bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of dihydrolysergol analogues
Authors: Mantegani Sergio , Traquandi Gabriella , Varasi Mario
Published: March 2009

As a part of a search for novel biological active ergoline derivatives, the indole ring present in the ergoline skeleton (indole[4,3‐f,g]quinoline) was converted into different heterocyclic ring systems such as quinazoline 2, benzofurane 3 and benzoxazole 4. Due to the paramount importance of chirality to attain biological activity, natural dihydrolysergic acid 1 was chosen as starting material and a synthetic pathway conservative in term of chirality was followed.
The synthesis and transformations of 2‐[2‐ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl]amino‐3‐dimethylaminopropenoates. the synthesis of substituted β‐amino‐α,β‐didehydro‐a‐amino acid derivatives
Authors: Jukić Lucija , Rečnik Simon , Svete Jurij , Stanovnik Branko , Grdadolnik Simona GoliČ
Published: March 2009

Alkyl (Z)‐2‐[(E)‐2‐ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl]amino‐3‐dimethylaminopropenoates 7 and 8 were prepared from ethyl 2‐pyridinylacetate (1) in two steps. Substitution of the dimethylamino group with alkyl‐, aryl‐, or heteroarylamines afforded the corresponding β‐alkyl‐ 22–24, β‐aryl‐ 25–35, and β‐herteroaryl‐amino‐α,β‐didehydro‐α‐amino acid 36 and 37 derivatives, intermediates for further preparation of various heterocyclic systems. The orientation around both double bonds were determined by various nmr techniques.
1H‐4,5,6,7‐Tetrahydro‐1,3‐diazepines. part II: basicity and hydrolysis of 1, 2‐diaryl derivatives
Authors: Hedrera Mónica E. , Perillo Isabel A. , Fernández Beatriz
Published: March 2009

Basicity and alkaline hydrolysis of 1,2‐diaryl‐1H‐4,5,6,7‐tetrahydro‐1,3‐diazepines 1 are studied. Results are analyzed on the basis of Hammett and Swain‐Lupton constants, finding good structure‐basicity correlation when both, inductive and mesomeric effects, are considered together. Regioselectivity is observed in the alkaline hydrolysis of compounds 1, and it is analyzed in light of the stereoelectronic control theory. Results are compared with those previously obtained for five and six membered ring homologues: 1H‐4, 5‐dihydroimidazoles and 1,4,5,6‐tetrahydropyirimidines respectively.
Synthesis of bis‐heteroaryl piperazine derivatives as potential reverse transcriptase inhibitors
Authors: Guillaumel Jean , Grierson David S. , Monneret Claude
Published: March 2009

Vinylogous analogs of non‐nucleoside reverse transcriptase inhibitors belonging to the bis‐(hetero‐aryl)piperazine (BHAP) series were synthesized by coupling a piperazine derivative with (E)‐propenoyl derivatives of heterocyclic moieties.
Reactions of cyclic oxalyl compounds, 43: Synthesis and thermolysis of fused 1‐arylaminopyrrolones
Authors: Kollenz Gert , Theuer Ralph , Peters Karl , Peters Eva‐Maria
Published: March 2009

Fused N‐(di)arylamino‐pyrrol‐2,3‐diones 1 are reacted with diphenylketene, thiosemicarbazide or 1,2‐diaminobenzene to afford the 3‐diphenylmethylene pyrrolones 2, the thiosemicarbazones 4 or the quinoxaline derivatives 5 as well as 6, respectively. Thermolysis of 2b,c,e,f,6b and the pyrrolo‐quinoxaline 8 afford the corresponding N‐deaminated products 3, 7 and 9. Rearrangements into diazapropellanes following a thermally initiated Fischer ‐ indolization as originally expected do not occur.
Reactions of 3‐substituted chromones with ortho‐phenylenediamine
Authors: Risitano Francesco , Grassi Giovanni , Foti Francesco
Published: March 2009

Chromones 1 react with diamine 2 to give various products depending on the nature of the position 3 substituent in the heterocycle.
Synthesis of η6‐(4a‐Methyl‐1,2,3,4‐tetrahydro‐4aH‐carbazole)‐tricarbonylchromium complex and stereoelectronic behaviour with organolithium reagents: an apparent frontal attack to the (CO)3Cr group
Authors: Rodríguez J. Gonzalo , Urrutia Anahí , Lafuente Antonio
Published: March 2009

The synthesis of η6‐(4a‐methyl‐1,2,3,4‐tetrahydro‐4aH‐carbazole)tricarbonylchromium (3) is described, and its reactivity with organolithium reagents have been analysed. The addition of RLi (R= H, Me, n‐Bu, tert‐Bu) to 3 affords the corresponding endo/exo tricarbonylchromium complexes of cis‐4a‐methyl‐9a‐substituted‐1,2,3,4‐tetrahydro‐4aH‐carbazole, which permit the consideration of the stereoelectronic behaviour of the tricarbonylchromium group on 4a‐methyl and the 9a substituent or on the methylenes of the cyclohexene moiety in the complexes.
An inexpensive, selective procedure for oxidizing α‐methyl to α‐formyl pyrroles pavel bobal
Authors: Lightner David A.
Published: March 2009

α‐Methylpyrroles are converted to α‐formyl by sodium bromate in aqueous methanol in ∼60% yield. Adding 1% ceric ammonium nitrate as a co‐oxidant brings the isolated yields of synthetically useful 2‐formylpyrroles 2a‐d up to ∼70%, or close to those found when using only the considerably more expensive ceric ammonium nitrate as oxidant.
Ruthenium‐catalyzed synthesis of quinolines via reductive heteroannulation of nitroarenes with 3‐amino‐1‐propanols
Authors: Cho Chan Sik , Kim Tae Kyung , Kim Tae‐Jeong , Shim Sang Chul , Yoon Nam Sik
Published: March 2009

Nitroarenes are reductively cyclized with 3‐amino‐1‐propanols in dioxane/H2O in the presence of a ruthenium catalyst and tin(II) chloride dihydrate together with isopropanol to afford the corresponding quinolines. A reaction pathway involving initial reduction of nitroarenes to anilines, propanol group transfer from 3‐amino‐1‐propanols to anilines, N‐alkylation of anilines by 3‐anilino‐1‐propanols and heteroannulation of 1,3‐dianilinopropanes is proposed.
Novel synthesis of 3‐phenylazo‐1,5‐benzothiazepines, ‐1,5‐benzoxazepines and ‐1,5‐benzodiazepines via a one‐pot reaction
Authors: Abd El Latif Fawi M. , El‐Rady Eman A. , Khalil Mohamed A. , El‐Maghraby M. A.
Published: March 2009

Novel polysubstituted ‐1,5‐benzothiazepine, ‐1,5‐benzoxazepine, and ‐1,5‐benzodiazepine were prepared in good yields by the reaction of hydrazono derivatives with o‐thioaminophenol, o‐aminophenol and o‐phenylenediamine via a one‐pot reaction.
Diastereoselective access to chiral non‐racemic [1,3]oxazolo‐[2,3‐a]isoindol‐5‐one ring systems viaO‐cationic cyclization
Authors: Sikoraiová Jana , Marchalín ŠTefan , Chihab‐Eddine Abderrahim , Daïch Adam
Published: March 2009

Dedicated to Professor Jean Morel for his retirement

The title compounds 4 have been prepared from suitable β‐amino‐ alcohol 2 and phthalic anhydride (5) in a three‐step sequence in moderate to good yields (58‐94%). The key step of this methodology is based on an intramolecular O‐cationic cyclization involving N‐acyliminium species. The high levels of the observed chemoselectivity during the intermolecular or intramolecular cyclization were also discussed.
Tin(II) chloride‐mediated synthesis of 2‐substituted benzoxazoles
Authors: Cho Chan Sik , Kim Dong Tak , Zhang Jiao Qiang , Ho Son‐Lam , Kim Tae‐Jeong , Shim Sang Chul
Published: March 2009

2‐Aminophenols react with an array of carboxylic acids in dioxane at 180° in the presence of tin(II) chloride to afford the corresponding 2‐substituted benzoxazoles in good yields. The reaction is applicable to a wide range of alkyl, alkenyl, aryl carboxylic acids.
Versatility of the pyridazine system: Chemistry and biology
Authors: Cignarella G. , Barlocco D.
Published: March 2009

In accordance with the title of my lecture, I am going to briefly illustrate our researches on pyridazine derivatives active in different biological areas.
Synthesis and biological activities of quinolone analogues: Pyridazino[3,4‐b]quinoxalin‐4‐one
Authors: Kurasawa Yoshihisa , Kim Ho Sik
Published: March 2009

Quinolone analogues I‐VI with pyridazino[3,4‐b]quinoxaline ring system were synthesized form the (l‐alkylhydrzino)quinoxalina N‐oxides 1 via oxidation of pyridazino[3,4‐b]quinoxalines 2,3,5,7, quinoxalino[2,3‐c]cinnolines 4, and 1,2‐dizepino[3,4‐b]quinoxalines 6. The biological activities of quinolone analogues IVa (N1‐methyl‐C3‐methyl), Va (N1‐methyl‐C3‐ethyl), and VI (N1‐methyl‐C3‐H) were superior to those of quinolone analogues I (N1‐ethyl‐C3‐carboxyl), 26b (N1‐ethyl‐C3‐carboxylate), and IIIc,d [N1‐alkyl‐C3‐(CH2)3COOC2H5].
Rearrangement of spiro[2H‐1‐benzopyran‐2,2′‐[2H]indoles] to pyrrolo[1,2‐a]indole derivatives
Authors: Martynaitis Vytas , Šačkus Algirdas , Berg Ulf
Published: March 2009

Heating of 1′‐(N‐substituted carbamoyl)methylspiro[2H‐1‐benzopyran‐2,2′‐[2H]indoles] with potassium hydroxide in ethanol yields diastereomeric 5a,13‐methano‐6H‐1,3‐benzoxazepino[3,2‐a]indole‐12‐carbox‐amides. Reduction of the latter with sodium borohydride affords 1,2,3,9a‐tetrahydro‐2‐hydroxyaryl‐9H‐pyrrolo[ 1,2‐a] indole‐3 ‐carboxamides.
Derivatives of 5‐Oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxylic acid: A tricyclic system useful for the synthesis of potential intercalators
Authors: Varvaresou Athanasia , Iakovou Kriton
Published: March 2009

The synthesis of a new series of 5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxamides 4a‐i and N1,N2‐Bis(5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐benzoyl)ethylenediamine (5) is reported starting from 2‐chloro‐3‐nitropyri‐dine. Fundamental steps of the synthetic pathway are i) preparation of 2‐(3‐nitro‐pyridin‐2‐ylamino)benzoic acid (1) via copper‐catalyzed condensation of 2‐chloro‐3‐nitropyridine with o‐anthranilic acid, ii) intramolecular cyclization of the acid 1 to 5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxylic acid (2b) upon treatment with concentrated sulfuric acid and oleum and iii) conversion of the acid 2 to the desired amides 4a‐i and 5. Compounds 4a‐i and 5 are oxygenated azaanalogs of phenazines, a wellknown series of intercalators with cytotoxic activity.
Determination of aromaticity indices of thiophene and furan by nuclear magnetic resonance spectroscopic analysis of their anilides
Authors: Lee Chang Kiu , Yu Ji Sook , Ji Young Ran
Published: March 2009

A series of m‐ and p‐substituted anilides of benzoic acid, 2‐thienoic acid, and 2‐furoic acid were prepared and their 1H and 13C nmr spectroscopic characteristics were examined. In general, good correlations were observed between the chemical shifts of proton and carbon signals of the acyl aromatic rings and the Hammett σ. Plots of the chemical shift values of the carbonyl carbons of the benzanilides against those of the 2‐thienamides and 2‐furamides gave an excellent correlation and the values of the slopes are 0.79 and 0.52, respectively, in dimethyl sulfoxide‐d6. The slopes could be considered as a set of aromaticity index.
Azinoiminophosphorane mediated synthesis of 5H, 7H‐1,2,4‐triazolo[1,5‐c][1,3]benzoxazepin‐7‐ones and 6H,8H‐1,2,4‐triazolo‐[1,5‐c][1,3]oxazepin‐6‐ones
Authors: Lee Chang Hoon , Kim Bong Gyu , Lee Kee‐Jung
Published: March 2009

The aza‐Wittig reactions of benzophenone‐, acetophenone‐ and benzaldehyde l‐[(triphenylphosphoranyl‐idene)amino]ethylidenehydrazones (4) with phthalic anhydride, 2,3‐dimethylmaleic anhydride and 7‐oxabi‐cyclo[2,2,l]hept‐5‐ene‐2,3‐dicarboxylic anhydride (5a) provide a new route to 5H,7H‐1,2,4‐triazolo[1,5‐c]‐[1,3]benzoxazepin‐7‐ones 8a‐c or 6H,8H‐1,2,4‐triazolo[1,5‐c][1,3]oxazepin‐6‐ones 8d‐h via the thermal reaction of the expected azinoimine lactones 6.
Synthesis of novel phenanthroline derivatives by 3+2 dipolar cycloadition reaction
Authors: Danac Ramona , Rotaru Alexandra , Drochioiu Gabi , Druta Ioan
Published: March 2009

Eleven new 1,10‐phenanthroline derivatives have been prepared by 3+2 dipolar cycloaddition reactions of 1,10‐phenanthrolinium‐ylides 7–12 in situ generated from corresponded salts, with dimethyl acetylene‐dicarboxylate and ethyl propiolate.
An efficient synthesis of 3‐hydroxychromone using niobium pentachloride
Authors: Constantino Mauricio Gomes , Júnior Valdemar Lacerda , Da Silva Gil Valdo José
Published: March 2009

A new and efficient 2‐step synthesis of 3‐hydroxychromone is described. Commercially available chromone is converted to the corresponding epoxide which is rearranged with niobium pentachloride to 3‐hydroxychromone in 61% overall yield.
Reactions of o‐quinones with α‐methyl‐ (or methylene) substituted phosphorus ylides. Synthesis of benzo[b]furan derivatives
Authors: Gautam Daman R. , Litinas Konstantinos E. , Fylaktakidou Konstantina C. , Nicolaides Demetrios N.
Published: March 2009

In Wittig reaction of some α‐methyl‐ and α‐methylene‐substituted phosphorus ylides with o‐quinones, benzo[b]furan derivatives were obtained via the cyclization of the o‐vinylphenols, initially formed from the tautomerization of the corresponding intermediate o‐quinone methides.
Syntheses and properties of dithia‐tetrahomodiaza‐calix[4]arenes bridged by cystine unit
Authors: Ito Kazuaki , Suzuki Akane , Ito Naoto , Teraura Hiroyuki , Ohba Yoshihiro
Published: March 2009

Dithia‐tetrahomodiaza‐calix[4]arenes were synthesized by the cyclization reactions of bis(3‐(chloro‐methyl)‐2‐hydroxyphenyl)sulfide with cystine peptides in moderate yields. Conformational analysis of the macrocycles by using nmr spectroscopy reveled that the cyclophanes adopt a cone‐like form as a preferable conformation and the cystine bridge moiety is incorporated in the cavity. The calixarene analogs can extract transion metals such as Zn2+ and Cu2+ ions from an aqueous phase into chloroform.
Synthesis of heteroaryl substituted α‐mercapto acids from thiomalic acid using hexafluoroacetone as protecting and activating reagent
Authors: Pumpor Ksenia , Windeisen Elisabeth , Burger Klaus
Published: March 2009

The synthesis of heterocyclic α‐mercapto acids starting from (RS)‐thiomalic acid using hexafluoroacetone as protecting and activating agent is described. The new compounds are useful building blocks for peptide and depsipeptide modification as well as for drug design.
7‐Methyl Trimethoprim Analogues as Inhibitors of the Folate Metabolizing Enzymes
Authors: Gangjee Aleem , Lin Xin , Queener Sherry F.
Published: March 2009

A series of 5‐(1‐phenylethyl)pyrimidines 2–10 (Table I) were designed and synthesized as potent and selective inhibitors of Pneumocystis carinii (P. carinii), Toxoplasma gondii (T. gondii) and Mycobacterium avium (M. avium) dihydrofolate reductases (DHFR). The structure of 2–10 incorporates a 7‐methyl group to increase the potency of monocyclic trimethoprim (TMP). The target compounds were synthesized by an acid catalyzed condensation of ethyl cyanoacetate and appropriately substituted benzaldehydes followed by a Michael addition using methyl copper‐lithium. The resulting adduct was cyclocondensed with guanidine to afford 2,6‐diamino‐4‐hydroxy‐5‐(1‐phenylethyl)pyrimidines 2–7. Both amino moieties of 2–4 were protected with pivaloyl groups and their 4‐hydroxy group chlorinated with phosphorus oxychloride. The resulting intermediates were subjected to hydrogenation and deprotection to afford 8–10. Compound 7 was a good inhibitor of DHFR, however the other compounds were poor inhibitors of P. carinii, T. gondii and M. avium DHFR.
Synthesis of N‐(Substituted aryl/cyclohexyl)‐N'‐[5‐bromo‐5‐nitro‐2‐oxido‐1,3,2‐dioxaphosphorinane‐2‐yl]ureas
Authors: Reddy P. Vasu Govardhana , Babu Y. Hari , Reddy C. Suresh
Published: March 2009

N‐(Substituted aryl/cyclohexyl)‐N'‐[5‐bromo‐5‐nitro‐2‐oxido‐1,3,2‐dioxaphosphorinane‐2‐yl]ureas RR'P(O)NHC(O)NHR' (5) were synthesized by the reactions of 2‐bromo‐2‐nitro‐1,3‐propanediol (4) with chlorides of aryl/cyclohexyl carbamidophosphoric acids (3) in the presence of triethylamine at room temperature. Their ir, 1H, 13C and 31P nmr spectral data are discussed.
The reaction of acetic acid 2‐selenoxo‐2H‐pyridin‐1‐yl esters with benzynes: A convenient route to Benzo[b]seleno[2,3‐b]pyridines
Authors: Narasimha Rao U. , Sathunuru Ramadas , Maguire John. A. , Biehl Ed
Published: March 2009

Benzyne and its 3,4,5,6‐tetraphenyl, 3‐ and 4‐methyl, 3‐methoxy and 4,5‐difluoro derivatives react with acetic acid 2‐selenoxo‐2H‐pyridin‐1‐yl esters 4a‐e to give benzo[b]seleno[2,3‐b]pyridines 10–15 in modest yields. The benzynes were generated by one or more of the following methods: diazotization of anthranilic acids 5a‐g with isoamyl nitrate; mild thermal decomposition of 2‐diazoniobenzenecarboxylate hydrochlorides 6a‐d treatment of (phenyl)[o‐(trimethylsilyl)phenyl]iodonium triflate (7) with tetrabutylammonium fluoride; and treatment of 2‐trimethylsilylphenyl triflates 8a‐c with cesium fluoride. In all the reactions, the corresponding 2‐(methylselenenyl)pyridines 16a‐d were also obtained suggesting that these reactions may involve selenium addition to benzyne via a SET (single electron transfer).
Simple and efficient cleavage reaction of the boc group in heterocyclic compounds
Authors: Nadia Klai , Malika Berredjem , Nawel Khettache , Yazid Belghit Med , Zine Régaïnia , Aouf Nour‐Eddine
Published: March 2009

Dedicated to the memory of Pr. Ladjama Daif A series of chiral cyclosulfamides have been synthesized by alkaline cyclisation starting from N‐benzoylamino acids (Ala, Val, Leu, Phe) derivatives and chlorosulfonyl isocyanate. A simplified and regioselective deprotection of the cyclic compounds (cyclosulfamides) containing the tert‐butyloxycarbonyl group (Boc) has been achieved in good yield by fusion under reduced pressure.
The synthesis of azoniadithia[6]helicenes
Authors: Sato Kiyoshi , Okazaki Shuichi , Yamagishi Takamichi , Arai Sadao
Published: March 2009

A new short‐step synthesis of 8a‐azonia[6]helicene (1) and the novel dithieno derivatives (2 and 3) is described. Double photocyclization of 2,8‐distyrylquinolizinium salt (8) gave 1 in 35% yield. Similarly, 2,8‐bis[2‐(2‐thienyl)vinyl]‐ and 2,8‐bis[2‐(3‐thienyl)vinyl]‐quinolizinium salts (9 and 10) afforded new azonia[6]helicenes containing two thiophene rings at the ends of helix, that is 7a‐azonia‐3,12‐dithia[6]helicene (2) and 7a‐azonia‐1,14‐dithia[6]helicene (3), in 43 and 35% yields, respectively. The total assignment of their 1H‐ and 13C‐nmr spectra was performed by utilizing two‐dimensional and NOE nmr spectroscopic methods.
Synthesis of α‐alkylidene‐γ‐butyrolactones via Ring‐cleavage/recyclization of 2‐Amino‐4,5‐dihydro‐3‐furancarboxamides
Authors: Okabe Fumi , Tagawa Yoshinobu , Yamagata Kenji
Published: March 2009

The reactions of 2‐amino‐4,5‐dihydro‐3‐furancarboxarnides 1a,b with cyanomethylene compounds (such as alkyl cyanoacetates and malononitrile) gave the corresponding ring‐opened products 2a‐f. Compounds 2a‐d reacted with methanesulfonic acid to give the corresponding α‐alkylidene‐γ‐butyrolactones 3a‐d. On the other hand, treatment of 2e,f with methanesulfonic acid yielded 3‐pyridinecarbonitrile derivatives 4a,b.
Synthesis of six new 2‐Aryl‐N‐biphenyl benzimidazoles and crystal structure of methyl 4′ [(2‐p‐Chlorophenyl‐1H‐benzimidazole‐1‐yl)‐methyl]biphenyl‐2‐carboxylate
Authors: Zhiming Zhou , Weifa Yu , Jun Zhang , Congxuan Yu , Xinqi Zhao
Published: March 2009

Six new 2‐aryl‐N‐biphenyl benzimidazoles were designed and synthesized, starting with O‐phenylenediamine and carboxylic acids via cyclization, followed by N‐alkylation. All new compounds were identified by H NMR, IR, MS spectra and elemental analysis. The crystal structure of methyl 4′‐[(2‐p‐chlorophenyl‐1H benzimidazole‐1‐yl)methyl]biphenyl‐2‐carboxylate (4f) was determined by single crystal X‐raydiffraction.
Photoaddition of thiocarboxylic acids to 2,3‐diallyltetraazathiapentalenes
Authors: Matsumura Noboru , Mori Osamu , Takeguchi Toshio , Okumura Yasuyuki , Mizuno Kazuhiko
Published: March 2009

Photoirradiation of acetone solutions of 2,3‐diallyl‐6,7‐dihydro‐5H‐2a‐thia(2a‐SIV)‐2,3,4a, 7a‐tetraazacyclopent[cd]indene‐ 1,4(2H,3H)‐dithione (1) in the presence of excess thioacetic acid and thiobenzoic acid afforded addition products, 2,3‐bis(3‐acetylthiopropyl)‐ and 2,3‐bis(3‐benzoylthiopropyl)‐6,7‐dihydro‐5H‐2a‐thia(2a‐SIV)2,3,4a, 7a‐tetraazacyclopent[cd]indene‐1,4(2H,3H)‐dithiones, respectively, in good yields. These photoaddition reactions were facilitated by the addition of oxygen.
Oxazoles formation during O‐alkylation of isonitroso‐naphthols. X‐ray structure of [1,2]naphthoquinone 1‐[O‐(4‐tert‐butyl‐benzyl)‐oxime] and 2‐(4‐tert‐butyl‐phenyl)napth[1,2‐d]oxazole
Authors: Astolfi Paola , Carloni Patricia , Castagna Riccardo , Greci Lucedio , Stipa Pierluigi , Rizzoli Corrado
Published: March 2009

1‐Nitroso‐2‐naphthol and 2‐nitroso‐1‐naphthol, both in the isonitroso form, react with benzyl bromides in THF and in the presence of triethylamine affording, in low yields, the corresponding O‐benzyl oximes and 2‐aryl naphthoxazoles in a 1:1 ratio, approximately. The structures of O‐benzyl oximes and naphthoxazoles isolated have been determined by X‐ray analysis.
Synthesis of novel 4,5‐diazafluoren‐9‐one derivatives and theoretical study of 3+2 cycloaddition reactions
Authors: Danac Ramona , Druta Ioan , Rotaru Alexandru , Ghirvu Constantin , Constantinescu Mircea
Published: March 2009

Some novel salts of 4,5‐diazafluoren‐9‐one N‐monosubstituted have been obtained by using Kröhnke method. The ability of 9‐oxo‐4,5‐diazafluorenium phenacylides (as 1,3‐dipoles) to react with activated symmetric dipolarophiles to give new heterocyclic compounds is presented. The new heterocyclic system of 10,10c‐diazacyclopenta[c]fluoren‐6‐one is illustrated by a series of derivatives. The cycloaddition reaction proceeds, according to the semiempirical study, via a concerted nonsynchronous mechanism.
The unexpected rearrangement of 1,5‐benzodiazepin‐2,4‐dione to a benzimidazol‐2‐one derivative during N,N'‐diglucosylation
Authors: Lakhrissi Brahim , Massoui Mohamed , Essassi El Mokhtar , Lequart Vincent , Joly Nicolas , Martin Patrick , Goethals Gérard
Published: March 2009

Reaction of 1,5‐benzodiazepin‐2,4‐dione with 3‐O‐substituted‐5,6‐anhydro‐1,2‐isopropylidene‐α‐D‐glucofuranose gave the unexpected N,N'‐di‐glucofuranosyl benzimidazol‐2‐one by a novel rearrangement and ring closure reaction. A mechanism is proposed.
Strongly fluorescent dipyrrinones—substituent effects
Authors: Boiadjiev Stefan E. , Lightner David A.
Published: March 2009

Bright yellow N,N'‐carbonyl‐bridged dipyrrinones (substituted 3H,5H‐dipyrrolo[1,2‐c:2′,1′‐f]pyrimidine‐3,5‐diones) were synthesized by reaction of the parent dipyrrinone with carbonyldiimidazole. Their solutions in organic solvents fluoresced strongly, with fluorescent quantum yields (ϕF)0.32‐0.92.
Biomimetic processes. IV. Carbocationic polymerization of isoprene initiated by dimethyl allyl alcohol
Authors: Puskas Judit E. , Peres Clément , Peruch Frédéric , Deffieux Alain , Dabney David E. , Wesdemiotis Chrys , Hayat‐Soytaş Serap , Lindsay Allia
Published: March 2009

In this article, we investigate a new bio‐inspired synthetic route towards NR homologs based on the carbocationic polymerization of isoprene initiated by dimethyl allyl alcohol (DMAOH)/TiCl4 or BF3.Et2O as the catalytic system. This study is the continuation of our studies related to the proof of principle that NR biosynthesis is based on a carbocationic mechanism. It is shown that using the biomimetic strategy of initiation by allylic carbocations, polyisoprene carrying a dimethyl allyl head group is produced almost exclusively via 1,4 addition, yielding repeating units with cis and trans configurations. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2181–2189, 2009
Mitochondrial impacts of insecticidal formate esters in insecticide‐resistant and insecticide‐susceptible Drosophila melanogaster
Authors: Song Cheol , Scharf Michael E
Published: March 2009

BACKGROUND: Previous research on insecticidal formate esters in flies and mosquitoes has documented toxicity profiles, metabolism characteristics and neurological impacts. The research presented here investigated mitochondrial impacts of insecticidal formate esters and their hydrolyzed metabolite formic acid in the model dipteran insect Drosophila melanogaster Meig. These studies compared two Drosophila strains: an insecticide‐susceptible strain (Canton‐S) and a strain resistant by cytochrome P450 overexpression (Hikone‐R).

RESULTS: In initial studies investigating inhibition of mitochondrial cytochrome c oxidase, two proven insecticidal materials (hydramethylnon and sodium cyanide) caused significant inhibition. However, for insecticidal formate esters and formic acid, no significant inhibition was identified in either fly strain. Mitochondrial impacts of formate esters were then investigated further by tracking toxicant‐induced cytochrome c release from mitochondria into the cytoplasm, a biomarker of apoptosis and neurological dysfunction. Formic acid and three positive control treatments (rotenone, antimycin A and sodium cyanide) induced cytochrome c release, verifying that formic acid is capable of causing mitochondrial disruption. However, when comparing formate ester hydrolysis and cytochrome c release between Drosophila strains, formic acid liberation was only weakly correlated with cytochrome c release in the susceptible Canton‐S strain (r2 = 0.70). The resistant Hikone‐R strain showed no correlation (r2 < 0.0001) between formate ester hydrolysis and cytochrome c release.

CONCLUSION: The findings of this study provide confirmation of mitochondrial impacts by insecticidal formate esters and suggest links between mitochondrial disruption, respiratory inhibition, apoptosis and formate‐ester‐induced neurotoxicity. Copyright © 2009 Society of Chemical Industry
Rethinking Regulatory Engagement Theory
Authors: Pham Michel Tuan , Avnet Tamar
Published: March 2009

We offer a constructive critique of Regulatory Engagement Theory (Higgins, E. T. (2006). Value from hedonic experience and engagement. Psychological Review, 113(3), 439–460.; Higgins, E. T., and Scholer, A. A. (2009). Engaging the consumer: The science and art of the value creation process. Journal of Consumer Psychology, 19(2).). After highlighting the major tenets of the theory and its main contributions, we identify some of its conceptual ambiguities. We then argue that the hedonic and intensity components of value may not be psychologically separable in that experiences acquire their hedonic quality through their intensity. We next discuss why the various determinants of strength of engagement proposed by the theory may not all operate through the same process. Even the regulatory fit phenomenon seems to involve more than one process. We conclude by suggesting that many strength‐of‐engagement effects may reflect feelings‐as‐information inferences consistent with the Generalized Affect‐as‐Information Model of judgment (GAIM; Pham, M. T. (2008). The lexicon and Grammar of Affect‐as‐Information: The GAIM. In M. Wanke (Ed.), Social psychology of consumer behavior. New York: Psychology Press.).
Guillotine tonsillectomy: a neglected technique
Authors: Sunkaraneni V S , Ismail-Koch H , Salib R J , Jain P K
Published: March 2009

Background:

Increased post-operative tonsillectomy haemorrhage rates have been observed following ‘hot’ tonsillectomy techniques, compared with ‘cold steel’ dissection. Post-tonsillectomy haemorrhage rates and the degree of blood loss during guillotine tonsillectomy have not been reported in the recent literature.

Methods:

This retrospective case note review assessed the degree of blood loss during guillotine tonsillectomy, as measured by the number of tonsil swabs used, and the post-tonsillectomy haemorrhage rate.

Results:

In a group of 168 patients, no tonsil swabs were used in 13.1 per cent of cases, and less than two tonsil swabs were used in 41.1 per cent of cases.

Conclusion:

Guillotine tonsillectomy, when performed by the method described in this article, resulted in minimal intra-operative blood loss in 54 per cent of cases, and appeared to have comparable post-tonsillectomy haemorrhage rates to cold steel dissection techniques.
Retrenching Incapacity Benefit: Employment Support Allowance and Paid Work
Authors: Piggott Linda , Grover Chris
Published: March 2009

In October 2008 in the UK Incapacity Benefit (IB) (the main income replacement benefit for sick and disabled claimants) was replaced by the Employment and Support Allowance (ESA) for new claimants. Drawing upon recent work on the retrenchment of welfare benefits and services this paper examines the context for the changes, the marketisation of the job placement services for ESA claimants and the extension of conditionality to sick and disabled benefit claimants. The paper argues that the introduction of ESA is a good example of the retrenchment of benefits for the majority of sick and disabled people. The paper concludes that ESA can be interpreted as creating a group of disadvantaged people through which the private sector can profit.
Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model
Authors: Susaki Etsuo , Nakayama Keiko , Yamasaki Lili , Nakayama Keiichi I.
Published: March 2009

Although p27 and p57 are structurally related cyclin-dependent kinase inhibitors (CKIs), and are thought to perform similar functions, p27 knockout (p27
KO
) and p57
KO
mice show distinct phenotypes. To elucidate the in vivo functions of these CKIs, we have now generated a knock-in mouse model (p57
p27KI
), in which the p57 gene has been replaced with the p27 gene. The p57
p27KI
mice are viable and appear healthy, with most of the developmental defects characteristic of p57
KO
mice having been corrected by p27 knock-in. Such developmental defects of p57
KO
mice were also ameliorated in mice deficient in both p57 and the transcription factor E2F1, suggesting that loss of p57 promotes E2F1-dependent apoptosis. The developmental defects apparent in a few tissues of p57
KO
mice were unaffected or only partially corrected by knock-in expression of p27. Thus, these observations indicate that p57 and p27 share many characteristics in vivo, but that p57 also performs specific functions not amenable to substitution with p27.
Non-boronized compared with boronized operation of ASDEX Upgrade with full-tungsten plasma facing components
Authors: Kallenbach A. , Dux R. , Mayer M. , Neu R. , Pütterich T. , Bobkov V. , Fuchs J.C. , Eich T. , Giannone L. , Gruber O. , Herrmann A. , Horton L.D. , Maggi C.F. , Meister H. , Müller H.W. , Rohde V. , Sips A. , Stäbler A. , Stober J.
Published: March 2009

After completion of the tungsten coating of all plasma facing components, ASDEX Upgrade has been operated without boronization for 1 1/2 experimental campaigns. This has allowed the study of fuel retention under conditions of relatively low D co-deposition with low-Z impurities as well as the operational space of a full-tungsten device for the unfavourable condition of a relatively high intrinsic impurity level. Restrictions in operation were caused by the central accumulation of tungsten in combination with density peaking, resulting in H–L backtransitions induced by too low separatrix power flux. Most important control parameters have been found to be the central heating power, as delivered predominantly by ECRH, and the ELM frequency, most easily controlled by gas puffing. Generally, ELMs exhibit a positive impact, with the effect of impurity flushing out of the pedestal region overbalancing the ELM-induced W source. The restrictions of plasma operation in the unboronized W machine occurred predominantly under low or medium power conditions. Under medium-high power conditions, stable operation with virtually no difference between boronized and unboronized discharges was achieved. Due to the reduced intrinsic radiation with boronization and the limited power handling capability of VPS coated divertor tiles (≈10 MW m−2), boronized operation at high heating powers was possible only with radiative cooling. To enable this, a previously developed feedback system using (thermo-)electric current measurements as approximate sensor for the divertor power flux was introduced into the standard AUG operation. To avoid the problems with reduced ELM frequency due to core plasma radiation, nitrogen was selected as radiating species since its radiative characteristic peaks at lower electron temperatures in comparison with Ne and Ar, favouring SOL and divertor radiative losses. Nitrogen seeding resulted not only in the desired divertor power load reduction but also in improved energy confinement, as well as in smaller ELMs.
Correction for phylogeny, small number of observations and data redundancy improves the identification of coevolving amino acid pairs using mutual information
Authors: Buslje Cristina Marino , Santos Javier , Delfino Jose Maria , Nielsen Morten
Published: March 2009

Motivation: Mutual information (MI) theory is often applied to predict positional correlations in a multiple sequence alignment (MSA) to make possible the analysis of those positions structurally or functionally important in a given fold or protein family. Accurate identification of coevolving positions in protein sequences is difficult due to the high background signal imposed by phylogeny and noise. Several methods have been proposed using MI to identify coevolving amino acids in protein families.

Results: After evaluating two current methods, we demonstrate how the use of sequence-weighting techniques to reduce sequence redundancy and low-count corrections to account for small number of observations in limited size sequence families, can significantly improve the predictability of MI. The evaluation is made on large sets of both in silico-generated alignments as well as on biological sequence data. The methods included in the analysis are the APC (average product correction) and RCW (row–column weighting) methods. The best performing method was APC including sequence-weighting and low-count corrections. The use of sequence-permutations to calculate a MI rescaling is shown to significantly improve the prediction accuracy and allows for direct comparison of information values across protein families. Finally, we demonstrate how a lower bound of 400 sequences <62% identical is needed in an MSA in order to achieve meaningful predictive performances. With our contribution, we achieve a noteworthy improvement on the current procedures to determine coevolution and residue contacts, and we believe that this will have potential impacts on the understanding of protein structure, function and folding.

Contact:  cmb@qb.ffyb.uba.ar; mniel@cbs.dtu.dk
Core fucosylation of E‐cadherin enhances cell–cell adhesion in human colon carcinoma WiDr cells
Authors: Osumi Daisuke , Takahashi Motoko , Miyoshi Eiji , Yokoe Shunichi , Lee Seung Ho , Noda Katsuhisa , Nakamori Shoji , Gu Jianguo , Ikeda Yoshitaka , Kuroki Yoshio , Sengoku Kazuo , Ishikawa Mutsuo , Taniguchi Naoyuki
Published: March 2009

α1,6‐Fucosyltransferase (Fut8), an enzyme that catalyzes the introduction of α1,6 core fucose to the innermost N‐acetylglucosamine residue of the N‐glycan, has been implicated in the development, immune system, and tumorigenesis. We found that α1,6‐fucosyltransferase and E‐cadherin expression levels are significantly elevated in primary colorectal cancer samples. Interestingly, low molecular weight population of E‐cadherin appeared as well as normal sized E‐cadherin in cancer samples. To investigate the correlation between α1,6‐fucosyltransferase and E‐cadherin expression, we introduced α1,6‐fucosyltransferase in WiDr human colon carcinoma cells. It was revealed that the low molecular weight population of E‐cadherin was significantly increased in α1,6‐fucosyltransferase‐transfected WiDr cells in dense culture, which resulted in an enhancement in cell–cell adhesion. The transfection of mutated α1,6‐fucosyltransferase with no enzymatic activity had no effect on E‐cadherin expression, indicating that core fucosylation is involved in the phenomena. In α1,6‐fucosyltransferase knock down mouse pancreatic acinar cell carcinoma TGP49 cells, the expression of E‐cadherin and E‐cadherin dependent cell–cell adhesion was decreased. The introduction of α1,6‐fucosyltransferase into kidney epithelial cells from α1,6‐fucosyltransferase–/– mice restored the expression of E‐cadherin and E‐cadherin‐dependent cell–cell adhesion. Based on the results of lectin blotting, peptide N‐glycosidase F treatment, and pulse‐chase studies, it was demonstrated that the low molecular weight population of E‐cadherin contains peptide N‐glycosidase F insensitive sugar chains, and the turnover rate of E‐cadherin was reduced in α1,6‐Fucosyltransferase transfectants. Thus, it was suggested that core fucosylation regulates the processing of oligosaccharides and turnover of E‐cadherin. These results suggest a possible role of core fucosylation in the regulation of cell–cell adhesion in cancer. (Cancer Sci 2009; 100: 888–896)
Assessment of incidence of inhibitors in patients with haemophilia
Authors: VAN DER BOM J. G. , TER AVEST P. , VAN DEN BERG H. M. , PSATY B. M. , WEISS N. S.
Published: March 2009

Summary.  In patients with haemophilia, the development of neutralizing allo‐antibodies (‘inhibitors’) while receiving the deficient clotting factor is relatively common during the patients’ initial treatment. Among treated patients with haemophilia who do not develop inhibitors early on, the later incidence is considerably lower. Therefore, the evaluation of potential risk factors for their tendency to give rise to inhibitors is best performed separately in previously untreated and previously treated patients. We discuss potential implications of study design and analysis choices on the validity of inferences from studies assessing inhibitor incidences.
The expression of ERα, ERβ and PR in lobular carcinoma in situ of the breast determined using laser microdissection and real‐time PCR
Authors: Green Andrew R , Young Peter , Krivinskas Sophie , Rakha Emad A , Claire Paish E , Powe Desmond G , Ellis Ian O
Published: March 2009

Aims:  To determine the status of oestrogen receptor (ER) subtypes (ERα and ERβ) in lobular carcinoma in situ (LCIS) of the breast.

Methods and results:  Forty‐seven cases of LCIS and six cases with normal breast lobules were subjected to immunohistochemistry and evaluated for ERα, ERβ and progesterone receptor (PR) expression. mRNA for ERα, ERβ1 and ERβ2 were quantified in LCIS and normal lobules using laser microdissection coupled with real‐time polymerase chain reaction. LCIS showed a higher level of steroid receptor protein expression than normal lobules. There was no difference in ERβ1 gene or ERβ protein expression between normal lobules, pure LCIS, or LCIS associated with invasive breast cancer. No significant difference in expression of either ERα or ERβ was found between pure LCIS and LCIS associated with invasive cancer. However, PR was significantly lower in those cases of LCIS with associated invasive than in those without synchronous invasive disease.

Conclusions:  Increased expression of steroid receptors in LCIS suggests their possible role in the biology of LCIS and, for PR, could influence the predisposition of women diagnosed with LCIS to develop invasive breast carcinoma.
Expression of glucose‐regulated stress protein GRP78 is related to progression of melanoma
Authors: Zhuang Liquing , Scolyer Richard A , Lee C Soon , McCarthy Stanley W , Cooper Wendy A , Zhang Xu D , Thompson John F , Hersey Peter
Published: March 2009

Aims: Glucose‐regulated protein 78 (GRP78) is a protein translated in response to endoplasmic reticulum (ER) stress that has been implicated in the pathogenesis and resistance to therapy of a variety of cancers. The aim of this study was to investigate its expression and role in the development and progression of human melanoma.

Methods and results: The immunohistochemical expression of GRP78 in naevi, primary melanoma and melanoma metastases from 171 patients was correlated with clinicopathological factors and patient survival. The GRP78 immunoreactivity score (IRS) was 0.2 in compound naevi, 0.65 in dysplastic naevi, 4.65 in naevi adjacent to primary melanoma, 2.4 in melanomain situ, 11.2 in thin (≤1.0 mm) and 18.1 in thick (>1.0 mm) primary melanoma. It was 18 and 17.3 in subcutaneous and lymph node metastases, respectively (P < 0.0001). GRP78 expression was positively correlated with increasing tumour thickness (P = 0.001) and with increasing dermal tumour mitotic index (P = 0.0004). Disease‐free survival (χ2 = 8.0703,P = 0.0045) and overall survival (χ2 = 6.2633,P = 0.0123) in melanoma patients with IRS >25 were significantly lower than in melanoma patients with IRS <25.

Conclusions: GRP78 expression appears to correlate with known correlates of melanoma progression and survival and requires further evaluation as a prognostic biomarker in melanoma.
Chronic sorrow in parents of children with type 1 diabetes
Authors: Bowes Susan , Lowes Lesley , Warner Justin , Gregory John W.
Published: March 2009

Title.  Chronic sorrow in parents of children with type 1 diabetes.

Aim.  This paper reports on a study exploring parents’ longer‐term experiences of having a child with type 1 diabetes.

Background.  Parents of children with type 1 diabetes may experience a grief reaction at diagnosis similar to that normally associated with bereavement, but little is known about their long‐term emotional adaptation. Chronic sorrow, a sustained but intermittent grief reaction, is identified in adults with diabetes but has not previously been explored in relation to parents.

Methodology.  In‐depth interviews were conducted in 2007 with a convenience sample of 17 parents of children with type 1 diabetes 7–10 years after diagnosis. Data were explored within a theoretical framework of grief, loss, adaptation, and change.

Findings.  Parents had adapted to the needs of diabetes management but most had not ‘come to terms’ with the diagnosis. They experienced a resurgence of grief at critical times during their child’s development and some, particularly mothers, became upset during their interviews, even though these took place 7–10 years after their child’s diagnosis. Mothers elaborated more on their emotions than fathers, but continuing feelings associated with grief, such as anger and guilt, were expressed by both fathers and mothers.

Conclusion.  Greater understanding of parents’ long‐term emotional responses and recognition that grief may never resolve in these parents may enable healthcare professionals to provide appropriate and timely support at critical times.
Infectious agents and lymphoma development: molecular and clinical aspects
Authors: Ferreri A. J. M. , Ernberg I. , Copie‐Bergman C.
Published: March 2009

This review is focused on the role of infectious agents in the development of some lymphoma entities. Associations involving bacterial infections mostly regard marginal zone B‐cell lymphomas of mucosa‐associated lymphoid tissue (MALT)‐type. Some paradigmatic examples of these associations include theHelicobacter pylori‐related gastric MALT lymphoma and the more recently reported links betweenChlamydophila psittaciand ocular adnexal MALT lymphomas andBorrelia burgdorferiand cutaneous MALT lymphomas. The well‐documented association between Epstein–Barr virus infection and related lymphoproliferative disorders are analysed as an example of lymphotropic virus with tumourigenic activity. Molecular, biological and clinical features as well as therapeutic implications of these associations are analysed and future perspectives in this field are discussed.
The effects of Pierce's disease on leaf and petiole hydraulic conductance in Vitis vinifera cv. Chardonnay
Authors: Choat Brendan , Gambetta Greg A. , Wada Hiroshi , Shackel Kenneth A. , Matthews Mark A.
Published: March 2009

In this study, we test the hypothesis that the symptoms of Pierce's Disease (PD) result from the occlusion of xylem conduits by the bacteria Xylella fastidiosa (Xf ). Four treatments were imposed on greenhouse‐grown Vitis vinifera cv. Chardonnay: well‐watered and deficit‐irrigated plants with and without petiole inoculation with Xf. The hydraulic conductance of the stem‐petiole junction (kjun) and leaves (kleaf) were measured, and Xf concentrations were established by quantitative polymerase chain reaction (qPCR). Leaf hydraulic conductance decreased with increasing leaf scorch symptoms in both irrigation treatments. The positive relationship between Xf concentration and symptom formation in deficit‐irrigated plants suggests that water‐stress increases susceptibility to PD. In field‐grown vines, water relations of symptomatic leaves were similar to naturally senescing leaves but differed from green control leaves. Overall, these results suggest that the development of PD symptoms represents a form of accelerated senescence as part of a systemic response of the plant to Xf infection.
Detection of Puccinia striiformis in Latently Infected Wheat Leaves by Nested Polymerase Chain Reaction
Authors: Wang Xiaojie , Tang Chunlei , Chen Jinlong , Buchenauer Heinrich , Zhao Jie , Han Qingmei , Huang Lili , Kang Zhensheng
Published: March 2009

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating wheat diseases worldwide, especially in temperate regions with cool moist weather conditions. The identification of the pathogen in infected plants based on morphological or physiological criteria before sporulation is labour‐intensive and time‐consuming. To accelerate and simplify the process of detection, a nested Polymerase Chain Reaction (PCR) assay was developed for specific and sensitive detection of Pst. Specific primers Psta‐Psts were designed according to a genome‐specific sequence of Pst. In nested PCR, with a 10‐fold dilution series of template DNA, the detection limit was 2 pg DNA in the first PCR with the primers Psta‐Psts. The second round PCR was then performed using amplified products from the first PCR as the template and Nesta‐Nests as the primers. An amplification signal was detectable even when only 2 fg of P. striiformis f. sp. tritici DNA was used as the template in nested PCR. With nested PCR, the sensitivity of detection was enhanced 1000 fold. Using extracts from stripe rust‐infected wheat leaves, the fungus could be determined in the leaves before symptom appearance. The assay provides a rapid and sensitive method for detection of P. striiformis f. sp. tritici in latently infected leaves of overwintering wheat plants.
Occurrence and Distribution of Microdochium and Fusarium Species Isolated from Durum Wheat in Northern Tunisia and Detection of Mycotoxins in Naturally Infested Grain
Authors: Kammoun Lobna Gargouri , Gargouri Samia , Hajlaoui Mohamed Rabeh , Marrakchi Mohamed
Published: March 2009

An outbreak of Fusarium Head Blight of durum wheat occurred in 2004 being localized in sub‐humid and higher semi‐arid region of Northern Tunisia. A mycological survey carried out throughout these regions, revealed that 78% of the prospected fields were infested. Results of the morphological and molecular identification, showed that the most common species isolated from diseased wheat spikes was Microdochium nivale var. nivale (63.5%), followed by Fusarium culmorum (26%), F. pseudograminearum (9%) and F. avenaceum (1.5%). To evaluate mycotoxin content of naturally infected grain, the amounts of trichothecene mycotoxin deoxynivalenol (DON) in harvested grain from 45 fields were quantified by RIDASCREEN DON Enzyme Immunoassay Kit (ELISA). This study showed that the infection levels in freshly harvested grain were very low and the maximum deoxynivalenol (DON) level of the positive samples was 53 ppb. This is the first report on the natural occurrence of DON in naturally infected wheat grain sampled from Northern Tunisia.