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.     

Comparison of pH-sensitive degradability of maleic acid amide derivatives

We synthesized five maleic acid amide derivatives (maleic, citraconic, cis-aconitic, 2-(2′-carboxyethyl) maleic, 1-methyl-2-(2′-carboxyethyl) maleic acid amide), and compared their degradability for the future development of pH-sensitive biomaterials with tailored kinetics of the release of drugs, the change of charge density, and the degradation of scaffolds. The degradation kinetics was highly dependent upon the substituents on the cis-double bond. Among the maleic acid amide derivatives, 2-(2′-carboxyethyl) maleic acid amide with one carboxyethyl and one hydrogen substituent showed appropriate degradability at weakly acidic pH, and the additional carboxyl group can be used as a pH-sensitive linker.     

A new bicyclic sesquiterpene from the marine sponge associated fungus Emericellopsis minima

A new sesquiterpene (5E)-2-methyl-5-[(1′R*, 5′R*)-2-methylidene-7-oxobicyclo[3.2.1]oct-6-ylidene]-4-oxopentanoic acid (1) was isolated, in addition to the dihydroisocoumarin cis-(3R, 4R)-4-hydroxymellein, ergosterol peroxide and helvolic acid, from the culture of the fungus Emericellopsis minima associated with the marine sponge Hyrtios erecta. The structures of all the compounds were elucidated using spectroscopic data from 1D, 2D NMR and HRESITOFMS. Compounds 1 and cis-(3R, 4R)-4-hydroxymellein were found to show neither antimicrobial nor the in vitro growth inhibitory activities on three human tumor cell lines.     

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.     

Partial purification and characterization of the linoleate hydroperoxide isomerase from grains of Hordeum distichum

Linoleate hydroperoxide isomerase was mainly located in the embryos of barley grains and its activity decreased during germination. The enzyme partially purified from embryos converted 9-hydroperoxy, trans-10, cis-12-octadecadienoic acid to 9-hydroxy, 10-oxo, cis-12-octadecenoic acid and 13-hydroxy, 10-oxo, trans-11-octadecenoic acid in the ratio of ca 2:1.     

Reaction of Astaxanthin with Peroxynitrite

The in vitro reactivities of astaxanthin toward peroxynitrite were investigated and the reaction products after scavenging with peroxynitrite were analyzed in order to determine the complete mechanism of this reaction. A series of carotenoids, 13-apo-astaxanthinone (1), 12′-apo-15′-nitroastaxanthinal (2), 12′-apo-astaxanthinal (3), 10′-apo-astaxanthinal (4), 9-cis-14′-s-cis-15′-nitroastaxanthin (5), 14′-s-cis-15′-nitroastaxanthin (6), 13-cis-14′-s-cis-15′-nitroastaxanthin (7), 10′-s-cis-11′-cis-11′-nitroastaxanthin (8), 13,15,13′-tri-cis-15′-nitroastaxanthin (9), 9-cis-astaxanthin (10), and 13-cis-astaxanthin (11), were isolated from the reaction products of carotenoids with peroxynitrite. Our previous studies achieved for the first time the isolation of nitro derivatives from the reaction of astaxanthin with peroxynitrite. Here we identify the major remaining reaction products of this reaction and investigate the stabilities of the nitro astaxanthins.     

Agents related to a potent activator of the acetylcholine receptor of Electrophorus electricus

The synthesis of a number of compounds related to trans-3,3′-bis[α-(trimethylammonium)methyl]azobenzene dibromide (trans-3,3′-BisQ) (1)1 is described. Among the compounds are: [¹⁴C]-trans-3,3′-BisQ (1)1 diiodide, cis-3,3′-BisQ (2)1 dibromide, the trans-2,2′ (7)1 and 4,4′ (11)1 isomers of BisQ, 2,2′, (12)1, 3,3′ (13)1 and 4,4′ (14)1 isomers of bis-benzyldimethylammonium analogues, and related compounds in which the azo bridge between the two aromatic rings is replaced by diketo and amide bridges. Of them all, trans-3,3′-BisQ (1)1 was the most active cholinergic compound in the electroplax system of Electrophorus electricus; the pure cis isomer (2)1 was without activity. Intermediate activities were found for some of the other compounds and others were inhibitors. The relationship of the structure of these agents to a proposed conformation and topography of the binding site of the acetylcholine receptor (AChR) is discussed.     

Occurrence of some mono-cis-isomers of asymmetric C40-carotenoids

The 9-cis-isomers of antheraxanthin [(3S,5R,6S)-5,6-epoxy-5,6- dihydro-β, β-carotene-3,3′-diol] and lutein epoxide [(3S,5R,6S, 3′R,6′R)-5,6-epoxy-5,6-dihydro-β, ε-carotene-3,3′-diol] were found to occur without their 9′-cis counterparts in the non-photosynthetic tissues of several higher plants. 9-cis-lutein [(3R,3′R,6′R)- β,ε-carotene-3,3′-diol], on the other hand, was observed together with its 9′-cis counterpart in the samples investigated. The qualitative distribution of carotenoids is also reported.     

Combined effects of oleic,linoleic and linolenic acids on lactation performance and the milk fatty acid profile in lactating dairy cows

The potential combined effects of oleic, linoleic and linolenic acids supplementation on lactation performance and the milk fatty acid (FA) profile in dairy cows have not been well investigated. Our objective was to examine the effects of supplementation with a combination of these FA as well as the effects of removing each from the combination on lactation performance and the milk FA profile in dairy cows. Eight Holstein cows (101±11 days in milk) received four intravenously infused treatments in a 4×4 Latin square design, and each period lasted for 12 days which consisted of 5 days of infusion and 7 days of recovery. The control treatment (CTL) contained 58.30, 58.17 and 39.96 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively. The other three treatments were designated −−C18: 1 (20.68, 61.17 and 41.72 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively), −C18: 2 (61.49, 19.55 and 42.13 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively) and −C18: 3 (60.89, 60.16 and 1.53 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively). Dry matter intake and lactose content were not affected by the treatments, but the milk protein content was lower in cows treated with −C18: 2 than that in CTL-treated cows. Milk yield as well as milk fat, protein and lactose yields were higher in cows treated with −C18: 3 than the yields in CTL-treated cows, and these yields increased linearly as the unsaturation degree of the supplemental FA decreased. Compared with the CTL treatment, the −C18: 2 treatment decreased milk C18: 2 cis-9 content (by 2.80%) and yield (by 22.12 g/day), and the −C18: 3 treatment decreased milk C18: 3 cis-9, cis-12, cis-15 content (by 2.72%) and yield (by 22.33 g/day). In contrast, removing C18: 1 cis-9 did not affect the milk content or yield of C18: 1 cis-9. The −C18: 2-treated cows had a higher C18: 1 cis-9 content and tended to have a higher C18: 1 cis-9 yield than CTL-treated cows. The yields of C8: 0, C14: 0 and C16: 0 as well as <C16: 0 tended to increase linearly as the unsaturation degree of the supplemental FA decreased (P=0.06, 0.07, 0.07 and 0.09, respectively). These results indicated that supplementation with C18 unsaturated FA might not independently affect the lactation performance and the milk FA profile of dairy cows.     

The effect of trans-10, cis-12 conjugated linoleic acid on gene expression profiles related to lipid metabolism in human intestinal-like Caco-2 cells

We conducted an in-depth investigation of the effects of conjugated linoleic acid (CLA) on the expression of key metabolic genes and genes of known importance in intestinal lipid metabolism using the Caco-2 cell model. Cells were treated with 80 μmol/L of linoleic acid (control), trans-10, cis-12 CLA or cis-9, trans-11 CLA. RNA was isolated from the cells, labelled and hybridized to the Affymetrix U133 2.0 Plus arrays (n = 3). Data and functional analysis were preformed using Bioconductor. Gene ontology analysis (GO) revealed a significant enrichment (P < 0.0001) for the GO term lipid metabolism with genes up-regulated by trans-10, cis-12 CLA. Trans-10, cis-12 CLA, but not cis-9, trans-11 CLA, altered the expression of a number of genes involved in lipid transport, fatty acid metabolism, lipolysis, β-oxidation, steroid metabolism, cholesterol biosynthesis, membrane lipid metabolism, gluconeogenesis and the citrate cycle. These observations warrant further investigation to understand their potential role in the metabolic syndrome.     

Complex of cis-(NH3)2PtCl2 with guanylyl(3′-5′)-cytidine

The predominant complex formed by the reaction of cis-(NH₃)₂PtCl₂ and guanylyl(3′-5′)cytidine has been isolated. The molar ratio of the binding of cis-(NH₃)₂PtCl₂ to guanylyl(3′-5′)-cytidine is 1:2. The values of proton dissociation constant due to guanine and cytosine bases provide useful information for determining the binding site of the isolated complex. In addition, nmr and ir spectral data were used to determine the binding site. cis-(NH₃)₂PtCl₂ coordinates to guanylyl(3′-5′)cytidine through N(7) position of the guanine base, but cytosine base does not participate in the binding to cis-(NH₃)₂Pt²⁺. Interbase crosslink has not been detected. The binding specificity of cis-(NH₃)₂PtCl₂ to guanine base is discussed.     

On the non-existence of eloxanthin

Abandonment of the name eloxanthin is proposed. The principal carotenoids in various species of Elodea were (3R, 3′R, 6′R)-lutein (β,ε-carotene-3, 3′-diol) and β, β-carotene. The minor pigments were neoxanthin-X (5′, 6′-epoxy-6, 7-didehydro-5, 6, 5′, 6′-tetrahydro-β, β-carotene-3, 5, 3′-triol), 9′-cis-neoxanthin- X, 9- and 13-cis-violaxanthin (5, 6, 5′, 6′-diepoxy-5, 6, 5′, 6′-tetrahydro-β, β-carotene-3, 3′-diol), antheraxanthin (5, 6-epoxy-5, 6-dihydro-β, β-carotene-3, 3′-diol), neolutein A (13- or 13′-cis-lutein) and neolutein B (9- or 9′-cis-lutein). All attempts to isolate eloxanthin failed.     

Chemical constituents from Potentilla fragarioides L

Phytochemical investigation on Potentilla fragarioides L. has led to the identification of twelve compounds including β-sitosterol (1), β-daucosterol (2), ursolic acid (3), pomolic acid (4), swinhoeic acid (5), (1-p-hydroxy-cis-cinnamoyl)cinnamic acid (6), trans-caffeoylisocitric acid (7), trans-caffeic acid (8), quercetin (9), quercetin-3-O-β-D-glucuronide (10), (+)-catechin (11) and 3-O-methylellagic acid-4′-O-ɑ-L-rhamnopyranoside (12). Among them, compounds 4–7 were first identified from the genus Potentilla. And the other compounds except compounds 8 and 11 were found in Potentilla fragarioides for the first time. Chemotaxonomic significance of these compounds was discussed.     

Pyranocoumarin derivatives from Seseli tortuosum

Trans-khellactone, cis-khellactone, 3′-senecioyl-cis-khellactone, 3′-senecioyl-4′-acetyl-cis-khellactone, 4′-senecioyl-cis-khellactone, 3′-acetyl-4′-senecioyl-cis-khellactone, 3′,4′-di-isovaleryl-cis-khellactone, 3′,4′-disenecioyl-cis-khellactone, 3′-angeloyl-4′-isovaleryl-cis-khellactone and 3′-isovaleryl-4′-angeloyl-cis-khellactone were obtained from the aerial part of Seseli tortuosum.     

Effect of pH on conjugated linoleic acid (CLA) formation of linolenic acid biohydrogenation by ruminal microorganisms

Conventional beliefs surrounding the linolenic acid (LNA; cis-9 cis-12 cis-15 C18:3) biohydrogenation (BH) pathway propose that it converts to stearic acid (SA) without the formation of conjugated linoleic acid (CLA) as intermediate isomers. However, an advanced study (Lee and Jenkins, 2011) verified that LNA BH yields multiple CLAs. This study utilized the stable isotope tracer to investigate the BH intermediates of ¹³C-LNA with different pH conditions (5.5 and 6.5). The ¹³C enrichment was calculated as a ¹³C/¹²C ratio of labeled minus unlabeled. After 24 h, eight CLA isomers were significantly enriched on both pH treatment, this result verifies that these CLAs originated from ¹³C-LNA BH which supports the results of Lee and Jenkins (2011). The enrichment of cis-cis double bond CLAs (cis-9 cis-11 and cis-10 cis-12 CLA) were significantly higher at low pH conditions. Furthermore, the concentration of cis-10 cis-12 CLA at low pH was four times higher than at high pH conditions after a 3 h incubation. These differences support the LNA BH pathways partial switch under different pH conditions, with a strong influence on the cis-cis CLA at low pH. Several mono-, di-, and tri-enoic fatty acid isomers were enriched during 24 h of incubation, but the enrichment was decreased or restricted at low pH treatment. Based on these results, it is proposed that low pH conditions may cause a changed or limited capacity of the isomerization and reduction steps in BH.     

Occurrence of 15-cis-violaxanthin in Viola tricolor

A new cis isomer in the violaxanthin series has been isolated from the blossoms of Viola tricolor and identified by MS, IR and UV as the central-monocis form. It was converted to all-trans-violaxanthin by stereomutation. The CD correlation between 15-cis-violaxanthin and natural violaxanthin (5,6,5′,6′-diepoxy-5,6,5′,6′-tetrahydro- β,β-caroten-3,3′-diol) provided the basis for assignment of the absolute configurations 3S, 5R, 6S, 3′S, 5′R, 6′S. Trans—cis isomerization of all-trans-violaxanthin also resulted in 15- cis-violaxanthin. In addition a quantitative determination of the carotenoids was conducted.     

Synthesis and evaluation of (E)-2-(acrylamido)cyclohex-1-enecarboxylic acid derivatives as HCA1, HCA2, and HCA3 receptor agonists

2-(3-(Naphthalen-2-yl)propanamido)cyclohex-1-enecarboxylic acid and its 6-hydroxynaphthalen-2-yl analogue are well-known hydroxyl-carboxylic acid (HCA) receptor HCA2 agonists. A series of novel aryl derivatives of 2-amidocyclohex-1-ene carboxylic acid that contained rigidity elements, such as an E-double bond, triple bond, and trans or cis-substituted cyclopropane rings, instead of the saturated ethane linker in the amide part of the molecules were designed and synthesized, and the derivatives’ potency for the activation of HCA1, HCA2, and HCA3 receptors by 3′–5′-cyclic adenosine monophosphate (cAMP) assay were evaluated. The SAR studies revealed that the rigidifying of appropriate molecules enabled modulation of the potency and selectivity of the HCA2 receptor activation.     

Quantitative determination of diol metabolites of CS-670, a new antiinflammatory agent,by capillary column gas chromatography-mass spectrometry

CS-670(I), being developed as a non-steroidal anti-inflammatory agent, is a racemic prodrug. It has been found to be readily metabolized to active metabolites: trans and unsaturated mono-ols (trans-OH, unsaturated-OH). We report here a method for the quantitative determination of the eight diol stereoisomers excreted in urine after administration I. The diols were well separated and quantitated using capillary column GC-MS after a rather simple derivatization with diazomethane-trifluoroacetic anhydride. Sex differences in rats and species differences between rats and mice were observed in the metabolism of I: the trans-diols originating from trans-OH were predominantly excreted in male and female rat urine but the excretion rate was greater in the male rats; the cis-diols originating from cis mono-ol (cis-OH) were the major urinary metabolites in mice. The hydroxy groups were mainly introduced at the respective equatorial hydrogen atoms at the 4′-carbon of trans-OH and the 5′-carbon of cis-OH. The 4′- and 5′-hydroxy groups in the diols were in the cis conformation with respect to the original 2′-hydroxy group. As approximately 9% of the trans-diols were excreted in urine after administration of cis-OH to rats, the chiral inversion from cis-OH to trans-OH was suggested to occur through the saturated ketone intermediate.     

Formation of 12-oxo-trans-10-dodecenoic acid in chloroplasts from Thea sinensis leaves

Linolenic acid-[1-¹⁴C] was converted to 12-oxo-trans-10-dodecenoic acid, via 12-oxo-cis-9-dodecenoic acid by incubation with chloroplasts of Thea sinensis leaves. Thus, it was confirmed that linolenic acid is split into a C₁₂-oxo-acid, 12-oxo-trans-10-dodecenoic acid, and a C₆-aldehyde, trans-2-hexenal, leaf aldehyde, by an enzyme system in chloroplasts of tea leaves.