Synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-3H8]-analogues through a common synthetic route

Total synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-³H₈]-analogues via the corresponding p-toluenesulphonates is reported. This synthetic approach allows the preparation of radioactively labelled arachidonic acid derivatives following a common synthetic route. Activity assays indicated that 15-lipoxygenases may tolerate the azido group in the substrate binding pocket and thus, radioactively labelled azido compounds may be used as photo-affinity probes to investigate mechanistic features of eicosanoid biosynthesis.     

Statistical analysis of in situ hybridization data: Derivation and use of the Zmax test

There are many situations in which grain distributions resulting from in situ hybridization of radioactively labeled probes to unique genes should be subjected to a statistical analysis. However, the problems posed by analysis of in situ hybridization data are not straightforward, and no completely satisfying method is currently available. We have developed a procedure in which the major and any number of minor site(s) of hybridization may be specifically located and the significance of each tested. This Z_max procedure first tests the overall distribution for departure from randomness and then identifies significantly overlabeled whole chromosomes (or chromosome arms or other large segments), a process that may be repeated to pinpoint significantly overlabeled regions within these chromosomes. We describe in detail the derivation of the Z_max statistic, present tables of significant Z_max levels, and show with examples how Z_max is used in tests of significance of in situ hybridization data.     

(Z)-3-nonenol, (Z,Z)-3,6-nonadienol and (S,S)-(-)-epianastrephin: male produced pheromones of the Mexican fruit fly

(Z)-3-nonenol, (Z,Z)-3,6-nonadienol and (S,S)-(-)-epianastrephin proved active as male-produced pheromones which elicited behavioral responses from virgin female Mexican fruit flies (Anastrepha ludens) (Diptera: Tephritidae) in laboratory bioassays. All three chemicals elicited attraction and/or locomotor arrest when tested individually. When tested together, (Z)-3-nonenol inhibited the behavioral effect of (Z,Z)-3,6-nonadienol but either of the alcohols synergized the effect of (S,S)-(-)-epianastrephin. Quantities of the pheromones per male abdomen were: (Z)-3-nonenol-100 ng; (Z,Z)-3,6-nonadienol-40 ng; and total epianastrephin (R,R and S,S enantiomers)-700 ng. Relative to the quantities in abdominal extract, males released these chemicals during sexual display in a blend containing a higher proportion of the alcohols.

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Résumé Le (Z)-3-nonènol, le (Z,Z)-3,6-nonadiènol et le (S,S)-(-)-épianastréphine produits par les mâles de la mouche mexicaine du fruit (Anastrepha ludens) (Diptera: Tephritidae) ont attirés les femelles lors de tests conduits en laboratoire. Le pouvoir attractif du (Z)-3-nonènol est faible comparé à celui des deux autres phéromones. Evalués ensemble, le (Z)-3-nonènol inhibe l'attractivité du (Z,Z)-3,6-nonadiènol mais chacun des deux alcools synergise l'effet attractif de la (S,S)-(-)-épianastréphine. Les quantités recouvrées par mâle dans un extrait abdominal étaient respectivement de 100, 40 et 700 ng pour le (Z)-3-nonènol, le (Z,Z)-3,6-nonadiènol, et l'épianastréphine totale (R,R et S,S) énantiomères. Comparées à ces valeurs, le mélange élange émis par les mâles lors de leur cour sexuelle est plus riche in alcools. Le rapport (Z)-3-nonènol (Z,Z)-3,6-nonadiènol est cependant identique dans l'extrait abdominal et dans le mélange émis par les mâles.

     

Concise Synthesis of (8Z,11Z,14Z)-8,11,14-Heptadecatrienal, (7Z,10Z,13Z)-7,10,13-Hexadecatrienal,and (8Z,11Z)-8,11-Heptadecadienal,Components of the Essential Oil of Marine Green Alga Ulva pertusa

The long-chain aldehydes, (8Z,11Z,14Z)-8,11,14-heptadecatrienal, (7Z,10Z,13Z)-7,10,13-hexadecatrienal, and (8Z,11Z)-8,11-heptadecadienal, were concisely synthesized by using Grignard coupling, catalytic hydrogenation with the Lindlar catalyst, and oxidation with Dess–Martin periodinane as the key steps. Particularly, (8Z,11Z,14Z)-8,11,14-heptadecatrienal and (7Z,10Z,13Z)-7,10,13-hexadecatrienal both possessed a seaweed-like odor.     

E versus Z geometry in β-d-arabino-hexopyranosidulose oximes

Koenigs–Knorr-type glycosidations of peracylated 2Z-benzoyloxyimino-glycopyranosyl bromides invariably proceed with retention of the Z-geometry. Accordingly, the many β-d-hexosidulose oximes in literature which were prepared in this way and for which the oxime geometry has not been addressed explicitly, are the Z-oximes throughout. By contrast, oximation of β-d-hexopyranosid-2-uloses leads to mixtures of E and Z oximes readily separable and structurally verifiable by ¹H and ¹³C NMR. Configurational assignments rested on comparative evaluation of NMR data of E and Z isomers, and, most notably on an X-ray structural analysis of the pivaloylated isopropyl 2E-benzoyloxyimino-2-deoxy-β-d-arabino-hexopyranoside revealing the unusual ¹S₅^1,4B conformation for the pyranoid ring.     

Ferulic acid dehydrodimers from wheat bran: isolation,purification and antioxidant properties of 8-0-4-diferulic acid

Summary

Wheat bran contains several ester-linked dehydrodimers of ferulic acid, which were detected and quantified after sequential alkaline hydrolysis. The major dimers released were: trans-5-[(E)-2-carboxyvinyl]-2-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid (5–8-BendiFA), (Z)-β-(4-[(E)-2-carboxyvinyl]-2-methoxy-phenoxy)-4-hydroxy-3-methoxycinnamic acid (8-O-4-diFA) and (E,E)-4,4′-dihydroxy-5,5′-dimethoxy-3,3′-bicinnamic acid (5–5-diFA). trans-7-hydroxy-1-(4-hydroxy-3methoxyphenyl)-6-methoxy-1,2-dihydro-naphthalene-2,3-dicarboxylic acid (8–8-diFA cyclic form) and 4,4′-dihydroxy-3,3′-dimethoxy-β,β'-bicinnamic acid (8–8-diFA non cyclic form) were not detected. One of the most abundant dimers, 8-O-4-diFA, was purified from de-starched wheat bran after alkaline hydrolysis and preparative HPLC. The resultant product was identical to the chemically synthesised 8-O-4-dimer by TLC and HPLC as confirmed by ¹H-NMR and mass spectrometry. The absorption maxima and absorption coefficients for the synthetic compound in ethanol were: λ_max: 323 nm, λ_min: 258 nm, ε_λmax (M^?1cm^?1): 24800 ± 2100 and ε₂₈₀ (M^?1cm^?1): 19700 ± 1100. The antioxidant properties of 8-O-4-diFA were assessed using: (a) inhibition of ascorbate/iron-induced peroxidation of phosphatidylcholine liposomes and; (b) scavenging of the radical cation of 2,2′-azinobis (3-ethyl-benzothiazoline-6-sulphonate) (ABTS) relative to the water-soluble vitamin E analogue, Trolox C. The 8-O-4-diFA was a better antioxidant than ferulic acid in both lipid and aqueous phases. This is the first report of the antioxidant activity of a natural diferulate obtained from a plant.     

Assessing the absolute configuration of (7S,8R)-(−)-epoxyjasmone

The absolute configuration of cis-epoxyjasmone (−)-2, isolated from Trichosporum cutaneum CCT 1903 whole cells, has been unambiguously established as (7S,8R), [α]_D²⁰ −29.0° (c 1.3, CHCl₃), by a new two step method, using a regioselective epoxide opening as the key step followed by Mosher acid derivatization.     

Crystal Structure and Conformation of 8-(2-Hydroxyethylamino) and 8-(Pyrrolidin-1-yl) Adenosines

In the course of investigation of 8-alkylamino substituted adenosines, the title compounds were synthesized as potential partial agonists for adenosine receptors. The structure determination of these compounds was carried out with the X-ray crystallography study. Crystals of 8-(2-hydroxyethylamino)adenosine are monoclinic, space group P 2₁; a = 7.0422(2), b = 11.2635(3), c = 8.9215(2) Å, β = 92.261(1)°, V = 707.10(3) ų, Z = 2; R-factor is 0.0339. The nucleoside is characterized by the anti conformation; the ribose ring has the C(2′)-endo conformation and gauche–gauche form across C(4′)–C(5′) bond. The molecular structure is stabilized by intramolecular hydrogen bond of N–H·O type. Crystals of 8-(pyrrolidin-1-yl)adenosine are monoclinic, space group C 2; a = 19.271(1), b = 7.3572(4), c = 11.0465(7) Å, β = 103.254(2)°, V = 1524.4(2) ų, Z = 4; R-factor is 0.0498. In this compound, there is syn conformation of the nucleoside; the ribose has the C(2′)-endo conformation and gauche–gauche form across C(4′)–C(5′) bond. The molecular structure is stabilized by intramolecular hydrogen bond of O–H·N type. For both compounds, the branching net of intermolecular hydrogen bonds occur in the crystal structures.     

1-(2-((Z)-6-(2-(Trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)phenyl)piperidin-2-one as a new potent apoptosis agent

Compounds 4a–f, 5a–f and 6–9, showed significant growth inhibition activity against human tumor cell lines. Of these compounds, 1-(2-((Z)-6-(2-(trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)phenyl)piperidin-2-one (8) displayed the most potent growth inhibition activity. Compound 8 also arrested cancer cells in G2/M phase and induced apoptosis via activation of caspase-3 and -9. According to western-blotting analysis, compound 8 can up-regulate Bax, down-regulate Bcl-2 and XIAP, as well as promote cytochrome c release.     

Phthalide mono- and dimers from the radix of Angelica sinensis

Phytochemical investigation of the radix of Angelica sinensis has led to the isolation and identification of a new phthalide dimer, (3Z)-(3aR,6S,3′R,8′S)-3a.8′,6.3′-diligustilide (1), along with three known phthalide dimers, including riligustilide (2), levistolide A (3), senkyunolide O (4), and three known phthalide monomers, including 3,9-dihydroxyl-ligustilide (5), (Z)-butylidene phthalide (6), (Z)-ligustilide (7). Their structures were determined by spectroscopic methods including IR, NMR (¹H NMR, ¹³C NMR, COSY, HSQC, HMBC and NOESY) and MS. Meanwhile, the possible biosynthesis pathways of compounds 1 and 5 were hypothesized.     

Mating suppression in tethered females of Eupoecilia ambiguella by evaporation of (Z)-9-dodecenyl acetate in the field

(Z)-9-dodecenyl acetate, the major sex pheromone component of the European grape berry moth, Eupoecilia ambiguella, was continuously evaporated from 110 sources in a 20×20 m plot in a vineyard. inhibition of mating was demonstrated by releasing laboratory-reared males and exposing tethered females.At an average evaporation rate of 700 mg (Z)-9-dodecenyl acetate per day and hectare only 2 of 94 females were mated, at 200 mg per day and hectare 3 of 63 females, whereas 32 of 62 females were mated during the control period.

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Zusammenfassung Die Hauptkomponente des Sexualpheromons des Einbindigen Traubenwicklers, (Z)-9-Dodecenylacetat, wurde innerhalb einer Rebanlage in einer Parzelle von 20×20 m von 110 Punkten aus gleichmässig verdampft. Jeden Abend wurden in der Parzelle zwischen 100 und 200 männliche Falter aus einer Laborzucht freigelassen und 10 Weibchen ausgesetzt, die an kurzen Fäden befestigt waren.Bei einer Verdampfungsrate von 700 mg pro Tag und Hektar legten anschliessend nur 2 von 94 Weibchen fertile Eier, bei 200 mg pro Tag und Hektar 3 von 63, während in der Kontrollperiode dieses Verhältnis 32:62 betrug. Dies zeigt, dass der Traubenwickler durch die Desorientierung mit Sexuallockstoff an der Kopulation weitgehend gehindert werden kann.

     

Preparation, spectroscopic properties, crystal and molecular structure of pentacarbonyl(3-methyl-1-(pyridin-2-yl)-1,2,4-triazole-N)tungsten(0)

The synthesis and molecular structure of pentacarbonyl(3-methyl-l-(pyridin-2-yl)-l,2,4-triazole-N⁴)tungsten(0) are described. Surprisingly the ligand is bound to the W(CO)₅ moiety via the triazole N⁴ (N24) atom, and the pyridine to triazole link is between the pyridine C² (Cl) atom and the N¹ (N21) atom of the triazole ring. The compound crystallises in the space group C2/c with a=24.559(18), b=9.693(16), c=13.817(12) Å, β=108.48(12)° and Z=8. A full matrix least-squares refinement resulted in a final R=0.052 (R_w=0.065) for 3688 unique reflections.     

Dienic analogs of (Z)-5-decenyl acetate, a pheromone component of the turnip moth, Agrotis segetum: Synthesis, conformational analysis and structure-activity relationships

Structure-activity relationships for (Z, E)-dienic analogs of (Z)-5-decenyl acetate, a pheromone component of the turnip moth, Agrotis segetum, have been studied by electrophysiological single-cell recordings and molecular mechanics calculations. The biological activities of the dienic analogs are highly sensitive to the position of the additional (E) double bond. The experimental observations are well rationalized by the use of a receptor-interaction model in which the biological activity is determined by conformational energies required to mimic spatial relationships in the natural pheromone component. A biologically active conformation for this compound is suggested.     

The snake thyroid gland V. effects of hypophysectomy on iodine metabolism in the striped racer,Elaphe taeniura

Summary Thyroidal iodine metabolism in the hypophysectomized snake,Elaphe taeniura, was examined in vivo and in vitro using¹²⁵I. Hypophysectomy decreased, and TSH increased, both in vivo and in vitro thyroidal accumulation and uptake of radioiodine, and the amount of all labelled substances in the thyroid gland. The operation also altered the distribution of the relative amounts of labelled iodoamino acids in vivo, but not in vitro; nor was there any effect on release of these labelled substances in vitro. In view of the paucity of information available on poikilothermic species, the data are discussed in relation to those of hypothysectomized rats.Abbreviations DIT diiodotyrosine - KRPG Krebs-Ringer-phosphate solution, containing glucose - MIT monoiodotyrosine - PTU propylthiouracil - T ₄ thyroxine - TSH thyroid stimulating hormone     

Minor alkamides from Heliopsis longipes S.F. Blake (Asteraceae) fresh roots

From the fresh roots of Heliopsis longipes three new minor alkamides: longipinamide A (N-isobutyl-8,10-diynoic-3Z-undecenamide), longipenamide A (N-isobutyl-syn-8,9-dihydroxy-2E,6Z-decadienamide) and longipenamide B (N-isobutyl-syn-6,9-dihydroxy-2E,7E-decadienamide); three known alkamides: affinin (spilanthol, N-isobutyl-2E,6Z,8E-decatrienamide), N-isobutyl-2E,6Z-decadienamide and N-isobutyl-2E-decenamide; and 11 other known compounds were isolated. The structures of the three new minor alkamides were established by 1D and 2D NMR spectroscopy including ¹H, ¹³C, DEPT, COSY, HSQC, and HMBC experiments, as well as by EI and FAB⁺ mass spectrometry. To our knowledge, this is the first report of the isolation of linear dihydroxyalkamides as natural products.     

Synthesis of (S)-13-Hydroxy (2E,4E,8E)- and (2E,4E,8Z)-Tetradecatrienoic Acids

The syntheses of (S)-13-hydroxy-(2E,4E,8E)-tetradecatrienoic acid (1) and (2E,4E,8Z)-tetradecatrienoic acid (2) were carried out by using the Wittig reaction as the key step. The asymmetric center at C-13 and the double bond between C-8 and C-9 for natural compound 1 were reconfirmed as being of (S) configuration and E, respectively.

The relationship between the structure of the unsaturated hydroxy fatty acids and their inhibitory effect on the growth of lettuce was investigated.     

Synthesis of (3E, 5Z)-3,5-Dodecadienylacetate,the Sex Pheromone of Phtheochroa cranaodes (Lepidoptera: Tortricidae)

(3E, 5Z)-3,5-Dodecadienyl acetate, the female sex pheromone of Phtheochroa cranaodes, was regio and stereo-selectively synthesized from 1-octyne and (E)-4-bromo-3-buten-1-ol by using Pd(PPh₃)₄, CuI and piperidine to afford the enyne (5). Further elaboration afforded the target pheromone. The synthetic pheromone was identified with the natural product by its MS and IR, data GLC retention time and biological activity.     

Inhibition of gibberellin biosynthesis by paclobutrazol in cell-free homogenates ofCucurbita maxima endosperm andMalus pumila embryos

The plant growth retardant paclobutrazol, (PP333) (2RS, 3RS)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)pentan-3-ol, inhibits specifically the three steps in the oxidation of the gibberellin-precursorent-kaurene toent-kaurenoic acid in a cell-free system fromCucurbita maxima endosperm. The KI₅₀ for this inhibition is 2×10^–8 M. The KI₅₀ values for the separated2S, 3S, and2R, 3R enantiomers of paclobutrazol in this system are 2×10^–8 M and 7×10^–7 M, respectively. A cell-free preparation from immatureMalus pumila embryos convertsent-kaurene to gibberellin A₉, whereas no conversion occurs in a similar preparation fromMalus endosperm. The conversion ofent-kaurene by the embryo preparation is inhibited by paclobutrazol with KI₅₀ values for the2S,3S and2R,3R enantiomers of 2×10^–8 M and 6×10^–8 M, respectively.     

Structural comparison of (pentamethylcyclopentadienyl)iridium(III) azido complexes containing potentially N,S-bidentate N-heterocyclic thiolates: 2- or 8-quinolinethiolate and benzimidazole-2-thiolate

The crystal structures of mononuclear (azido)(pentamethylcyclopentadienyl)iridium(III) complexes bearing 2- or 8-quinolinethiolate (n-Sqn⁻), [Cp^∗Ir(N₃)(n-Sqn)] {n = 2 (1) or 8 (2); Cp^∗ = η⁵-C₅Me₅} have been determined by X-ray analysis. The 2-Sqn complex, 1, acquires severe steric strains in the four-membered κ²N,S chelate ring, while the 8-Sqn isomer, 2, forms a strain-free five-membered planar κ²N,S chelate ring. It has also been revealed that the corresponding benzimidazole-2-thiolate (Hbimt⁻) complex, which was obtained similarly to the above n-Sqn complexes from [Cp^∗Ir(N₃)₂]₂ and Na(Hbimt), takes an unsymmetrical dinuclear structure bridged by two Hbimt⁻ ligands with different bonding modes, [Cp^∗Ir(N₃){μ(S:N¹)-Hbimt}{μ(S:S)-Hbimt}Ir(N₃)Cp^∗] · MeOH (3).     

N7 and C8 coordinated purine complexes of [(NH3)5Os]. Crystal structures of 7-[9MeHyp(NH3)5Os]Cl3·H2O and 8-[1,3,7Me3Xan(NH3)5Os]Cl3·2H2O

Pentaammineosmium(III) coordinates to both the N7 and C8 positions of purine rings. The compound 7-[9MeHyp(NH₃)₅Os]Cl₃·H₂O crystallizes in the orthorhombic space group Pnma (No. 62) with the unit cell parameters: a=11.542(2), b=6.9841(8), c=21.960(3) Å and Z=4. The compound 8-[1,3,7Me₃Xan(NH₃)₅Os]Cl₃·2H₂O crystallizes in the monoclinic space group P2₁/c (No. 14) with the unit cell parameters: a=7.1228(X), b=14.613(1), c=19.667(1) Å, β=91.782(9)° and Z=4. The Os---C bond in the latter structure is 2.039(9) Å and the imidazolylidine ligand exerts a slight trans influence seen in the lengthening of the Os---N_ax distance (2.172(8) Å) by about 0.05 Å relative to the average of the equatorial Os---N_eq value of 2.123(8) Å. The spectroscopic, electrochemical and structural properties of these and additional N-bound purine complexes are compared with those of similar N7 and C8 ruthenium(III) species.