Configuration of the carotenoid in the reaction centers of photosynthetic bacteria. Comparison of the resonance Raman spectrum of the reaction center of Rhodopseudomonas sphaeroides G1C with those of cis-trans isomers of β-carotene

The resonance Raman spectrum of the reaction center of Rhodopseudomonas sphaeroides G1C as well as those of the cis-trans isomers of β-carotene (all-trans, 9-cis, 13-cis, 15-cis and 9-cis, 13-cis- (or 9-cis, 13′-cis)) have been recorded at liquid N₂ temperature by use of the 457.9, 488.0 and 514.5 nm excitation lines. Comparison of the spectra indicated that the carotenoid in the reaction center takes the 15-cis configuration.     

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.     

Phenylpropanoid amides from Alisma orientalis and their protective effects against H2O2-induced damage in SH-SY5Y cells

Five new phenylpropanoid amides, including N-trans-feruloyl-N′-cis-feruloyl-cadaverine (1), N,N′-trans-diferuloyl-3-oxo-cadaverine (2), N-trans-feruloyl-N′-cis-feruloyl-3-hydroxy-cadaverine (3), N,N′-cis-diferuloyl-3-hydroxy-cadaverine (4), N-trans-p-coumaroyl-N′-trans-feruloyl-3-hydroxy-cadaverine (5), were isolated from Alisma orientalis together with four known analogues. Their structural elucidations were conducted by using 1D and 2D NMR and HRESIMS spectroscopic analyses. The isolated compounds were assayed for their inhibitory activities against HCE-2, anti-oxidant effects, and their protective effects on H₂O₂-induced damage in human dopaminergic neuroblastoma cells (SH-SY5Y). Compounds 3, 6, and 7 displayed moderate anti-oxidant activities with IC₅₀ values in the range of 36.9–40.7 μM. Compound 5 showed significant protective activity, while compounds 1, 2, 4, 7, and 8 showed moderate protective activities.     

(−)-Epilamprolobine and its N-oxide,lupin alkaloids from Sophora tomentosa

From the fresh leaves of Sophora tomentosa, three new lupin alkaloids, (?)-epilamprolobine, (+)-epilamprolobine N-oxide and 5-(3′-methoxycarbonylbutyroyl)aminomethyl-trans-quinolizidine N-oxide, have further been isolated along with (+)-matrine, (+)-matrine N-oxide, (+)-sophocarpine N-oxide, (?)-anagyrine, (?)- baptifoline, (?)-cytisine, (?)-N-methylcytisine, (?)-N-formylcytisine, (?)-N-acetylcytisine and (±)-ammodendrine. The absolute configurations of (+)-epilamprolobine N-oxide (1R:5R:6S) and (?)-epilamprolobine (5R:6S) have also been established by spectroscopic data and by comparison with synthetic (+)-epilamprolobine (5S:6R)derived from (?)-lupinine (5R:6R). (?)-Epilamprolobine is a diastereomer of (+)-lamprolobine (5R:6R) in Lamprolobium fruticosum and 5-(3′-methoxycarbonylbutyroyl) aminomethyl-trans-quinolizidine N-oxide is presumed to be an artefact. A biosynthetic pathway for the formation of (?)-epilamprolobine is also proposed.     

The protoberberine alkaloids of Stephania suberosa

Six new protoberberines were found in Stephama suberosa root extracts: (−)-tetrahydrostephabine, (−)-stephabinamine, stephabine, 8-oxypseudopalmatine, (−)-trans-xylopinine N-oxide and (−)-cis-xylopinine N-oxide. Ten known alkaloids were also detected: (−)-tetrahydropalmatine, (−)-tetrahydropalmatrubine, (−)-stepholidine, (−)-kikemanine, (−)-capaurimine, (−)-coreximine, (−)-corytenchine, (−)-discretine, pseudopalmatine and (−)-xylopinine.     

Evidence for a 13,14-Cis Cycle in Bacteriorhodopsin

We discuss to what extent the vibrational spectra of bacteriorhodopsin that have been observed and assigned by Smith et al. (1, 2) by means of resonance Raman and by Gerwert and Siebert (EMBO (Eur. Mol. Biol. Organ.) J. In press) by means of infrared absorption experiments are in agreement with a photo-cycle of bacteriorhodopsin that involves the sequence BR, IO(all-trans) → K(13,14-cis) → L(13,14-cis) → M(13-cis) → N(13-cis) → O(all-trans). Our discussion is based on a quantumchemical modified neglect of diatomic overlap [MNDO] calculation of the vibrational spectra of the relevant isomers of the protonated retinal Schiff base. In particular, we investigated in these calculations the effects of different charge environments on the frequencies of the relevant C-C single bond stretching vibrations of these isomers.     

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.     

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.     

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.     

4′-Aza-3′,5′-dihomothymidine and Derivatives

Abstract

A series of 3′-branched 4′-azanucleoside analogues have been prepared. These compounds comprise three asymmetric atoms, two carbons and one nitrogen. They constitute nucleoside analogues imparted with a “flickering configuration”, the nitrogen inversion replacing a D-L epimerization of their natural congeners. The 1′,3′-cis and 1′,3′-trans isomers have been separated and their configuration established by ¹H NMR and the X-ray diffraction structure of one crystalline example. The configurations of the frozen invertomers were assessed by low temperature ¹H NMR experiments assisted by molecular mechanics simulations. None of these compounds exhibited any significant in vitro antiviral activity.     

Comparative metabolism of the cis and trans isomers of N-nitroso-2-6-dimethylmorpholine in rats,hamsters and guinea pigs

The in vivo metabolism of the cis and trans isomers of N-[3,5-³H] nitroso-2,6-dimethylmorpholine (NDMM) was studied in female Fischer rats, Syrian golden hamsters and guinea pigs by analysis of urinary metabolites using high pressure liquid chromatography (HPLC). Animals were treated by gavage with 12 mg/kg body wt. of NDMM, composed of both isomers and 12 μCi/kg body wt. of either of the separated radioactive isomers (cis or trans). Control animals received 12 mg, 12 μCi/kg body wt. NDMM with both isomers labeled in their natural proportion.There was a substantial increase in the excretion of a particular metabolite, 2-(2-hydroxyl-methyl)ethoxy propanoic acid, in the urine of rats, hamsters and guinea pigs 24 h after received the trans isomer (24, 22 and 13% of the total dose excreted, respectively). A minor metabolite was determined to be 2,6-dimethylmorpholine-3-one, another product of α-oxidation. The metabolite 1-amino-2-hydroxypropanol was identified, indicating that NDMM was metabolized by both α-and β-oxidation.In all three species, animals administered the cis isomer excreted larger amounts of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) and N-nitroso-bis(2-hydroxypropyl)amine (BHP) products of beta oxidation, than those treated with the trans isomer. Hamsters and guinea pigs treated with the more carcinogenic cis isomer in these species, also excreted twice as much of two other metabolites than was found in the urine of animals given the trans isomer.The trans isomer of NDMM appeared to be preferentially metabolized by α-oxidation and from earlier studies this metabolic pathway seemed to be important in carcinogenesis by NDMM in the rat. The cis isomer might be in a conformation more favorable for β-oxidation and this pathway may be of primary importance in carcinogenesis by NDMM in hamsters and guinea pigs.     

Transmembrane localization of cis-isomers of zeaxanthin in the host dimyristoylphosphatidylcholine bilayer membrane

The effects of the 9-cis and 13-cis isomers of zeaxanthin on the molecular organization and dynamics of dimyristoylphosphatidylcholine (DMPC) membranes were investigated using conventional and saturation recovery EPR observations of the 1-palmitoyl-2-(14-doxylstearoyl)phosphatidylcholine (14-PC) spin label. The results were compared with the effects caused by the all-trans isomer of zeaxanthin. Effects on membrane fluidity, order, hydrophobicity, and the oxygen transport parameter were monitored at the center of the fluid phase DMPC membrane. The local diffusion-solubility product of oxygen molecules (oxygen transport parameter) in the membrane center, studied by saturation-recovery EPR, decreased by 47% and 27% by including 10 mol% 13-cis and 9-cis zeaxanthin, respectively; whereas, incorporation of all-trans zeaxanthin decreased this parameter by only 11%. At a zeaxanthin-to-DMPC mole ratio of 1:9, all investigated isomers decreased the membrane fluidity and increased the alkyl chain order in the membrane center. They also increased the hydrophobicity of the membrane interior. The effects of these isomers of zeaxanthin on the membrane properties mentioned above increase as: all-trans < 9-cis ≤ 13-cis. Obtained results suggest that the investigated cis-isomers of zeaxanthin, similar to the all-trans isomer, are located in the membrane interior, adopting transmembrane orientation with the polar terminal hydroxyl groups located in the opposite leaflets of the bilayer. However, the existence of the second pool of cis-zeaxanthin molecules located in the one leaflet and anchored by the terminal hydroxyl groups in the same polar headgroup region cannot be completely ruled out.     

cis–trans isomerization of carbon double bonds in monounsaturated triacylglycerols via generation of free radicals

We investigated the heat-induced cis/trans isomerization of double bonds in monounsaturated lipids. When triolein (9-cis, 18:1) was heated around 180 °C, small amounts of isomerization products were obtained depending on the heating period. The heat-induced isomerization of triolein was considerably suppressed by the addition of different antioxidants or under nitrogen stream, and these additives simultaneously inhibited the thermal oxidation of double bonds in triolein. Therefore, an intermediate of the thermal oxidation reaction might be responsible for the heat-induced isomerization of the double bonds in triolein. The thermodynamics of the heat-induced isomerization of triolein (9-cis, 18:1) and trielaidin (9-trans, 18:1) were investigated using Arrhenius plot. The Arrhenius activation energies of cis double bonds in triolein and trans double bonds in trielaidin were 106 kJ/mol and 137 kJ/mol, respectively. The calculated internal rotational barrier heights of these double bonds were similar to those of the double bond of 2-butene radical and significantly lower than those of non-radicalized double bonds in 2-butene. These results suggest that heat-induced cis/trans isomerization of triolein and trielaidin occurs mainly through the formation of radical species, which are the intermediates produced during thermal oxidation. The activation energy difference between the two forms suggests that trans trielaidin radicals are more stable than cis triolein radicals. The high thermodynamic stability of the trans double bonds in lipid radicals would influence the population of cis and trans isomers in edible oils and contribute to slight accumulation of trans-18:1 isomers during heating or industrial processing.     

Alkaloids from trunk bark of Hernandia nymphaeifolia

Six new alkaloids, (+)-ovigerdimerine, 4-methoxyoxohernandaline, 7-formyldehydrohernangerine, 5,6-dimethoxy-N-methylphthalimide, 7-hydroxy-6-methoxy-1-methylisoquinoline and (+)-vateamine-2′-β-N-oxide, along with one new dialdehyde, hernandial, have been isolated and characterized from the trunk bark of Hernandia nymphaeifolia. The structures of these compounds were elucidated by spectral analyses.     

9-cis-canthaxanthin exhibits higher pro-apoptotic activity than all-trans-canthaxanthin isomer in THP-1 macrophage cells

All-trans-canthaxanthin (4, 4′-diketo β-carotene) but not 9-cis-canthaxanthin has been shown to induce apoptosis in some cell lines. In this study apoptotic activity of 9-cis-canthaxanthin on THP-1 macrophage is reported. Comparison of apoptotic activities of the two canthaxanthin isomers on this cell line by annexin V-cy3 and TUNEL assays indicated the higher pro-apoptotic activity of 9-cis-isomer than the all-trans-isomer. Canthaxanthin-induced apoptosis in this cell line was found to be accompanied by increased caspase-3 and caspase-8 activities, indicating its progression via caspase cascade. Induction of both caspase activities was higher by 9-cis-canthaxanthin than that by trans-canthaxanthin. All these results suggest that canthaxanthin stereoisomers differentially induce apoptosis of THP-1 monocyte/macrophage.     

8-O-methyl- and the first 3-O-methylflavan-3,4-diols from Acacia saxatilis

The light purple heartwood of Acacia saxatilis contains (+)-2,3-trans-3,4-trans- and (+)-2,3-trans-3,4-cis-diastereoisomers of 8-methoxy-7,j',4'-trihydroxy- and 7,3′,4′-trihydroxyflavan-3,4-diols as major components. Evidence was also obtained of the first 3-methyl ether of metabolites: of this type, notably of (+)-8-methoxy-7,3′,4′-trihydroxy-2,3-trans-flavan-3,4-cis-diol. Flavonol, dihydroflavonol and flavanone analogies accompany these. The correlation between colour of Acacia heartwoods and structure, phenolic substitution, stereochemistry and composition of their flavonoid components is discussed.     

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.     

N′-isopropylnornicotine: Its formation from nicotine in aged leaves of Nicotiana tabacum

An aqueous solution of nicotine-[2′-¹⁴C] was painted on the leaves of 4-month-old tobacco plants (Nicotiana tabacum) which were harvested 3 weeks later. This tracer was similarly applied to excised tobacco leaves which were allowed to dry in air for 4 weeks. The alkaloids, were extracted with the addition of N′-isopropylnornicotine, a compound which has been previously isolated from air-cured tobacco. Radioactive nicotine and nornicotine were isolated from the intact plants with only minute activity in the N′-isopropylnornicotine. All three of these alkaloids were radioactive from the air-cured leaves, and degradation of the labelled N'-isopropylnornicotine indicated that all the activity was located at the C-2′ position. A higher level of activity was found in N′-isopropylnornicotine which was obtained from excised leaves which were fed the nicotine- [2′- ¹⁴C] in aqueous acetone, and were treated on subsequent days with aqueous acetone. These results are consistent with the hypothesis that N′-isopropylnornicotine is produced in the curing of tobacco leaves by reaction of nornicotine (formed by the demethylation of nicotine) with acetoacetate, followed by decarboxylation and reduction. The ¹³C NMR chemical shifts of the methyl groups of N′-isopropylnornicotine and related 1-isopropylpyrrolidines which have chirality at the α-position of the pyrrolidine ring, are significantly different (up to 7.5 ppm).     

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.