Isoflavan Derivatives Research Articles

Iridium-Catalyzed Asymmetric Hydrogenation of 2H-Chromenes: A Highly Enantioselective Approach to Isoflavan Derivatives.

A highly efficient (aS)-Ir/In-BiphPHOX-catalyzed asymmetric hydrogenation of substituted 2H-chromenes and substituted benzo[e][1,2]oxathiine 2,2-dioxides is described. A series of 2H-chromenes and benzo[e][1,2]oxathiine 2,2-dioxides were hydrogenated to give the target products in high yields (92-99%) with excellent enantioselectivities (up to 99.7% ee) using our catalytic system. This reaction provides a direct and efficient method for the construction of chiral benzo six-membered oxygen-containing compounds.

In Vitro Study of Isoflavones and Isoflavans as Potent Inhibitors of Human 12‐ and 15‐Lipoxygenases

In this study, we have investigated 16 isoflavone and isoflavan derivatives as potential inhibitors of human lipoxygenase (platelet 12-lipoxygenase, reticulocyte 15-lipoxygenase-1, and epithelial 15-lipoxygenase-2). The flavonoid baicalein, a known lipoxygenase inhibitor, was used as positive control. Four compounds, 6,7-dihydroxy-3'-chloroisoflavone (1c), 7-hydroxy-8-methyl-4'-chloroisoflavan (5a), 7,8-dihydroxy-4'-methylisoflavan (5b), and 7,8-dihydroxy-3'-methylisoflavan (5c), were effective inhibitors of 12-lipoxygenases and 15-lipoxygenase-1 with IC50 's <10μm, while 6,7-dihydroxy-4'-nitroisoflavone (1b) was a selective inhibitor of 12-lipoxygenases. Docking studies, antioxidant assays, and kinetic measurements were carried out for the three best inhibitors (1b, 5b, 5c). The results showed that a catechol group in ring A is critical for the antioxidant properties of these compounds, and probably essential for their inhibitory activity. Kinetic assays showed that compounds 1b, 5b, and 5c are competitive inhibitors with Ki values in the range of 0.3-3μm.

Mechanism of anti-inflammatory action of liquorice extract and glycyrrhizin

The antiradical activity, protective effect against lipid peroxidation of liposomal membrane, and inhibitory effect on whole blood reactive oxygen species (ROS) liberation of Glycyrrhiza glabra crude extract and glycyrrhizin, its major compound, were assessed. The liquorice extract showed significant activity in all the three assay systems used in a dose dependent manner. It displayed remarkable reactivity with free stable 1,1′-diphenyl-2-picrylhydrazyl (DPPH) radical, inhibitory efficacy in peroxidatively damaged unilamellar dioleoyl phosphatidylcholine (DOPC) liposomes, and inhibition of ROS chemiluminescence, generated by whole blood, induced by both receptor-bypassing stimuli (PMA) and receptor operating stimuli (Opz) in the ranking order of stimuli PMA> Opz. These activities may be attributed to phenolic antioxidants involving isoflavan derivatives, coumarins and chalcones. Nonetheless, triterpene saponin glycyrrhizin exhibited no efficacy in the system of DPPH reaction and peroxidation of liposomal membrane, and negligible inhibition of chemiluminescence generated by inflammatory cells. These results indicate that the mechanism of anti-inflammatory effect of glycyrrhizin most probably does not involve ROS and this major constituent is not responsible for the inhibition effects of liquorice extract on neutrophil functions.

Isolation and GC-MS determination of flavonoids from Glycyrrhiza glabra root

Components of the ethylacetate extract of Glycyrrhiza glabra root were separated based on their acid-base properties. The major components of the fraction soluble in aqueous NaOH were identified by GC-MS as glabridin, the principal component of the ethylacetate extract of licorice root (Glycyrrhiza glabra L.), 4-O-methylglabridin, and hispaglabridin B. The isoflavene glabrin was identified in addition to the isoflavan derivatives.

Structural Aspects of The Inhibitory Effect of Glabridin on LDL Oxidation

The inhibitory effects of glabridin, an isoflavan isolated from licorice ( Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced by copper ions or mediated by macrophages were studied, in order to evaluate the contribution of the different parts of the isoflavan molecule to its antioxidant activity. The peak potential (E 1/2 ) of the isoflavan derivatives, their radical scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and their ability to chelate heavy metals were also analyzed and compared to their inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation, glabridin (1), 4′- O-methylglabridin (2), hispaglabridin A (3), and hispaglabridin B (4), which have two hydroxyl groups at positions 2′ and 4′ or one hydroxyl at position 2′ on ring B, successfully inhibited the formation of conjugated dienes, thiobarbituric acid reactive substances (TBARS) and lipid peroxides, and inhibited the electrophoretic mobility of LDL under oxidation. Compounds 1–3 exhibited similar activities, whereas compound 4 was less active. In macrophage-mediated LDL oxidation, the TBARS formation was also inhibited by these isoflavans (1–4) at a similar order of activity to that obtained in copper ion-induced LDL oxidation. On the other hand, 2′- O-methylglabridin (5), a synthesized compound, whose hydroxyl at 2′-position is protected and the hydroxyl at 4′-position is free, showed only minor inhibitory activity in both LDL oxidation systems. 2′,4′- O-Dimethylglabridin (6), whose hydroxyls at 2′- and 4′-positions are both protected, was inactive. Resorcinol (7), which is identical to the phenolic B ring in glabridin, presented low activity in these oxidation systems. The isoflavene glabrene (8), which contains an additional double bond in the heterocyclic C ring, was the most active compound of the flavonoid derivatives tested in both oxidation systems. The peak potential of compounds 1–5 (300 μM), tested at pH 7.4, was similar (425–530 mV), and that for compound 6 and 8 was 1078 and 80 mV, respectively. Within 30 min of incubation, compounds 1, 2, 3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%, respectively, of DPPH radical, whereas compounds 5 and 6, which almost did not inhibit LDL oxidation, also failed to scavenge DPPH. None of the isoflavan derivatives nor the isoflavene compound were able to chelate iron, or copper ions. These results suggest that the antioxidant effect of glabridin on LDL oxidation appears to reside mainly in the 2′ hydroxyl, and that the hydrophobic moiety of the isoflavan is essential to obtain this effect. It was also shown that the position of the hydroxyl group at B ring significantly affected the inhibitory efficiency of the isoflavan derivatives on LDL oxidation, but did not influence their ability to donate an electron to DPPH or their peak potential values.

Five New Isoprenoid-substituted Flavonoids, Kanzonols M - P and R, from Two Glycyrrhiza Species

Three new formylated isoflavan derivatives, kanzonols M, N, and O, and a new prenylated pterocarpan derivative, kanzonol P, were isolated from Glycyrrhiza uralensis along with kanzonol Q (dihydroxanthoxyletin). A new prenylated isoflavan derivative, kanzonol R, was isolated from G. glabra. These structures were elucidated on the basis of spectrometric evidence

Five New Isoprenoid-substitued Flavonoids, Kanzonols F - J, from Glycyrrhiza uralensis

A new isoprenoid-substituted pterocarpan derivative, kanzonol F, a new isoflavanone derivative, kanzonol G, and three new isoflavan derivatives, kanzonols H, I, J, were isolated from Glycyrrhiza uralensis. These structures were elucidated with spectroscopic and/or chemical methods

Enantiomeric separation of racemic isoflavanones and related compounds on (+)-poly(triphenylmethyl methacrylate)-coated silica gel

(+)-Poly(triphenylmethyl methacrylate)-coated silica gel [Chiralpack OT(+)] was used for the separation of enantiomers of racemic isoflavanone, homoisoflavanone, isoflavan and 2-benzyltetralone derivatives. All the enantiomers of the above-mentioned compounds were separable. The efficiency of the separation depended on both the skeleton and substitution pattern of the racemic compounds. A relation between the number and polarity of substituents in the aromatic rings and the resolution and separation factors was observed.

New hydroxyisoflavans as contact sensitizers in cocus wood Brya ebenus DC (Fabaceae)

A 15-year-old girl developed perioral dermatitis and swelling of the lips, having played a flute made of cocus wood for 2 years. Patch tests with wood shavings, as well as with subsequently isolated constituents named Cocus I and Cocus II, were strongly positive. After complete purification, both contact allergens were identified as isoflavan derivatives. While Cocus I was shown to be 7,8-dihydroxy-2',4',5'-trimethoxyisoflavan, the structure of Cocus II could not be elucidated exactly. It could have been either 7,8,3'-trihydroxy-2',4'-dimethoxyisoflavan or 7,8,2'-trihydroxy-3',4'-dimethoxyflavan. The exact position of the hydroxy and methoxy group in C-2' and C-3' can be determined only by complete synthesis of both compounds or by isolation of greater amounts of Cocus II for further oxidation experiments. Due to the stronger patch test reaction and the higher yield of Cocus I in the wood, this hydroxyisoflavan must be recognized as the main contact allergen.

Expression of pisatin demethylating ability in Nectria haematococca

A mycelial suspension of Nectria haematococca completely demethylated 0.1 mM pisatin in 2 h in a medium free of other carbon sources while no demethylation of pisatin by the fungus occurred in 6 h when 2% glucose was in the medium. Prior exposure of the fungal cells to pisatin in glucosefree medium markedly enhanced the rate of pisatin demethylation, with maximum stimulation occurring 5–9h after the initial exposure. The stimulation of pisatin demethylating ability was relatively specific for pisatin as the inducer. Out of a large variety of isoflavonoids tested the only compounds other than pisatin that stimulated the activity significantly were pterocarpan or isoflavan derivatives. Protoplasts with pisatin demethylating ability were isolated from pisatin-treated mycelium. Attempts to obtain a cell-free system with pisatin demethylating ability from these protoplasts were unsuccessful.

Phytoalexin induction and its chemosystematic significance in the genus Trigonella

Using the drop-diffusate technique, a number of isoflavonoid phytoalexins have been obtained from the excised, fungus-inoculated leaflets of 41 species belonging to the legume genus Trigonella. Leaf diffusates variously contained pterocarpan (medicarpin and maackiain) and isoflavan (vestitol and sativan) derivatives previously associated with genera closely allied to Trigonella. In diffusates from T. calliceras, medicarpin was accompanied by a phytoalexin (designated TC-1) provisionally identified as a new hydroxylated pterocarpan. Most of the Trigonella species were also examined for their ability to release coumarin upon tissue maceration. The combined phytoalexin/coumarin data suggest that three major intrageneric chemical divisions occur in Trigonella; two of these apparently link the genus to Medicado/Factorovskya and Melilotus respectively, whilst the third provides some evidence for a connection with Trifolium. The taxonomic aspects of these findings are discussed in the light of earlier morphological studies which provided evidence for a distinct floral dichotomy amongst Trigonella species.

The Absolute and Relative Stereochemical Correlation of Isoflavanone, Sophorol and Naturally-occurring Isoflavan Derivatives

Abstract By rotatory-dispersion studies, it was confirmed that sophorol, (−) maackiain, pterocarpin, equol and homopterocarpin have the same absolute configuration at position 3. The results of the O. R. D. examination of (−) halostachine and pterocarpinoids allow us to assign the 3R, 4R configuration to pterocarpin and to the related compounds.

The Absolute and Relative Stereochemical Correlation of Isoflavanone, Sophorol and Naturally-occurring Isoflavan Derivatives

The Absolute and Relative Stereochemical Correlation of Isoflavanone, Sophorol and Naturally-occurring Isoflavan Derivatives