Kinetics of nitroxyl radical reactions. A pulse-radiolysis conductivity study.

Absolute rate-constants for the reaction of the nitroxyl free radicals TAN and TMPN with radiation-chemically-formed radicals and ions have been determined. k(TAN + X) (in M(-1) sec(-1)=4-0 X 10(9) (for X = OH-), 2-9 X 10(10) (eaq-), 8-0 X 10(9) (H-), 7-2 X 10(8) (-CH2OH), 4-0 X 10(8) (CH3CHOH), 4-3 X 10(8) ((CH3)2COH) 2-8 X 10(8) (-CH2(CH3)2COH), 5-9 X 10(7) (glucose radical), 4-0 X 10(8) (c-C5H9-), and k(TMPN + X)=3-4 X 10(9) (OH-), 7-8 X 10(9) (eq-), 4-9 X 10(9) (H-), 4-4 X 10(8) (-CH2OH), 4-9 X 10(8) (CH3CHOH), 3-6 X 10(8) ((CH3)2COH), 1-5 X 10(8) (-CH2(CH3)2COH), 4-9 X 10(7) (glucose radical), 4-3 X 10(8) (c-C5H9-). Direct measurements by means of a pulse-radiolysis conductivity technique were based on the formation and destruction of charged species in these reactions within certain pH ranges. It is indicated that the radiosensitizing nitroxyls undergo both redox and addition reactions.     

Hydroperoxide-dependent epoxidation of unsaturated fatty acids in the broad bean (Vicia faba L.)

Incubation of linoleic acid with the 105,000g particle fraction of the homogenate of the broad bean (Vicia faba L.) led to the formation of the following products: 13(S)-hydroxy-9(Z),11(E)-octadecadienoic acid, 9,10-epoxy-12(Z)-octadecenoic acid (9(R),10(S)/9(S)/10(R), 80/20), 12,13-epoxy-9(Z)-octadecenoic acid (12(S),13(R)/12(R)/13(S), 64/36), and 9,10-epoxy-13(S)-hydroxy-11(E)-octadecenoic acid (9(S),10(R)/9(R),10(S), 91/9). Oleic acid incubated with the enzyme preparation in the presence of 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid or cumene hydroperoxide was converted into 9,10-epoxyoctadecanoic acid (9(R),10(S)/9(S),10(R), 79/21). Two enzyme activities were involved in the formation of the products, an omega 6-lipoxygenase and a hydroperoxide-dependent epoxygenase. The lipoxygenase, but not the epoxygenase, was inhibited by low concentrations of 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid. In contrast, the epoxygenase, but not the lipoxygenase, was readily inactivated in the presence of 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid. Studies with 18O2-labeled 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid showed that the epoxide oxygens of 9,10-epoxyoctadecanoic acid and of 9,10-epoxy-13(S)-hydroxy-11(E)-octadecenoic acid were derived from hydroperoxide and not from molecular oxygen.     

湖北旋覆花化学成分的研究(英文)

从湖北旋覆花(Inula hupehensis)地上部分分离得到19个化合物,经波谱数据分析分别鉴定为9-羟基-百里香酚(1),8,10-去氢-β-羟基-百里香酚(2),2-羟基-4-甲基苯乙酮(3),8,9-双羟基-9-百里香酚(4),10-羟基-8,9-双氧亚异丙基百里香酚(5),8,10-二羟基-9-异丁酰百里香酚(6),8-羟基-9-异丁酰-10-(2-甲基丁酰)百里香酚(7),8,9,10-三羟基百里香酚(8),8-羟基-9,10-二异丁酰百里香酚(9),neoechinulin A(10),3-醛基吲哚(11),3-羟乙酰基吲哚(12),丁香酸(13),4,6-二羟基-2-甲氧基苯乙酮(14),7-甲氧基-8-羟基香豆素(15),6-甲氧基山奈酚(16),(+)-正丁香酯素(17),β-棕榈精(18)和豆甾醇(19)。除了化合物8和9外,其他化合物均为首次从该植物中分离得到。     

Identification of the molecular species of lysophosphatidic acid produced when platelets are stimulated by thrombin

Platelets, when stirred with 3 U thrombin/10(9) platelets, produced significant quantities of palmitoyllysophosphatidic acid (2.17 ng/10(9) platelets), stearoyllysophosphatidic acid (2.11 ng/10(9) platelets), and arachidonoyllysophosphatidic acid (1.06 ng/10(9) platelets). When platelets were pretreated with 100 microM of the phospholipase A2 inhibitor U10029A, there was a significant decrease in thrombin-stimulated production of stearoyllysophosphatidic acid (to 0.16 ng/10(9) platelets), while arachidonoyllysophosphatidic acid production was unchanged. U10029A concomitantly increased thrombin-stimulated production of stearoyl-containing phosphatidic acid species (primarily stearoylarachidonoylphosphatidic acid) from 5.99 to 9.71 ng/10(9) platelets. The results are consistent with the concept that stearoyllysophosphatidic acid production in platelets occurs via phospholipase A2 degradation of phosphatidic acid.     

New 11(15-->1)abeotaxane, 11(15-->1),11(10-->9)bisabeotaxane and 3,11-cyclotaxanes from Taxus yunnanensis

Chemical examination of the seeds of Chinese yew, Taxus yunnanensis Cheng et L. K. Fu resulted in the isolation of an 11(15-->1)abeotaxane, an 11(15-->1), 11(10-->9)bisabeotaxane and two 3,11-cyclotaxanes. The structures of these new taxoids were established as 13alpha-acetoxy-5alpha-cinnamoyloxy-11(15-->1)abeotaxa-4(20),11-diene-9alpha,10beta,15-triol (1), 20-acetoxy-2alpha-benzoyloxy-4alpha, 5alpha, 7beta, 9alpha, 13alpha-pentahydroxy-11(15-->1), 11(10-->9) bisabeotax-11-eno-10,15-lactone (2), 2alpha,10beta-diacetoxy-5alpha-cinnamoyloxy-9alpha-hydroxy-3,11 -cyclotax-4(20)-en-13-one (3) and 10beta-acetoxy-2alpha,5alpha,9alpha-trihydroxy-3,11-cyclotax-4(20)-en-13-one (4) on the basis of spectral analyses.     

Quantitative analysis of the elemental composition and the mass of bacterial polyphosphate bodies using STEM EDX

The quantitative analysis of laboratory grown organisms (Plectonema boryanum and Staphylococcus aureus) revealed that a typical in vivo polyphosphate body (PPB) contains O (4.3 x 10(-8) microg), C (1.2 x 10(-8) microg), P (6.7 x 10(-9) microg), Mg (1.3 x 10(-9) microg), Ca (6.7 x 10(-10) microg), K (6.7 x 10(-10) microg), Fe (6.0 x 10(-10) microg), S (5.4 x 10(-10) microg) and Al (5.9 x 10(-10) microg). Quantitative X-ray analysis of samples from nature showed PPB contain O (1.63 x 10(-8) microg), C (4.75 x 10(-9) microg), P (2.50 x 10(-9) microg), Mg (5.0 x 10(-10) microg), Ca (2.50 x 10(-10) microg), K (2.50 x 10(-10) microg), Fe (2.25 x 10(-10) microg) and S (2.0 x 10(-10) microg). The mass of an average polyphosphate body was 6.7 x 10(-8) microg for P. boryanum, 2.5 x 10(-8) microg for S. aureus and for microbes from the natural environment 6.3 x 10(-8) microg. The results indicate that the PPB may have other unknown functions in addition to essential element storage, acting as a detoxification method by sequestering heavy metals and providing a homeostasis system in the cell.     

灵芝液态深层发酵产物中10种不饱和脂肪酸类化合物的鉴定

通过规模化液态深层发酵获得灵芝发酵产物,采用多种硅胶色谱柱层析及重结晶的方式,从中分离得到10个化合物。通过核磁、质谱等波谱分析,鉴定出这些化合物均属于含羟基或酮基的不饱和脂肪酸类化合物,分别为(9S,10R,11E,13R)-9,10,13-trihydroxyoctadec-11-enoic acid（1）和(9S,10R,11E,13S)-9,10,13-trihydroxyoctadec-11-enoic acid（2）的混合物、12S^*,13S^*-dihydroxy-9-oxo-10(E)- octadecenoic acid（3）、9R*,10R*-dihydroxy-13-oxo-11(E)-octadecenoic acid（4）、12S*,13R*-dihydroxy- 9-oxo-10(E)-octadecenoic acid（5）、9S*,10R*-dihydroxy-13-oxo-11(E)-octadecenoic acid（6）、10(S)-hydroxy-8(Z)-octadecenoic acid（7）、12-oxooctadeca-8,10-dienoic acid（8）、9,12-dihydroxy-10-eicosenoic acid（9）和9-oxooctadeca-10,12-dienoic acid（10）。这些化合物均为首次从灵芝发酵产物中获得,且具有不同程度的体外抗肿瘤活性。其中,化合物8和化合物10对L1210细胞增殖抑制的IC₅₀值分别为13.00μmol/L和16.88μmol/L,对K562细胞增殖亦有良好的抑制效果,是具有抗肿瘤潜力的天然产物。     

Synthesis,structure elucidation,and chemiluminescent activity of new 9-substituted 10-(ω-(succinimidyloxycarbonyl)alkyl)acridinium esters

Several new acridinium esters 2 – 9 having their central acridinium ring bearing a 9-(2,5-dimethylphenoxycarbonyl), 9-(2,6-bis(trifluoromethyl)phenoxycarbonyl) or 9-(2,6-dinitrophenoxycarbonyl) group, and a 10-methyl, 10-(3-(succinimidyloxycarbonyl)propyl), 10-(5-(succinimidyloxycarbonyl)pentyl), or 10-(10-(succinimidyloxycarbonyl)decyl) group, have been synthesized and their chemiluminescent properties have been tested. The 2,5-dimethylphenyl acridinium esters emit light slowly (glow) when treated with alkaline hydrogen peroxide, while the 2,6-dinitrophenyl and 2,6-bis(trifluoromethyl)phenyl esters emit light rapidly (flash). The substituent at the 10 position affects the hydrolytic stabilities of the compounds.     

Aromadendrane transformations by Curvularia lunata ATCC 12017

The naturally occurring sesquiterpene squamulosone (1), isolated from Hyptis verticillata (Labiatae), was synthetically reduced to five analogues that were identified as (1S,10S)-9alpha-hydroxy-allo-aromadendrane (2), (1R,10R)-9beta-hydroxyaromadendrane (3), (1S,10S)-allo-aromadendran-9-one (4), (1R,10R)-aromadendran-9-one (5) and aromadendra-1,9-diene (6). Each congener was incubated with the fungus Curvularia lunata ATCC 12017 in two different growth media. All the substrates except the deoxy compound 6 underwent a simple redox reaction. Ketone 5 additionally experienced remote hydroxylation while analogue 6, possessing a conjugated diene system, was most extensively metabolised. The substrates and products presented here, but one, are all novel.     

(+)-12alpha-Hydroxysophocarpine, a new quinolizidine alkaloid and related anti-HBV alkaloids from Sophora flavescens

(+)-12alpha-Hydroxysophocarpine (8), a new quinolizidine alkaloid was isolated from the roots of Sophora flavescens, together with 10 known quinolizidine alkaloids, (+)-oxymatrine (1), (+)-matrine (2), (+)-9alpha-hydroxymatrine (3), (+)-allomatrine (4), (+)-oxysophocarpine (5), (-)-sophocarpine (6), (-)-9alpha-hydroxysophocarpine (7), (+)-lehmannine (9), (-)-13,14-dehydrosophoridine (10), and (-)-anagyrine (11). Their structures were elucidated by spectroscopic methods, and the stereochemistry of 8 was confirmed by X-ray analysis. These alkaloids were tested for anti-hepatitis B virus (HBV) activity in vitro, compounds 5, 6, 9, and 10 showed significant anti-HBV activity with inhibitory potency against HBsAg secretion at 48.3-79.3% and that against HBeAg secretion at 24.6-34.6%.     

Radiosynthesis of carbon-11-labeled camptothecin derivatives as potential positron emission tomography tracers for imaging of topoisomerase I in cancers

Four carbon-11-labeled camptothecin derivatives, 9-[11C]methoxy-20(S)-camptothecin ([11C]5), 10-[11C]methoxy-20(S)-camptothecin ([11C]7), 9-nitro-10-[11C]methoxy-20(S)-camptothecin ([11C]9), and 9-[([11C]trimethylamino)methyl]-10-hydroxy-20(S)-camptothecin ([11C]11), have been synthesized as potential positron emission tomography tracers for imaging of topoisomerase I in cancers.     

水朝阳旋覆花化学成分的研究

从水朝阳旋覆花(Inula helianthus-aquatica)地上部分分离得到24个化合物,经波谱数据分析分别鉴定为aromaticin(1),8-epi-helenalin(2),bigelovin(3),2,3-dihydroaromaticin(4),carpesiolin(5),ergolide(6),inuchinenolide C(7),6α-acetoxy-isoinuviscolide(8),8-epi-inuviscolide(9),inuchinenolide B(10),tomentosin(11),11α,13-dihydrotomentosin(12),inuchinenolide A(13),4H-tomentosin(14),11β,13-dihydro-4H-tomentosin(15),11-epi-sundiversifolide(16),sundiversifolide(17),8,9,10-三羟基百里香酚(18),10-羟基-8,9-双氧亚异丙基百里香酚(19),8,10-二羟基-9-异丁酰百里香酚(20),8-羟基-9,10-二异丁酰百里香酚(21),8-羟基-9-异丁酰-10-(2-甲基丁酰)百里香酚(22),8,9-环氧-9,10-二异丁酰百里香酚(23)和8,9-环氧-3-异丁酰-10-(2-甲基丁酰)百里香酚(24)。除了化合物1～6外,其他化合物均为首次从该植物中分离得到。     

Four steroidal alkaloids from the leaves of Buxus sempervirens

Four new steroidal alkaloids, N20-formylbuxaminol E [(20S)-16alpha-hydroxy-20-(formylamino)-3beta-(dimethylamino)-9,10 -seco-buxa-9(11),10(19)-diene] (1), O16-syringylbuxaminol E [(20S)-16alpha-syringoyl-3beta-(dimethylamino)-20-(amino)-9, 10-seco-buxa-9(11),10(19)-diene] (2), N20-acetylbuxamine G [(20S)-20-(acetylamino)-3beta-(methylamino)-9,10-seco-buxa-9(11),1 0(19)-diene] (3) and N20-acetylbuxamine E [(20S)-20-(acetylamino)-3beta-(dimethylamino)-9,10-seco-buxa-9(11) ,10(19)-diene] (4) were isolated from the leaves of Buxus sempervirens. Their structures were determined mainly on the basis of 2D NMR studies.     

Absolute configuration of labdanes and ent-clerodanes from Chromolaena pulchella by vibrational circular dichroism

The aerial parts of Chromolaena pulchella biosynthesize two groups of diterpenes belonging to opposite enantiomeric series, specifically, the furanoid ent-clerodanes (5R,8R,9S,10R)-(-)-hardwikiic acid (1), methyl (5R,8R,9S,10R)-(-)-hardwikiate (2), (5S,8R,9S,10R)-(-)-hautriwaic acid lactone (3), methyl (5R,8R,9S,10R)-(-)-nidoresedate (4) and methyl (8R,9R)-(-)-strictate (5), as well as the labdanes (5S,8R,9R,10S)-(+)-(13E)-labd-13-ene-8,15-diol (6) and (5S,8R,9R,10S)-(+)-isoabienol (7). The absolute configuration of the two groups of diterpenes was unambiguously assigned by comparison of the vibrational circular dichroism spectra of 3 for ent-clerodanes, and of 7 for labdanes with their theoretical spectra obtained by density functional theory calculations. The results support a biogenetic proposal to diterpenes found in the studied botanical species.     

The roles of turn formation and cross-strand interactions in fibrillization of peptides derived from the OspA single-layer beta-sheet

We previously demonstrated that a beta-hairpin peptide, termed BH(9-10), derived from a single-layer beta-sheet of Borrelia OspA protein, formed a native-like beta-turn in trifluoroethanol (TFE) solution, and it assembled into amyloid-like fibrils at higher TFE concentrations. This peptide is highly charged, and fibrillization of such a hydrophilic peptide is quite unusual. In this study, we designed a circularly permutated peptide of BH(9-10), termed BH(10-9). When folded into their respective beta-hairpin structures found in OspA, these peptides would have identical cross-strand interactions but different turns connecting the strands. NMR study revealed that BH(10-9) had little propensity to form a turn structure both in aqueous and TFE solutions. At higher TFE concentration, BH(10-9) precipitated with a concomitant alpha-to-beta conformational conversion, in a similar manner to the BH(9-10) fibrillization. However, the BH(10-9) precipitates were nonfibrillar aggregation. The precipitation kinetics of BH(10-9) was exponential, consistent with a first-order molecular assembly reaction, while the fibrillization of BH(9-10) showed sigmoidal kinetics, indicative of a two-step reaction consisting of nucleation and molecular assembly. The correlation between native-like turn formation and fibrillization of our peptide system strongly suggests that BH(9-10) adopts a native-like beta-hairpin conformation in the fibrils. Remarkably, seeding with the preformed BH(10-9) precipitates changed the two-step BH(9-10) fibrillization to a one-step molecular assembly reaction, and disrupted the BH(9-10) fibril structure, indicating interactions between the BH(10-9) aggregates and the BH(9-10) peptide. Our results suggest that, in these peptides, cross-strand interactions are the driving force for molecular assembly, and turn formation limits modes of peptide assembly.     

C(15) Acetogenins from the red alga Laurencia obtusa.

Four C(15) acetogenins, 13-epilaurencienyne (3Z) (1), 13-epipinnatifidenyne (3E) (2), (3E, 6S(*), 7R(*), 9S(*), 10S(*), 12R(*))-9-chloro-13-bromo-6:12-epoxy-7, 10-diacetoxypentadec-3-en-1-yne (3), (3Z, 6S(*), 7R(*), 9S(*), 10S(*), 12R(*))-9-chloro-13-bromo-6:12-epoxy-7, 10-diacetoxypentadec-3-en-1-yne (4), along with the known 13-epilaurencienyne (3E) (5), have been isolated from the organic extract of the red alga Laurencia obtusa, collected in the Aegean Sea, Greece. The structures of the new natural products, as well as their relative stereochemistry, were established by means of spectral data analysis, including 2D NMR spectroscopic experiments. Some of the new metabolites exhibited significant insecticidal activity.     

Peroxygenase-Catalyzed Fatty Acid Epoxidation in Cereal Seeds (Sequential Oxidation of Linoleic Acid into 9(S),12(S),13(S)-Trihydroxy-10(E)-Octadecenoic Acid)

Peroxygenase-catalyzed epoxidation of oleic acid in preparations of cereal seeds was investigated. The 105,000g particle fraction of oat (Avena sativa) seed homogenate showed high peroxygenase activity, i.e. 3034 [plus or minus] 288 and 2441 [plus or minus] 168 nmol (10 min)-1 mg-1 protein in two cultivars, whereas the corresponding fraction obtained from barley (Hordeum vulgare and Hordeum distichum), rye (Secale cereale), and wheat (Triticum aestivum) showed only weak activity, i.e. 13 to 138 nmol (10 min)-1 mg-1 protein. In subcellular fractions of oat seed homogenate, peroxygenase specific activity was highest in the 105,000g particle fraction, whereas lipoxygenase activity was more evenly distributed and highest in the 105,000g supernatant fraction. Incubation of [1-14C]linoleic acid with the 105,000g supernatant of oat seed homogenate led to the formation of several metabolites, i.e. in order of decreasing abundance, 9(S)-hydroxy-10(E),12(Z)-octadecadienoic acid, 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acid, cis-9,10-epoxy-12(Z)-octadecenoic acid [mainly the 9(R),10(S) enantiomer], cis-12,13-epoxy-9(Z)-octadecenoic acid [mainly the 12(R),13(S) enantiomer], threo-12,13-dihydroxy-9(Z)-octadecenoic acid, and 12(R),13(S)-epoxy-9(S)-hydroxy-10(E)-octadecenoic acid. Incubation of linoleic acid with the 105,000g particle fraction gave a similar, but not identical, pattern of metabolites. Conversion of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acid, a naturally occurring oxylipin with antifungal properties, took place by a pathway involving sequential catalysis by lipoxygenase, peroxygenase, and epoxide hydrolase.     

Taxanes with C-5-amino-side chains from the needles of Taxus canadensis

Five taxanes with an amino-side chain on C-5 were identified for the first time in the needles of the Canadian yew, Taxus canadensis. Their structures were characterized as 2alpha,7beta,9alpha,10beta,13-pentaacetoxy-11beta-hydroxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),12-diene (1), 2alpha,9alpha-dihydroxy-10beta,13alpha-diacetoxy-5alpha-(3'-methylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (2), 2alpha17-dihydroxy-9alpha,10beta,13alpha-triacetoxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (3), 2alpha-hydroxy-7beta,9alpha,10beta,13alpha-tetraacetoxy-5alpha-(2'-hydroxy-3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (4), and 9alpha-hydroxy-2alpha,10beta,13alpha-triacetoxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (5) on the basis of 1D-, 2D-NMR spectroscopic data and high-resolution fast atom bombardment MS analyses. Metabolite (1) was isolated from the needles of the Canadian yew for the first time but had previously been detected in the stems of the Japanese yew, whereas taxanes (2-5) are only now reported. Metabolite (3) is the first reported nitrogen-containing taxane with a 17-hydroxyl substitution.     

Mechanism of degradation of LH-RH and neurotensin by synaptosomal peptidases

The products of degradation of LH-RH and neurotensin by synaptosomes isolated from rat hypothalamus and cortex have been identified. LH-RH is cleaved at Tyr5-Gly6 and Pro9-Gly10 giving rise to LH-RH (1-5), LH-RH (6-10) and LH-RH (1-9). Neurotensin is cleaved at Arg8-Arg9, Pro10-Tyr11 and Ile12-Leu13, giving neurotensin (1-8), neurotensin (1-10), neurotensin (1-12) and neurotensin (9-13) as major products. While most of the peptidase activity is localized in the cytoplasmic fraction, a small but significant proportion is membrane bound. For LH-RH, the specificity of the membrane-bound activity is similar to that in the cytosol fraction; for neurotensin, the membrane fraction preferentially gives rise to the (1-10) and (1-11) peptides. The most potent inhibitors of the LH-RH and neurotensin degrading enzymes in synaptosomes are heavy metal ions (mercury and copper), p-chloromercuribenzoate and 1,10 phenanthroline.