-β-d-glucuronide, and the 7,4′-di-O-β-d-glucuronides of apigenin and luteolin. These are accompanied by minor amounts of apigenin, luteolin, luteolin 3′,4′-di-O-β-d-glucuronide and luteolin 7,3′,4′-tri-O-β-d-glucuronide. All the luteolin di- and triglucuronides except the 3′,4′-di- substituted compound are new natural products.     

Lignan glycosides from the Rhizomes of Smilax trinervula and their Biological activities

Phytochemical investigation of the rhizomes of Smilax trinervula led to isolation and structure elucidation of eight lignan glycosides, including five new lignans, namely, (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4′-O-β-d-glucopyranoside (1), (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4-O-β-d- glucopyranoside (2) (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-4′, 7-epoxy-8, 5′-neolignan 9′-O-β-d-glucopyranoside (3), (7R, 8R)-4, 9, 9′-trihydroxy-3, 5-dimethoxy-7.O.4′, 8.O.3′- neolignan 9′-O-β-d-glucopyranoside (4), and (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-8, 4′-oxy-neolignan 4-O-β-d-glucopyranoside (5), along with three known compounds (6-8). Their structures were established mainly on the basis of 1D and 2D NMR spectral data, ESI–MS and comparison with the literature. Compounds 1-8 were tested in vitro for their cytotoxic activity against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Compounds 3 and 5 exhibited cytotoxic activity against Lovo cells, with IC₅₀ value of 10.4 μM and 8.5 μM, respectively.