(+)-11-oxocytisine,a lupin alkaloid from leaves of sophora secundiflora

A new lupin alkaloid, (+)-11-oxocytisine (1), was isolated from the leaves of Sophora secundiflora together with (−)-anagyrine, (−)-N-methylcytisine, (−)-baptifoline, (−)-N-formylcytisine, (−)-N-acetylcytisine and (−)-cytisine. The structure of the new alkaloid (1) was presumed to be (+)-11--oxocytisine on the basis of its spectroscopic data.     

(−)-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.     

Nicotine N-oxides

Nicotine-1-N-oxide, trans and cis isomers of nicotine-1′-N-oxide and of nicotine-1,1′-di-N-oxide have been prepared and characterised by NMR, MS and reduction to nicotine. The trans and cis isomers of nicotine-1′-N-oxide have been identified in leaves, stems and roots of Nicotiana tabacum, N. affinis and N. sylvestris.     

Spectral evidence for the formation of active intermediates from RuCl3 and RuCl2(PPh3)3 with N-methylmorpholine N-oxide (NMO) and phenyliodosoacetate (PIA) as mild oxidants

Electronic, EPR and IR spectral evidence are given for the formation of the following active species: (1) ruthenium(VIII) in ruthenium(III)-PIA system, (2) ruthenium(V) oxo species in ruthenium(III)-N- oxide system, and (3) ruthenium(II)-phosphine oxide complex in ruthenium(II) N-oxide system. Cyclic voltammetric studies also suggest the formation of Ru(V) in ruthenium(III)-N-oxide system.     

Megastigmane and 7,9′-dinorlignan glycosides from the tubers of Stephania kaweesakii

Two isomers of megastigmane glycosides, (6R, 9S)-blumenol C 9-O-gentibioside (2) and (6S, 9S)-blumenol C 9-O-gentiobioside (3), and a new 7,9′-dinorlignan glycoside, stepdonorlignoside (4) were isolated from the tubers of Stephania kaweesakii. The structure determinations were considered based on the physical data and spectroscopic evidence. The absolute configurations of two megastigmanes were determined for the first time. Additionally, ten known compounds were isolated: (6R, 9S)-blumenol C 9-O-β-D-glucopyranoside, (+)-isolariciresinol 3a-O-β-D-glucopyranoside, salidroside, N-trans-caffeoyltyramine, (R)-isococlaurine, (R)-isococlaurine 4′-O-β-glucopyranoside, (−)-oblongine, (+)-magnocurarine, fordianoside, and (−)-cyclanoline.     

A sesquiterpene evoninoate alkaloid from Maytenus guianensis

The trunk wood and root of Maytenus guianensis contain 4′-O-methyl-(−)-epigallocatechin, proanthocyanidin A, dulcitol, sitosterol, β-sitostenone and friedelan-3,7-dione. The trunk wood also furnished N,N-dimethylserine. A new sesquiterpene alkaloid, named mayteine, was isolated from the root.     

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.     

Cytochromes of the trimethylamine N-oxide anaerobic respiratory pathway of Escherichia coli

Escherichia coli grown anaerobically with trimethylamine N-oxide (TMAO) as a terminal electron acceptor develops a new cytochrome pathway in addition to the aerobic respiratory pathways which are still formed. Formate, NADH, and possibly other substrates derived from glucose, supply electrons to this pathway. Cytochromes with α-absorption peaks at about 548, 552, 554 and 557 nm are rapidly reoxidized by TMAO in a reaction which is not inhibited by 2-n-heptyl-4-hydroxyquinoneN-oxide. CuSO₄ inhibits the reoxidation by TMAO of the first two of these cytochromes. This suggests that the pathway of electron transfer leading to the reduction of TMAO is: substrates → cytochromes 548,552 → cytochromes 554,557 → trimethylamine-N-oxide reductase → TMAO. These cytochromes, but not those of the aerobic respiratory pathways, are reoxidized by the membrane-impermeant oxidant ammonium persulfate in intact cells. This suggests that the cytochromes of the TMAO reduction pathway and / or trimethylamine-N-oxide reductase are situated at the periplasmic surface of the cytoplasmic membrane of E. coli.     

Six alkaloids from Papaver species

Papaver fugax produced the new alkaloids (−)-narcotinehemiacetal and (−)-papaveroxine. New alkaloids from P. pseudo-orientale are (−)-narcotinediol, (+)-macrantaldehyde, (−)-papaveroxinoline, (−)-narcotolinol and (−)-narcotinehemiacetal.     

In vivo evidence that phenylalanine 171 acts as a molecular brake for translesion DNA synthesis across benzo[a]pyrene DNA adducts by human DNA polymerase κ

Humans possess multiple specialized DNA polymerases that continue DNA replication beyond a variety of DNA lesions. DNA polymerase kappa (Pol κ) bypasses benzo[a]pyrene diolepoxide-N²-deoxyguanine (BPDE-N²-dG) DNA adducts in an almost error-free manner. In the previous work, we changed the amino acids close to the adducts in the active site and examined the bypass efficiency. The substitution of alanine for phenylalanine 171 (F171A) enhanced by 18-fold in vitro, the efficiencies of dCMP incorporation opposite (−)- and (+)-trans-anti-BPDE-N²-dG. In the present study, we established human cell lines that express wild-type Pol κ (POLK+/−), F171A (POLK F171A/−) or lack expression of Pol κ (POLK−/−) to examine the in vivo significance. These cell lines were generated with Nalm-6, a human pre-B acute lymphoblastic leukemia cell line, which has high efficiency for gene targeting. Mutations were analyzed with shuttle vectors having (−)- or (+)-trans-anti-BPDE-N²-dG in the supF gene. The frequencies of mutations were in the order of POLK−/− > POLK+/− > POLK F171A/− both in (−)- and (+)-trans-anti-BPDE-N²-dG. These results suggest that F171 may function as a molecular brake for bypass across BPDE-N²-dG by Pol κ and raise the possibility that the cognate substrates for Pol κ are not BP adducts in DNA but may be lesions in DNA induced by endogenous mutagens.     

Comparative theoretical studies of differently bridged nitramino-substituted ditetrazole 2-<Emphasis Type="Italic">N</Emphasis>-oxides with high detonation performance and an oxygen balance of around zero

In this work, six (A–F) nitramino (–NHNO₂)-substituted ditetrazole 2-N-oxides with different bridging groups (–CH₂–, –CH₂–CH₂–, –NH–, –N=N–, and –NH–NH–) were designed. The six compounds were based on the parent compound tetrazole 2-N-oxide, which possesses a high oxygen balance and high density. The structure, heat of formation, density, detonation properties (detonation velocity D and detonation pressure P), and the sensitivity of each compound was investigated systematically via density functional theory, by studying the electrostatic potential, and using molecular mechanics. The results showed that compounds A–F all have outstanding energetic properties (D: 9.1–10.0 km/s; P: 38.0–46.7 GPa) and acceptable sensitivities (h ₅₀: 28–37 cm). The bridging group present was found to greatly affect the detonation performance of each ditetrazole 2-N-oxide, and the compound with the –NH–NH– bridging group yielded the best results. Indeed, this compound (F) was calculated to have comparable sensitivity to the famous and widely used high explosive 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX), but with values of D and P that were about 8.7% and 19.4% higher than those for HMX, respectively. The present study shows that tetrazole 2-N-oxide is a useful parent compound which could potentially be used in the design of new and improved high-energy compounds to replace existing energetic compounds such as HMX.     

Species differences in the stereoselectivity of N-oxygenation of N-ethyl-N-methylaniline in vitro

The prochiral tertiary amine N-ethyl-N-methylaniline (EMA) is known to be stereoselectively N-oxygenated in the presence of hepatic microsomal preparations. This biotransformation is thought to be mediated predominantly by the flavin-containing monooxygenase (FMO) enzyme system. In order to characterise this reaction further, the in vitro metabolism of EMA in the presence of hepatic microsomal preparations derived from a number of laboratory species has been examined. EMA N-oxide formation was stereoselective with respect to the (−)-S-enantiomer in the presence of microsomal preparations from all species examined, with the degree of selectivity decreasing in the order of rabbit > rat ∼ LACA mouse ∼ DBA/2Ha mouse > guinea-pig > dog. The enantiomeric composition of the metabolically derived EMA N-oxide appeared to be determined solely by the differential rate of formation of the two enantiomers as opposed to any differences in affinities for the substrate in its pro-R and pro-S conformations. The use of enzyme inhibitors, activators and inducers indicated that EMA N-oxide formation was predominantly mediated by FMO in the presence of rabbit hepatic microsomes and that these agents did not generally affect the stereochemical outcome of the biotransformation. © 1996 Wiley-Liss, Inc.     

A pair of new lignan enantiomers from Croton tiglium

A pair of new 3′,7-epoxy-8,4′-oxyneolignan enantiomers [(+)-1 and (−)-1] as well as a known phenylpropanoid (2) were isolated from the seeds of Croton tiglium Linn. Their structures were established based on extensive spectroscopic analyses. The absolute configurations of (+)-1 and (−)-1 were determined by NMR data calculations and electronic circular dichroism calculations. All compounds were isolated from the genus Croton for the first time. Particularly, (+)-1 and (−)-1 were the first 3′,7-epoxy-8,4′-oxyneolignanes reported in Croton. The chemotaxonomic significance of these compounds was discussed.     

Liver metabolic reactions: tertiary amine N-dealkylation, tertiary amine N-oxidation, N-oxide reduction, and N-oxide N-dealkylation. II. N,N-dimethylaniline

Rat liver microsomal preparations enzymatically catalyze the N-demethylation and N-oxidation of dimethylaniline as well as the N-demethylation of dimethylaniline-N-oxide. Both compounds were used as substrates and the formation of formaldehyde and N-oxide were determined.Both demethylation and N-oxidation of dimethylaniline are dependent on NADPH. This cofactor also increases the demethylation of dimethylaniline-N-oxide, although it is not an absolute requirement. Nicotinamide increases the rate of formation of formaldehyde and N-oxide from dimethylaniline by a factor of about 4 and decreases the N-oxide demethylation by the same factor. The cofactor optimum consists of NADPH, nicotinamide, and magnesium ions for the demethylation and N-oxidation of dimethylaniline, and of NADPH alone for the demethylation of its N-oxide. The kinetic constants of the three test reactions have been determined under these optimal cofactor requirements.Various agents strongly influence the rates of product formation of the three test reactions studied. SH-blocking agents, the chelating agent EGTA, as well as nicotinamide influence the rates of formaldehyde formation from dimethylaniline and N-oxide demethylation in an opposite way. This demonstrates that, in the tertiary amine demethylation of dimethylaniline, a C-oxidation pathway is operative in addition to an N-oxidation pathway with subsequent N-oxide demethylation. The following influences on the actual metabolic reactions could be deduced from the effects of agents on the test reactions: SKF 525-A inhibits and phenobarbital pretreatment stimulates N-oxide demethylation; EDTA inhibits both the latter reaction and N-oxidation; EGTA and nicotinamide stimulate C-oxidation and inhibit N-oxide demethylation; SH-blocking agents inhibit C-oxidation and stimulate both N-oxidation and N-oxide demethylation.Quantitative and qualitative species differences with respect to cofactor requirement and effect of SKF 525-A have been observed between rat and pig liver microsomes. In addition, profound differences in subcellular localization and metabolic rates between dimethylaniline and other substrates are known. Thus it is unlikely that the three metabolic reactions dealt with in this report are characteristic of tertiarr amine N-dealkylation in general.     

Two pairs of alkaloid enantiomers from Ganoderma luteomarginatum

A pair of new alkaloid enantiomers [(+)- and (−)-1] as well as a pair of known enantiomeric analogues [(+)- and (−)-2] were isolated from the fruiting bodies of Ganoderma luteomarginatum. Their planar structures were determined by extensive spectroscopic analyses. The absolute configurations were established by comparison of the experimental and calculated electronic circular dichroism (ECD) or comparison of the experimental and reported specific optical rotation ([α]_D). These rare Ganoderma alkaloids have a phenyl-substituted 6,7-dihydro-5H-cyclopenta[c]pyridine skeleton that has only been reported from the genus Ganoderma. The (+)- and (−)-1 were new Ganoderma alkaloids, while (+)- and (−)-2 were isolated from G. luteomarginatum for the first time. Thus, these four isolates could be tentatively determined as chemotaxonomic constituents of G. luteomarginatum.     

Ophiostomatoid fungi can emit the bark beetle pheromone verbenone and other semiochemicals in media amended with various pine chemicals and beetle-released compounds

Fungal volatile compounds can mediate fungal-insect interactions. Whether fungi can emit insect pheromones and how volatile chemicals change in response to chemicals the fungi naturally encounter is poorly understood. We analyzed volatiles emitted by Grosmannia clavigera (symbiont of the mountain pine beetle) and Ophiostoma ips (symbiont of the pine engraver beetle) growing in liquid media amended with compounds that the fungi naturally encounter: (−)-α-pinene, (+)-α-pinene, (−)-trans-verbenol, verbenone, or ipsdienol. Nine volatile compounds were identified among the fungal and amendment treatments. Volatiles qualitatively and quantitatively differed between fungal species and among amendment treatments. The bark beetle anti-aggregation pheromone (−)-verbenone was detected from both fungi growing in (−)-trans-verbenol-amended media. G. clavigera and O. ips can emit beetle pheromones and other beetle semiochemicals, suggesting that ophiostomatoid fungi could contribute to the chemical ecology of bark beetles. However, such contributions could be modulated by the presence of other environmental chemicals.     

Alkaloids inhibiting l-histidine decarboxylase from Sinomenium acutum

Chromatographic separation of an extract of the stems of Sinomenium acutum resulted in the isolation of two new alkaloids, 2-O-demethyl-acutumine (4), and 6-O-methyl-laudanosoline-1-O-glucoside (5), together with three known alkaloids, sinomenine (1), sinomenine N-oxide (2), and magnoflorine (3). Sinomenine was found to show good inhibitory activity toward l-histidine decarboxylase from Lactobacillus 30a with an IC₅₀ value of 969 μM but its N-oxide showed no inhibition of this enzyme. Sinomenine inhibited this enzyme in a noncompetitive manner with a K_i of 762 μM.     

N-oxides of hyoscyamine and hyoscine in the solanaceae

The N-oxides of (−)-hyoscyamine and (−)-hyoscine have been prepared and characterized. Two N-oxides of hyoscyamine have been isolated from species of Atropa,Datura,Hyoscyamus,Scopolia andMandragora,andoneN-oxideofhyoscinehasbeenisolatedfromspeciesofthefirstfourgenera.     

Iridoid and phenylethanoid glycosides from Heterophragma sulfureum

An unusual iridoid diglycoside (specioside 6′-O-α-d-galactopyranoside) and a new phenylethanoid triglycoside (heterophragmoside) were isolated from the leaves and branches of Heterophragma sulfureum together with specioside, verminoside, 6-trans-feruloylcatapol, stereospermoside, (−)-lyoniresinol 3α-O-β-d-glucopyranoside, (+)-lyoniresinol 3α-O-β-d-glucopyranoside, (−)-5′-methoxyisolariciresinol 3α-O-β-d-glucopyranoside, (+)-5′-methoxyisolariciresinol 3α-O-β-d-glucopyranoside, and dehydroconiferyl 4-O-β-d-glucopyranoside. The structural elucidations were based on analyses of chemical and spectroscopic data.     

Oxidation of Elemental Sulfur to Sulfite by Thiobacillus thiooxidans Cells

Thiobacillus thiooxidans cells oxidized elemental sulfur to sulfite, with 1 mol of O₂ consumption per mol of sulfur oxidized to sulfite, when the oxidation of sulfite was inhibited with 2-n-heptyl-4-hydroxyquinoline N-oxide.