Diarylpropanes from Iryanthera coriacea

The trunk wood of Iryanthera coriacea Ducke (Myristicaceae) contains six compounds which belong to the recently discovered 1,3-diarylpropane type of flavonoids, 1-(2-hydroxy-4-methoxyphenyl)-3-(3,4-methylenedioxyphenyl)-propane, 1-(2,4-dihydroxyphenyl)-3-(3,4-methylenedioxyphenyl)-propane, 1-(4-methoxyphenyl)-3-(2-hydroxy-4,5-methylenedioxyphenyl)-propane, 1-(4-hydroxy-2-methoxy-phenyl)-3-(4-hydroxy-3-methoxyphenyl)-propane, 1-(2,4-dihydroxyphenyl)-3-(2-methoxy-4,5-methylene-dioxyphenyl)-propane, 1-(2,4-dihydroxy-3,5-methylphenyl)-3-(2-hydroxy-4,5-methylenedioxyphenyl)-propane.     

Constitutions of diarylpropanoids from Virola multinervia

The wood of Virola multinervia Ducke (Myristicaceae) contains sitosterol, stigmasterol and two novel diarylpropanoids virolane [1-(2-hydroxy-4-methoxyphenyl)-3-(3,4-methylenedioxyphenyl)-propane] and virolanol [2-hydroxy-1-(2-hydroxy-4-methoxyphenyl)-3-(3,4-methylenedioxyphenyl)-propane].     

Antifungal Activity of Tetra-Substituted Tetrahydrofuran Lignan, (−)-Virgatusin,and Its Structure-Activity Relationship

Antifungal activities of the optically pure (>99%ee) (?)- and (+)-virgatusin, a tetra-substituted tetrahydrofuran lignan, were tested. (?)-Virgatusin, which is a natural product, showed highest antifungal activity against Colletotrichum lagenarium. Research on its structure-activity relationship was also performed. It was shown that two methoxy groups on 9 and 9′ positions and a 3,4-methylenedioxyphenyl group on the 7 position of virgatusin were essential for high fungal growth inhibition. The part on 7′-phenyl group was not essential for activity. The 7′-(4-methoxyphenyl) derivative showed higher activity than that of (?)-virgatusin.     

Studies on the Syntheses of the Pyrethrin Analogues and their Biological Activities

Some new allethronyl esters of cyclopropanecarboxylic acids were prepared, and their insecticidal activities were tested against common housefly. Allethronyl esters of cyclopropanecarboxylic acids having 3,4-methylenedioxyphenyl group on the cyclopropane ring were more or less toxic. Among them, allethronyl 2,2-dimethyl-3-(3′,4′-methylenedioxyphenyl)-cycloopropane-l-carboxylate was found to be more toxic than α-dl-trans-allethrin, and the calculated relative effectiveness were 1.48 and 1.21 on the mortality and knock-down activity respectively as compared with α-dl-trans-allethrin.     

Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (curcumin longa). It has been shown to exhibit a variety of biological activities including antioxidative activity. In order to find more active antioxidants with 1 as the lead compound we synthesized curcumin analogues, i.e., 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (3), 1,7-bis-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1-(3,4-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (5), 1,7-bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-dione (6), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (7), and evaluated their antioxidative activity. The in vitro oxidative damage to both lipids and proteins in rat liver mitochondria was used as a model to study the free radical-induced oxidative damage of biological lipids as well as proteins and the protective effects of these curcumin analogues. It was found that these compounds, except 6 and 7, could effectively inhibit the free radical induced lipid peroxidation and protein oxidative damage of rat liver mitochondria by H-atom abstraction from the phenolic groups. Compound 2 which bear ortho-diphenoxyl functionality exhibited remarkably higher antioxidative activity for lipids and proteins than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also play an important role in the antioxidative activity.     

Antifungal activity of tetra-substituted tetrahydrofuran lignan, (-)-virgatusin, and its structure-activity relationship

Antifungal activities of the optically pure (>99%ee) (-)- and (+)-virgatusin, a tetra-substituted tetrahydrofuran lignan, were tested. (-)-Virgatusin, which is a natural product, showed highest antifungal activity against Colletotrichum lagenarium. Research on its structure-activity relationship was also performed. It was shown that two methoxy groups on 9 and 9' positions and a 3,4-methylenedioxyphenyl group on the 7 position of virgatusin were essential for high fungal growth inhibition. The part on 7'-phenyl group was not essential for activity. The 7'-(4-methoxyphenyl) derivative showed higher activity than that of (-)-virgatusin.     

Influence on Insecticidal Activity of the 3-(3,4-Methylenedioxyphenyl) Group in the 1,4-Benzodioxanyl Moiety of Haedoxan

The influence on the insecticidal activity of haedoxan A of its 3-(3,4-methylenedioxyphenyl) group in the 1,4-benzodioxanyl moiety was examined with two (±)-(1S*,2R*,5R*,6S*)-6-[(2R*,3R*)-3-alkyl-6- methoxy-2-methoxymethyl-1,4-benzodioxan-7-yl]-2-(2,6-dimethoxyphenoxy)-1-hydroxy-3,7-dioxabicyclo-[3.3.0]octanes. Replacement of the methylenedioxyphenyl group of haedoxan by methyl and n-butyl group resulted in a large decrease in the activity, indicating the importance of the 3-aryl group for the potent insecticidal activity of haedoxan.     

Effect on Insecticidal Activity of Substituents at the 1,4-Benzodioxanyl Moiety of Haedoxan

The haedoxan analog, (±)-2-(2,6-dimethoxyphenoxy)-1-hydroxy-6-(6-methoxy-l,4-benzodioxan-7-yl)-3,7-dioxabicyclo[3.3.0]octane, and its congeners with 2-alkoxymethyl, 2-hydroxymethyl, 2-chloromethyl and 3-(3,4-methylenedioxyphenyl) substituents on the 1,4-benzodioxanyl group were synthesized from 6-methoxy-l,4-benzodioxan-7-carbaldehyde and its (±)-2- and 3-substituted derivatives, respectively. Some analogs were considerably insecticidal, although much less active than natural haedoxan A. The assay results suggest that 2,3-disubstitution on the 1,4-benzodioxanyl group was necessary to intensify the insecticidal activity.     

Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation: H-atom abstraction from the phenolic groups and possible involvement of the 4-hydroxy-3-methoxyphenyl groups

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (Curcumin longa). It has been shown to exhibit a variety of biological activities including antioxidative activity. In order to find more active antioxidants with 1 as the lead compound we synthesized curcumin analogues, i.e., 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1,7-bis (4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (5), 1-(3,4-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (6), 1,7-bis(3,4-dimethoxyphenyl)-1,6- heptadiene-3,5-dione (7), 1,7-bis(4-methoxyphenyl)-1,6-heptadiene-3,5-dione (8), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (9). Antioxidative effects of curcumin and its analogues against free radical initiated peroxidation of human low density lipoprotein (LDL) were studied. The peroxidation was initiated either by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), or by cupric ion (Cu2+). The reaction kinetics were monitored either by the uptake of oxygen and the depletion of alpha-tocopherol present in the native LDL, or by the formation of thiobarbituric acid reactive substances. Kinetic analysis of the antioxidation process demonstrates that these compounds, except 7, 8, and 9, are effective antioxidants against AAPH- and Cu2+ -initiated LDL peroxidation by H-atom abstraction from the phenolic groups. Compounds 2 and 3 which bear ortho-diphenoxyl functionality possess significantly higher antioxidant activity than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also play an important role in the antioxidative activity.     

Diarylheptanoids from the rhizomes of Zingiber officinale

Seven new diarylheptanoids, i.e., (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3-acetoxy-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxy-5-methoxy-phenyl)heptan-3-one and 1,5-epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane were isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe), along with 25 known compounds, i.e., 8 diarylheptanoids, 14 gingerol analogs, a diterpene and 2 steroids. Their structures were elucidated by spectroscopic and chemical methods.     

Synthesis and Insecticidal Activity of Lignan Analogs (II)

The influence of the 6-methoxy-2-methoxymethyl-3-(3,4-methylenedioxyphenyl)-1,4-benzodioxan-7-yl group on the insecticidal activity of haedoxans was studied by synthesizing an analog without the (methoxymethyl)methinoxy moiety of the benzodioxanyl group to test for its activity on the housefly. The inactivity of the analog and its satellite compounds implies that the (methoxymethyl)methinoxy moiety is essential for the biological activity of haedoxans.     

The structure of macelignan from Myristica fragrans

A new lignan, macelignan, isolated from the arils of Myristica fragrans, is shown to have the structure (2R,3S)-1-(3,4-methylenedioxyphenyl)-2,3-dimethyl-4-(4-hydroxy-3-methoxyphenyl)-butane by spectral analysis, chemical conversion and X-ray crystallographic analysis.     

Inhibition of Sporulation of Genus Bacillus by Various Microbial Protease Inhibitors

Several analogs modifying the 6-methoxy-2-methoxymethyl-3-(3,4-methyienedioxyphenyl)-1,4-benzodioxan-7-yl group of haedoxans were synthesized and their insecticidal activity was examined. 2-(2,6-Dimethoxyphenoxy)-1-hydroxy-6-(2-methoxy-5-methoxyethoxyphenyl)-3,7-dioxabicyclo-[3.3.0]octane, which lacked the 3-(3,4-methylenedioxybenzyloxy) moiety of the benzodioxanyl group, was not insecticidal, but caused prolonged paralysis of the housefly. A compound replacing the 6-(2-methoxy-5-methoxyethoxyphenyl) by 6-(5-butoxy-2-methoxyphenyl) exhibited insecticidal activity comparable to one thirty-thousandth of that of haedosan A. It became evident that the 1,4-benzodioxane framework charging the 3-(3,4-methylenedioxy)phenyl group is important for the insecticidal activity of haedoxans.     

Horsfieldin,a lignan and other constituents from Horsfieldia iryaghedhi

A new lignan, horsfieldin [2-(3-hydroxy-4-methoxyphenyl)-6-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo(3,3,0)octane], d-asarinin, (?)-dihydrocubebin, dodecanoylphloroglucinol, myristic acid, trimyristin and sitosterol have been isolated and characterized from the hot methanol extract of Horsfieldia iryaghedhi seeds. The absolute configuration of the lignans and the chemotaxonomic significance of their occurrence is discussed.     

Effect of 4-Thiouridine on Chloroplast Development

The methoxymethyl group of the 6-methoxy-2-methoxymethyl-3-(3,4-methylenedioxyphenyl)-1,4-benzodioxan-7-yl moiety of insecticidallignans of Phryma was modified with sereral alkyl groups to evaluate the effect on activity of the substituents. The assay results make it evident that this activity was significantly modified by the chain length or bulkiness of the alkyl groups and that the oxygen atom of the methoxymethyl group was fairly important for enhancing the activity.     

Diarylpropanes from the wood of Iryanthera grandis

Trunk wood of Iryanthera grandis contains 1(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-(3″,4″-methylenedioxyphenyl)-propane and 1(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-(3″-methoxy-4″-hydroxyphenyl)-propane, as well as three additional known diarylpropanes, a new flavan (±)-5,7-dimethoxy-4′-hydroxyflavan and the known (±)-7,4′-dihydroxy-3′-methoxyflavan.     

Oxidation and reduction of lignin-related aromatic compounds by Aureobasidium pullulans

Summary A yeast-like fungus, identified as Aureobasidium pullulans, was isolated from a kraft mill settling pond by enrichment culture on 1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-propane-1,3-diol (I). The fungus was also able to use the following aromatic acids as sole carbon source: Benzoic, p-hydroxybenzoic, vanillic, syringic, ferulic and protocatechuic acids. Various aromatic alcohols were oxidised to their corresponding aldehydes and acids during aerobic culture, while aromatic aldehydes were both oxidised and reduced. However, the aromatic acids were not reduced, but were slowly metabolised. Dimer I was cleaved at the alkyl-phenyl linkage to give glycerol-2-guaiacyl ether in high yield. The identity of the latter was determined by mass spectrometry and proton nmr. The dimers 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)-propane-1,3-diol (II), 3,4-dimethoxy--(2,6-dimethoxy-4-carboxyphenoxy)-acetophenone (III) and 5-carboxy-7-methoxy-2-(4-hydroxy-3-methoxyphenyl)-3-methyl-2,3-dihydrobenzo-[b]-furan (IV) were not metabolised. It is concluded that the fungus resembles Fusarium in many of its metabolic properties, and could be considered as a potential lignin degrader.     

Effect of the structure of dietary epoxylignan on its cytotoxic activity: relationship between the structure and the activity of 7,7′-epoxylignan and the introduction of apoptosis by caspase 3/7

We compared the cytotoxic activities of dietary epoxylignans and their stereoisomers and found (?)-verrucosin, which is (7S,7′R,8R,8′R)-7,7′-epoxylignan, to be the most cytotoxic epoxylignan against HeLa cells (IC₅₀ = 6.6 μM). On the other hand, the activity was about a factor of 10 less against HL-60. In this research on the relationship between the structure and cytotoxic activity of (?)-verrucosin 13, the 7-(4-methoxyphenyl)-7′-(3,4-dimethoxyphenyl) derivative 60, for which the activity (IC₅₀ = 2.4 μM) is three times greater than (?)-verrucosin 13, was discovered. The induction of apoptosis by caspase 3/7 was observed upon treatment with the (?)-verrucosin derivative.     

Synthesis of the Thiirane Analogs of Juvenile Hormone III and Other Juvenile Hormone Mimics

Methyl (2E,6E)-10,11-epithio-3,7,11-trimethyl-2,6-dodecadienoate (the thiirane analog of JH III), 6,7-epithiogeranyl 4-methylphenyl ether and 6,7-epithiogeranyl 3,4-methylenedioxyphenyl ether were synthesized. An infrared absorption band at ~1090 cm^?1 was attributable to the thiirane group. The biological activity of these three sulfur-containing JH mimics was tested on Culex pipiens, Aedes aegypti and Spodoptera litura to reveal weak or no JH-like activity.     

6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives: a novel class of endothelin receptor antagonists

Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC(50) value of 2.4 nM against (125)I-labeled ET-1 binding to human ET(A) receptors and a 170-fold selectivity for ET(A) over ET(B) receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound 1 in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization on substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ET(A) selective antagonist 2p with an IC(50) value of 0.87 nM for ET(A) receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model.