Total synthesis of the pyranoisoflavone kraussianone 1 and related isoflavones.

The first total synthesis of the pyranoisoflavone kraussianone 1 (1) is described. The key steps involved the Suzuki-Miyaura reaction for the construction of the isoflavone core and the regioselective formation of the dimethylpyran scaffolds to the phloroglucinol (ring A) and resorcinol (ring B) moieties of kraussianone 1 (1). This route also provided access to the related isoflavones eriosemaone D (2) and genistein (3) via simple structural modifications.

The chemical structures, plant origins, ethnobotany and biological activities of homoisoflavanones.

This work reviews the four basic structural types of homoisoflavanones. The relationships between the various structures of homoisoflavanones and their plant origins, ethnobotany and biological activities are put into perspective.

Antimicrobial acylphloroglucinols and dibenzyloxy flavonoids from flowers of Helichrysum gymnocomum.

From the dichloromethane extract of the flowers of Helichrysum gymnocomum (Asteraceae) two known flavonoids, 4 and 5, and a known acylphloroglucinol, 3B, were isolated. In addition to 1 and 2, the 4',6'-dibenzyloxy-2'-hydroxy derivative of 2',4',6'-trihydroxychalcone and 5,7-dibenzyloxy derivative of pinocembrin, respectively, are reported in Nature for the first time. A compound 3A, related to 3B has the structure 2-methyl-1-[2,4,6-trihydroxy-3-(2-hydroxy-3-methyl-3-butenyl)phenyl]-1-propanone. Compounds 1, 2, 3A, 3B, 4 and 5 have MIC values below 64microg/ml against a selection of pathogens, with 3B having the highest sensitivity (6.3-45microg/ml) for eight of the ten pathogens tested, including Staphylococcus aureus (6.3microg/ml) and methicillin and gentamycin resistant strain of S. aureus (7.8microg/ml). With the exception of 2, the other compounds had notable activity (45-63microg/ml) towards Pseudomonas aeruginosa.

Bufadienolides from bulbs of Urginea lydenburgensis (Hyacinthaceae: Urgineoideae).

Bulbs of the ethnomedicinal hyacinthac Urginea lydenburgensis have yielded two bufadienolides, 16beta-acetoxy-3beta,14beta-dihydroxy-19-formyl-bufa-4,20,22-trienolide (scillicyanosidin) and 4beta,8beta,11alpha,14beta-tetrahydroxybufa-5,20,22-trienolide-12-one, 2alpha,3beta-O-4,6-dideoxy-L-glucose (lydenburgenin).

Antimicrobial monomeric and dimeric diterpenes from the leaves of Helichrysum tenax var tenax.

The hexane extract of fresh air-dried leaves of Helichrysum tenax (Asteraceae) afforded ent-beyer-15-en-19-ol (1), its 4-epimer ent-beyer-15-en-18-ol (2), 15beta,16beta-epoxide-ent-beyeran-19-ol (3), as well as (4) consisting of two units of (1) linked as a diester of malonic acid, and (5), a compound. Its constituents are (1) and (3) also linked as a diester of malonic acid. The leaves of the plant are densely covered in fine glandular trichomes. These are extremely sticky and exude a mixture of the above diterpenes. Antimicrobial tests showed that (1), in particular, was highly active (3.1 and 3.6 microg/ml) against Bacillus cereus and Staphylococcus epidermidis, respectively.

Vasodilatory and hypoglycaemic effects of two pyrano-isoflavone extractives from Eriosema kraussianum N. E. Br. [Fabaceae] rootstock in experimental rat models.

Zulu traditional health practitioners have claimed that the roots of Eriosema kraussianum N. E. Br. (Fabaceae) and other Eriosema species (Zulu indigenous umbrella name of "uBangalala") are effective remedies for the treatment of erectile dysfunction (ED) and/or impotence. In order to scientifically appraise the significance and contribution of Eriosema kraussianum to its ethnomedical use as "uBangalala" and "VIAGRA substitute", the present study was undertaken to investigate the vasodilatory and hypoglycaemic properties of the two main bioactive chemical compounds obtained from E. kraussianum, in experimental rat models, using sildenafil citrate (VIAGRA) as the reference drug for comparison. The two E. kraussianum rootstock constituents (K1 and K2, 20-80 mg/kg p.o.) caused dose-dependent and significant (P<0.05-0.001) hypoglycaemia in rats. Relatively low to high concentrations of the plant's extracts (K1 and K2, 100-2000 microg/ml) always produced biphasic effects on rat isolated portal veins. K1- and K2-provoked responses of the isolated portal veins always consisted of concentration-related initial transient, but significant (P<0.05), contractions of the venous muscle preparations, followed by secondary, longer-lasting, highly significant (P<0.01-0.001) relaxations of the venous muscle strips. Sildenafil citrate (VIAGRA, 5-100 microg/ml) always produced concentration-related and highly significant relaxations of the rat isolated portal veins. Unlike K1 and K2 (20-80 mg/kg p.o.), however, sildenafil citrate (VIAGRA, 100 mg/kg p. o.) only caused slight and insignificant (P>0.05) reductions in the blood glucose levels of the experimental animals used. On the other hand, glibenclamide (10 mg/kg p.o.) induced highly significant (P<0.05-0.001), marked reductions in the blood glucose concentrations of the rats. The findings of this laboratory animal study indicate that the two hydro-ethanol extractives of E. kraussianum (K1 and K2) possess hypoglycaemic and secondary, vasorelaxant effects in the experimental paradigms used.

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).

Anti-inflammatory activity and QSAR studies of compounds isolated from Hyacinthaceae species and Tachiadenus longiflorus Griseb. (Gentianaceae).

Twenty-two homoisoflavanones and structurally related compounds isolated from plants were screened for anti-inflammatory activity. Seventeen compounds were isolated from southern African Hyacinthaceae species, one from the Madagascan gentian Tachiadenus longiflorus Griseb. and four were of synthetic origin. Inhibition of prostaglandin synthesis in cell microsomal fractions was first evaluated, followed by screening for specific inhibition of isolated cyclooxygenase enzymes (COX-1 and COX-2). Six homoisoflavanone and structurally related compounds showed significantly high levels of anti-inflammatory activity in the microsomal fraction assay. Only one compound exhibited a high level of anti-inflammatory activity in the COX-1 enzyme assay and no significant activity was detected in the COX-2 enzyme assay. Biological screening was followed by a computer-based quantitative structure-activity relationship (QSAR) study. The physicochemical descriptors: strain energy, heat of formation, volume, surface area, aqueous phase energy, dipole moment, enthalpy, entropy, molar refractivity, parachor, density, refractive index, surface tension, polarizability, logP, Van der Waals interaction energy, Coulombic interaction energy and nonbonded interaction energy were used to characterize the structures of the homoisoflavanones and structurally related compounds. This study produced three equations with significant prediction values for the anti-inflammatory activity of the compounds investigated. The derived models also provided valuable parameter guidelines for those properties influencing the anti-inflammatory activity of the studied compounds.

Minor pyrano-isoflavones from Eriosema kraussianum: activity-, structure-, and chemical reaction studies.

The isolation and identification of two minor pyrano-isoflavones from Eriosema kraussianum is described. New studies on the original pyrano-isoflavones shows that: (i) kraussianone 2 (a major compound in the plant) can be cyclised under acid conditions, (ii) kraussianones 3 and 5 cause contraction (not relaxation as anticipated) of corpus cavernosum tissue and (iii) the structures proposed previously for 4 and 5 are confirmed by the data obtained from an X-ray study of 5.

Venusol from Gunnera perpensa: structural and activity studies.

From the aqueous extract of the dry rhizomes of Gunnera perpensa the minor components pyrogallol, succinic acid, lactic acid, and the trimethyl ether of ellagic acid glucoside were isolated. The major constituent was identified as Z-venusol, a phenylpropanoid glucoside. Its structure was verified by X-ray diffraction. Tests on isolated uterine smooth muscle from rats showed that the whole extract stimulated a direct contractile response and induced a state of continuous contractility of the uterus once all additives had been removed from the organ bath. By contrast, venusol did not trigger the direct contractile response but induced the state of continuous contractility once the organ bath was flushed.

Recent findings on natural products with erectile-dysfunction activity.

Viagra has had a profound influence on the search for natural products with erectile-dysfunction activity. To date the "natural" equivalent is not in existence but several pure compounds from nature, e.g., Yohimbine, Citrulline, two pyrano-isoflavones, berberine, forskolin and others, have either been re-examined or are new potential candidates. Intense activity exists in the area of testing semi-purified plant extracts for erectile dysfunction activity.

Organ-to-organ and seasonal variation in alkaloids from Crinum macowanii.

The distribution and seasonal variation of alkaloids from Crinum macowanii were investigated. The alkaloids lycorine, 1-O-acetyllycorine, crinine, powelline, crinamine, crinamidine, 3-O-acetylhamayne, 1-epideacetylbowdensine and cherylline were isolated from this plant using gas chromatography. Significant organ-to-organ variations were detected for the alkaloids crinine, lycorine, powelline, crinamidine, 3-O-acetylhamayne and crinamine. Crinine, crinamidine and 1-epideacetylbowdensine showed significant seasonal variation.

Pyrano-isoflavones with erectile-dysfunction activity from Eriosema kraussianum.

Five pyrano-isoflavones have been isolated from the rootstock of Eriosema kraussianum N. E. Br (Papilionaceae). Spectral data and single crystal X-ray analyses were used for structural elucidation. The most active of the compounds had an activity of 75% of that found in Viagra in the erectile dysfunction test on rabbit penile smooth muscle.

Absolute configurations of all four stereoisomers of cryptocaryalactone and deacetyl cryptocaryalactone.

Using information available in the literature and correlating this with physical data obtained for cryptocaryalactone stereoisomers isolated from C. myrtifolia and C. wyliei, it has been possible to assign the absolute configurations of the four stereoisomers of the title compound and its deacetyl analogue.