Synthesis of l-(4-2H)erythrose,l-)1-13C, 5-2H)arabinose and l-(2-13C, 5-2H)arabinose and identification of the intermediates by 2H and 13C-N.M.R. spectroscopy

l-(1-¹³C, 5-²H)Arabinose (6D) and l-(2-¹³C, 5-²H)arabinose (8D) have been synthesized by degradation of 2,3-O-isopropylidene-α-l-rhamnofuranose (2) to l-(4-²H)erythrose (5β,5αD), with subsequent chain elongation to 6D plus l-(1-¹³C, 5-²H)ribose (7D), the latter being converted into 8D. Intermediates were identified by complete assignment of the ¹³C chemical shifts employing carbon-carbon and carbon-deuterium coupling constants, deuteration shifts, differential isotope-shifts, and deuterium spectra. The anomeric carbon atoms of 2 and 2,3-O-isopropylidene-l-(1-²H) erythrose (4D) gave only single ¹³C resonances, suggesting that these two compounds exists in only one major anomeric configuration, clarifying previously reported work. The synthesis of 2,3-O-isopropylidene-l-(1-²H)rhmanitol (3D) facilitated the assignment of the signals in the ¹³C spectra of the nondeuterated analog. Specific deuterium-enrichment and the observed carbon-deuterium coupling (¹J_C,D ∼22 Hz) not only served to identify the deuterated carbon atom unambiguously in 3 but also permitted assignment of closely spaced resonances. The deuterium spectrum of 2,3-O-isopropylidene-l-(1-²H)erythrofuranose (4D) showed only a single resonance, indicating preponderance of one anomer, in accord with the observation of a single C-1 resonance in the ¹³C spectrum.     

Incorporation of 3H from delta-(L-alpha-amino (4,5-3H)adipyl)-L-cysteinyl-D-(4,4-3H)valine into isopenicillin N.

1. delta-(L-alpha-Amino[4,5-3H]adipyl)-L-cysteinyl-D-[4,4-3H]valine has been synthesized from its constituent amino acids, the L-alpha-amino[4,5-3H]adipic acid being obtained by reduction with 3H2 of methyl 5-acetamido-5,5-diethoxycarbonylpent-2-enoate and subsequent decarboxylation and hydrolysis. 2. In a cell-free system prepared by lysis of protoplasts of Cephalosporium acremonium 3H was incorporated from the doubly labelled tripeptide into a compound that behaved like penicillin N or isopenicillin N. The relative specific radioactivities of the alpha-aminoadipyl and penicillamine moieties of the penicillin were the same (within experimental error) as those of the alpha-aminoadipic acid and valine residues respectively of the tripeptide. 3. The behaviour of the labelled alpha-aminoadipic acid from the penicillin to the L-amino acid oxidase of Crotalus adamanteus venom showed that it was mainly L-alpha-aminoadipic acid. 4. The results are consistent with the hypothesis that the carbon skeleton of the LLD-tripeptide is incorporated intact into the penicillin molecule and that the first product is isopenicillin N.     

Design, synthesis and anticonvulsant activities of novel 1-(substituted/unsubstituted benzylidene)-4-(4-(6,8-dibromo-2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl)phenyl) semicarbazide derivatives

Novel quinazolinone derivatives 5a-5n were designed, synthesized and screened for antiepileptic activity using MES and scPTZ seizures tests. Neurotoxicity study was performed by rotorod test. Compounds 5c, 5d, 5g, 5j and 5k were found active in the preliminary screening in MES model and/or scPTZ model. Further all these five compounds were administered to rats, 5c and 5d showed better activity than Phenytoin in oral route. Among all the title compounds tested, the most active one was 5c that revealed protection in MES at a dose of 30 mg/kg (ip) after 0.5 and 4h. This molecule also provided protection in the scPTZ at a dose of 100mg/kg (0.5h) and 300 mg/kg (4h).     

The role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle regeneration. Studies in TNF-alpha(-/-) and TNF-alpha(-/-)/LT-alpha(-/-) mice.

The role of tumor necrosis factor-alpha (TNF-alpha), an important mediator of the inflammatory response after injury, was investigated in regenerating skeletal muscle. The pattern of expression of TNF-alpha during muscle regeneration was examined by immunohistochemistry in tissue sections of crush-injured or transplanted muscle autografts and in primary cultures of adult skeletal muscle. TNF-alpha was highly expressed in injured myofibers, inflammatory cells, endothelial cells, fibroblasts, and mast cells. Myoblasts and myotubes also expressed TNF-alpha in primary muscle cultures and tissue sections. The essential role of TNF-alpha and its homologue lymphotoxin-alpha (LT-alpha) during muscle regeneration was assessed by basic histology in TNF-alpha(-/-) and TNF-alpha(-/-)/LT-alpha(-/-) mice. No difference was apparent in the onset or pattern of muscle regeneration (i.e., inflammatory response, activation and fusion of myoblasts) between the two strains of null mice or between nulls and normal control mice. However, both strains of null mice appeared more prone to bystander damage of host muscle and regeneration distant from the site of injury/transplantation. Although expression of TNF-alpha may play an important role in muscle regeneration, the studies in the null mice show that redundancy within the cytokine system (or some other response) can effectively compensate for the absence of TNF-alpha in vivo.     

3-(4-Methyl-3-pentenyl)-2(5H)-furanone, alpha,alpha-acariolide and 4-(4-methyl-3-pentenyl)-2(5H)-furanone, alpha,beta-acariolide: new monoterpene lactones from the astigmatid mites, Schwiebea araujoae and Rhizoglyphus sp. (Astigmata: Acaridae)

A new monoterpene lactone from the acarid mite, Schwiebea araujoae, was elucidated without its isolation by GC/FT-IR and GC/MS analyses to be 3-(4-methyl-3-pentenyl)-2(5H)-furanone (1) and tentatively named as alpha,alpha-acariolide. The structure of 1 was identified by its synthesis from alpha-bromo-gamma-butyrolactone via 4 reaction steps. The synthesized compound gave the same GC/MS and GC/FT-IR spectra as those of the natural product. The other monoterpene lactone was likewise elucidated from the unidentified Rhizoglyphus mite to be 4-(4-methyl-3-pentenyl)-2(5H)-furanone (2) and named as alpha,beta-acariolide; it was also identified by its synthesis in 5 reaction steps from the same butyrolactone as the starting material. GC/MS and GC/FT-IR spectra of the preparation were identical to those of the natural product.     

Ternary Cu(II) complexes, Cu(H(-1)L)(ACys-) and Cu(H(-2)L)(ACys-); L = peptides, ACys- = N-acetyl-cysteinate. Analogous complexes to the intermediates in the transport of Cu(II) from Cu(H(-2)L) to cysteine

The Cu(II) in Cu(H(-2)L) has been postulated to be successively transported to cysteine (Cys) as follows; Cu(H(-2)L) <==> Cu(H(-2)L)(Cys*-) <==> Cu(H(-1)L)(Cys*-) --> Cu(H(-1)L)(Cys-), where Cys*- denotes the monodentate Cys-. N-acetyl-cysteinate (ACys-) complexes Cu(H(-2)L)(ACys-) and Cu(H(-1)L)(ACys-), having similar coordination modes to Cu(H(-2)L)(Cys*-) and Cu(H(-1)L)(Cys*-), respectively, exhibited the S --> Cu(II) charge transfer absorption at 325-355 nm and the d-d absorption at 530-610 nm. A linear interrelation existed between the energies of the CD and d-d absorptions. Cu(H(-2)L)(ACys-) were in rapid equilibrium with Cu(H(-1)L)(ACys-). Upon forming the ternary complex, pK(c2) of the parent Cu(H(-1)L) was raised to more than 1.0. The formation constants (K) of the Cu(H(-1)L)(ACys-) species from Cu(H(-1)L) were bigger than those of Cu(H(-2)L)(ACys-) from Cu(H(-2)L). The linear free-energy relationship existed between the free-energy change (deltaG) and the entropy change (deltaS) for the ternary complex formation. The rate constants (k1+) for the Cu(H(-1)L)(Cys-) formation closely correlated with the K values for Cu(H(-2)L)(ACys-). The ternary complexes containing ACys are considered to be analogous complexes to the intermediates in the transport of Cu(II) from peptides to cysteine.     

四川重楼属（延龄草科）一新变种——短瓣凌云重楼

描述了四川延龄草科重楼属一新变种——短瓣凌云重楼[Paris cronquistii (Takht.)H.Li var.brevipetalata H.X.Yin et H.Zhang].新变种——短瓣凌云重楼与凌云重楼[P.cronquistii (Takht.)H.Li]相似,区别在于花瓣线形、长1.2～3.1 cm、远短于萼片、下垂,雄蕊较少、8～12枚,仅2轮,叶上表面深绿色,沿中脉具淡绿色斑纹.     

(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.

     

Synthesis, antibacterial activity, and quantitative structure-activity relationships of new (Z)-2-(nitroimidazolylmethylene)-3(2H)-benzofuranone derivatives

A new series of (Z)-2-(1-methyl-5-nitroimidazole-2-ylmethylene)-3(2H)-benzofuranones (11a-p) and (Z)-2-(1-methyl-4-nitroimidazole-5-ylmethylene)-3(2H)-benzofuranones (12a-m) were synthesized and assayed for their antibacterial activity against Gram-positive and Gram-negative bacteria. Most of the 5-nitroimidazole analogues (11a-p) showed a remarkable inhibition of a wide spectrum of Gram-positive bacteria (Staphylococcus aureus, Streptococcus epidermidis, MRSA, and Bacillus subtilis) and Gram-negative Klebsiella pneumoniae, whereas 4-nitroimidazole analogues (12a-m) were not effective against selected bacteria. The quantitative structure-activity relationship investigations were applied to find out the correlation between the experimentally evaluated activities with various parameters of the compounds studied. The QSAR models built in this work had reasonable predictive power and could be explained by the observed trends in activities.