bluuebunny/crossref_metadata_2025 huggingface dataset:
The birch reduction of heterocyclic compounds V Birch reduction of 2‐ and 5‐acylfuran‐3‐carboxylic acids and reductive elimination of 2‐(arylmethoxymethyl)furan‐3‐carboxylic acids
Authors: Ohta Yasuo , Doe Matsumi , Morimoto Yoshiki , Kinoshita Takamasa
Published: March 2009

The Birch reduction of 2‐ and 5‐acylfuran‐3‐carboxylic acid 1 and 4 gave 2‐acyl‐2,3‐dihydrofuran‐3‐carboxylic acid 2 and 5‐acyltetrahydrofuran‐3‐carboxylic acid 5, respectively. Further examination of the reductive elimination was also studied on 2‐(arylmethoxymethyl)furan‐3‐carboxylic acids 7.
Synthesis of isomeric triazolopyrrolopyrimidines
Authors: Dave Chaitanya G. , Shah Rina D.
Published: March 2009

4‐Hydrazino‐7H‐pyrrolo[2,3‐d]pyrimidines (4) were cyclocondensed with formic acid or triethyl orthoformate to give 7H‐1,2,4‐triazolo[1,5‐c]pyrrolo[3,2‐e]pyrimidines (5) and 7H‐1,2,4‐triazolo[4,3‐c]pyrrolo‐[3,2‐e]pyrimidines (6) respectively. The [4,3‐c]‐isomers (6) were rearranged into thermodynamically more stable [1,5‐c]‐isomers (5). The identical compounds (5) were prepared using another route by reacting 3‐amino‐4‐imino‐7H‐pyrrolo[2,3‐d]pyrimidines (3) with formic acid or triethylorthoformate. Reaction of 2‐amino‐3‐cyanopyrroles (1) with triethyl orthoformate followed by hydrazinolysis afforded (3) via the formation of N‐ethoxymethylene‐2‐amino‐3‐cyanopyrroles (2).
A comparative study of conventional conditions versus microwave irradiation for the preparation of novel 1,2‐dihydro‐2‐imino‐7‐methyl‐1,6(6H)‐naphthyridin‐5‐ones
Authors: Heber Dieter , Stoyanov Edmont V.
Published: March 2009

The synthesis of novel 1,6‐naphthyridines 6 with potential activity against tuberculosis is described using the reaction sequence 2←4←6. Depending on the ring N‐substitution of the 4‐alkylamino‐6‐methyl‐2(1H)‐pyridones 1 and 2 the electrophilic attack of the Vilsmeier reagent gives rise to the formation of the exocyclic N‐formyl derivatives 3 from 1 and the corresponding 3‐carbaldehydes 4 from 2. 1,2‐Dihydro‐2‐imino‐7‐methyl‐1,6(6H)‐naphthyridin‐5‐ones 6a‐j are prepared by the Knoevenagel reaction of 4 with CH‐acidic nitriles 5. These reactions are carried out using a comparative study of conventional conditions (room temperature or reflux) versus microwave irradiation.
A new route to functionalized 3‐aminopyridazines by ANRORC type ring transformation of 1,2,4‐triazines with carbon nucleophiles
Authors: Rykowski Andrzej , Wolinska Ewa , Van Der Plas Henk C.
Published: March 2009

The reaction of 3‐chloro‐6‐phenyl‐1,2,4‐triazine 1a with carbon nucleophiles 2ad bearing a cyano substituent at a carbanionic center has been studied. In all reactions the formation of the corresponding 3‐aminopyridazines 3ad takes place via ANRORC mechanism involving addition of the nucleophile at position 5 in compound 1a, ring opening with breaking of the N4C5 bond and intramolecular ring closure of the resulting open‐chain intermediate. A 15N study with labeled phenylacetonitrile 2a* has shown that the nitrogen atom of the exocyclic amino group of 3‐amino‐4,6‐diphenylpyridazine 3a was originally present in phenylacetonitrile.
Synthesis of derivatives of thiophene using methyl 2‐isothiocyanatobenzoate
Authors: Deck L. M. , Turner S. D. , Deck J. A. , Papadopoulos E. P.
Published: March 2009

A variety of 2‐substituted thiophenes is readily obtained from 2‐(2‐thienyl)‐4H‐3,l‐benzothiazin‐4‐one (2), which is formed when thiophene reacts with methyl 2‐isothiocyanatobenzoate (1) in the presence of anhydrous stannic chloride.
Synthesis of 5‐(functionalized acyl)‐1,3‐dialkyl‐substituted barbituric and 2‐thiobarbituric acids
Authors: Zoorob Hanafi H. , Ismail Mohamed A. , Strekowski Lucjan
Published: March 2009

A sodium derivative of 1,3‐dimefhylbarbituric acid or 1,3‐diethyl‐2‐thiobarbituric acid undergoes an efficient monoacylation at C5 by the reaction with ω‐chloroalkanoyl chloride or diacid dichloride in the presence of pyridine in tetrahydrofuran. A nucleophilic displacement of the chlorine in a 5‐chloroacetyl‐bartiburate can be accomplished by using a one‐pot procedure. By contrast, a similar transformation of a 5‐(chlorobutanoyl)barbituric acid requires intramolecular cyclization in the presence of a nonnucleophilic base followed by treatment with a nucleophile of the resultant 5‐[4,5‐dihydro(3H)‐2‐furylidene]barbiturate.
Inverse electron‐demand 1,3‐dipolar cycloaddition reactions of cyclooctyne with pyridinium bis(methoxycarbonyl)methylides
Authors: Matsumoto Kiyoshi , Hayashi Naoto , Ikemi Yukio , Toda Mitsuo , Uchida Takane , Aoyama Kinuyo , Miyakoshi Yoshihiro
Published: March 2009

Cyclooctyne underwent 1,3‐dipolar cycloaddition with pyridinium bis(methoxy‐carbonyl)methylides to afford the corresponding indolizines (8‐methoxycarbonyl‐7‐azatricyclo[7.6.0.02‐7]pentadeca‐1,3,5,8‐tetraenes) in good to moderate yields. Some molecular orbital considerations are also described on this reaction compared with the results on the reaction of pyridinium dicyanomethylides with cyclooctyne.
Synthesis of novel alkylamino zinc(II) phthalocyanines
Authors: Rodríguez Myriam E. , Strassert Cristian A. , Awruch Josefina , Dicelio Lelia E.
Published: March 2009

The synthesis of tetramethyl‐tetraphthalimidomethyl‐phthalocyaninato zinc(II) (6) and tetramethyl‐tetraaminomethyl‐phthalocyaninato zinc(II) (7) is described.
Reactions of 1‐amino‐5‐benzoyl‐4‐phenyl‐1H‐pyrimidine‐2‐one with carboxylic anhydrides: Experimental data and AM1 calculations
Authors: Önal Zülbiye , Sanpinar Emin , İlhan Ilhan Özer
Published: March 2009

1‐Amino‐5‐benzoyl‐4‐phenyl‐1H‐pyrimidine‐2‐one 1 reacts with several carboxylic anhydrides 2a‐d under different conditions and gives new amide and imide derivatives. The structure of these compounds, 3a‐d, are determined by spectroscopic methods. Electronic and geometric structures of reactants, transition states, intermediates and final products of the reaction are calculated by the AM1 method. Transition states are further confirmed by vibrational analysis (computation of force constants analytically) and characterized by the corresponding imaginary vibration modes and frequencies.
Polycyclic N‐Heterocyclic Compounds. 56 Reaction of N‐(5,6‐Dihydro[1]benzoxepino[5,4‐d]pyrimidin‐4‐yl)amidine or Its Amide Oxime Derivatives with Hydroxylamine Hyrdochloride
Authors: Sasaki Kenji , Zhang Ying‐Xue , Okuda Kensuke , Hirota Takashi
Published: March 2009

The reactions of N‐(5,6‐dihydro[1]benzoxepino[5,4‐ d]pyrimidin‐4‐yl)amidines or its amide oxime derivatives with hydroxylamine hydrochloride gave abnormal cyclization products via a ring cleavage of pyrimidine component accompanied with a ring closure of [1,2,4]oxadiazole.
Difurocoumarins: Psoralen analogs as photochemotherapeutic agents
Authors: Chilin A. , Manzini P. , Caffieri S. , Rodighiero P. , Guiotto A.
Published: March 2009

New tetracyclic psoralen‐like compounds have been synthesized, which are characterized by two furan rings angularly condensed on the coumarin nucleus and are therefore called difurocoumarins. This structural feature may favour the intercalation into the DNA helix and then monofunctionally photoreaction with DNA bases. Their synthesis started from 5,7‐dihydroxy‐4‐methylcoumarin, which was condensed with α‐halo‐ketones; the resulting ketoethers were then cyclized to give the title compounds.
Differentiation between 1,2,4,5‐tetraoxanes and 1,2,4,5,7,8‐hexaoxonanes using 1H and 13C NMR analyses
Authors: Dong Yuxiang , Vennerstrom Jonathan L.
Published: March 2009

The proton and carbon resonance spectra of ten pairs of 1,2,4,5‐tetraoxanes and 1,2,4,5,7,8‐hexa‐oxonanes derived from acyclic and cyclic ketones have been recorded. A reliable method for distinguishing between 1,2,4,5‐tetraoxanes and 1,2,4,5,7,8‐hexaoxonanes by inspection of their chemical shifts, signal number, signal shape, and dynamic features has been developed. This method provides a rapid structural assignment of 1,2,4,5‐tetraoxanes and 1,2,4,5,7,8‐hexaoxonanes without using vapor pressure osmometry, isotope labeling or low temperature NMR techniques.
Configurational assignments of the diastereomers of 3,3′‐(1,2‐ethanediyl)bis[2‐(3‐fluorophenyl)‐5‐methyl‐4‐thiazolidinone] derivative with four stereogenic centers
Authors: Vigorita Maria Gabriella , Ottaná Rosaria , Monforte Francesca , Previtera Tindara , Maccari Rosanna
Published: March 2009

Diastereomers of antiinflammatory/analgesic and antihistaminic 3,3′[(1,2‐ethanediyl)bis(2‐aryl‐4‐thiazo‐lidinone)] derivatives possessing two stereogenic centers (indicated as BIS 2*C) have been widely investigated in recent years. The 5,5′‐dimethyl analogues (BIS 4*C), now reported, have been synthesized by reaction of (±) α‐mercaptopropionic acid and N,N'‐di(3‐fluorobenzyliden)ethylenediamine. Because the 2 and 2′carbons bear the same groups and similarly the 5 and 5′ carbons, and the latter groups are different from the former, four enantiomeric pairs and two meso forms exist in this situation. These diastereomers were identified by the concerted use of nmr spectroscopy and hplc on chiral stationary phase.
Study of the basicity of some 1,2‐diazinium ylids
Authors: Caprosu M. , Roman M. , Olariu I. , Dima S. T. , Mangalagiu I. , Petrovanu M.
Published: March 2009

In this paper we present a study concerning the basicity of some new carbanion monosubstituted pyridazinium, 3‐methyl‐pyridazinium, 3‐(p‐halogenophenyl)‐pyridazinium and phtalazinium ylids. The pka values of the conjugated acids (salts) of ylids have been experimentaly determinated. Consequently, we have evaluated their basicity (kb,) using the titration curves. The basicity depends mainly on the structure of the ylids carbanion itself, however the heterocycle's structures also has some influence on bacisity. Having in view the basicity, we have established certain correlations between basicity, structure and stability of the analised ylids.
Hypervalent iodine in synthesis 50: A novel method of synthesis of selenazoles by cyclocondensation of selenoamides and alkynyl(phenyl)iodonium salts
Authors: Zhang Peng‐Fei , Chen Zhen‐Chu
Published: March 2009

A novel method for the synthesis of selenazoles by cyclocondensation of primary selenoamides and alkynyl(phenyl)iodomium salts and the reaction mechanism are reported. The synthetic method is simple, mild and the yields are high.
Diastereoselective synthesis of (2R,4S,5S)‐(+)‐5‐(2,2‐dichloroacetamido)‐ 4‐(4‐nitrophenyl)‐2‐aryl‐1,3‐dioxanes
Authors: Jun Liu , Jun Li , Shaorong Yang , Hua Li , Quanyuan Hu , Hansheng Xu , Xianming Hu
Published: March 2009

(2R,4S,5S)‐(+)‐5‐(2,2‐Dichloroacetamido)‐4‐(4‐nitrophenyl)‐2‐aryl‐1,3‐dioxanes 3–8 were synthesized with high diastereoselectivity and good yields. The structures of acetals were determined and the configurations were confirmed by 2D‐NMR (NOESY) and X‐ray crystallographic analysis.
Synthesis of fused pyrimidines with N‐, S‐heterocyclic moieties by double‐annelation reaction
Authors: Chowdhury A. Z. M. Shaifullah , Shibata Yasuyuki
Published: March 2009

A variety of tri‐ and tetracyclic hetero systems were obtained by reaction of heteroaromatic ortho‐aminoesters or ortho‐aminonitriles with iminothioether, yielding double‐annelation of a thiazolo[3,2‐a]‐pyrimidine, pyrimido[2,l‐b]thiazine, imidazo[1,2‐a]pyrimidine, and pyrimido[1,2‐a]pyrimidine moieties in a one‐pot process.
Photoinduced molecular rearrangements. Some comments on the ring‐photoisomerization of 1,2,4‐oxadiazoles into 1,3,4‐oxadiazoles
Authors: Buscemi Silvestre , Pace Andrea , Vivona Nicolò , Caronna Tullio
Published: March 2009

The ring‐photoisomerization of 3‐amino‐ and 3‐methylamino‐5‐phenyl‐1,2,4‐oxadiazoles into the corresponding 2‐amino‐ and 2‐methylamino‐5‐phenyl‐1,3,4‐oxadiazoles has been reinvestigated by examining the effect of a base on the photoreaction. On irradiating at λ = 254 nm in methanol, yields of the ring‐photoisomers were found to be significantly enhanced by the addition of triethylamine (TEA) in the photoreaction medium. By contrast, irradiation of the 3‐amino‐5‐phenyloxadiazole in acetonitrile containing TEA gave an almost complete photoreduction into benzoylguanidine, while few percent of the ring photoisomer were detected. Furthermore, the pyrene‐sensitized photolysis of 3‐amino‐5‐phenyloxadiazole in acetonitrile containing triethylamine also gave benzoylguanidine but no traces of the ring photoisomer.
An easy route to 2‐substituted‐2,3‐dihydro‐5(7)H‐oxazolo[3,2‐a]pyrimidin‐5‐ones and 7‐ones starting from the corresponding 2‐amino‐2‐oxazolines
Authors: Forfar I. , Guillon J. , Massip S. , Léger J.‐M. , Jarry C. , Fayet J.‐P.
Published: March 2009

The isomeric 2‐substituted‐7(5)‐methyl‐2,3‐dihydro‐5(7)H‐oxazolo[3,2‐a]pyrimidin‐5‐ones 3a‐b and 7‐ones 2a‐b,7a were synthesized by cyclocondensation from the 5‐substituted‐2‐amino‐2‐oxazolines 1a‐b with biselectrophiles. In boiling ethanol, the reaction of 1a‐b with acetylenic esters led to a mixture of 2a‐b,7a with a small amount of (E)‐2‐N‐(2‐ethoxycarbonylethylene)‐5‐substituted‐2‐iminooxazolines 5a‐b. The ring annulation between 1a‐b and diketene gave the 2‐substituted‐7‐hydroxy‐7‐methyl‐2,3,6,7‐tetrahydro‐5H‐oxazolo[3,2‐a]pyrimidin‐5‐ones 4a‐b which can be easily dehydrated to provide the 2‐substituted‐7‐methyl‐2,3‐dihydro‐5H‐oxazolo[3,2‐a]pyrimidin‐5‐ones 3a‐b.
Synthesis and NMR spectroscopic studies of optically active derivatives of γ‐aminobutenoic acids and 2‐amino‐pyrrolin‐4‐ones
Authors: Petroliagi Margarita , Igglessi‐Markopoulou Olga
Published: March 2009

An efficient method for the preparation of optically active derivatives of γ‐amino‐butenoic acids and their cyclic derivatives, 2‐amino‐pyrrolin‐4‐ones, from α‐amino acids is described. Partial racemization accompanies the formation of initial unsaturated γ‐amino‐β‐hydroxy esters 5–8, as determined by chiral HPLC.
An improved synthesis of enantiomerically pure RWJ 69442, a development candidate for the treatment of benign prostatic hyperplasia
Authors: Kuo Gee‐Hong , Prouty Catherine , Murray William V. , Shah Rekha D.
Published: March 2009

This report describes an improved synthesis of enantiomerically pure (S)‐2‐[4‐(Dimethylamino)phenyl]‐2,3‐dihydro‐N‐[2‐hydroxy‐3‐[4‐[2‐(1‐methylethoxy)‐phenyl]‐1‐piperazinyl]propyl]‐1,3‐dioxo‐1H‐isoindole‐5‐carboxamide (RWJ 69442), a potent and selective αla‐adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia. The synthesis highlights less hazardous reagents, easier purification and higher enantiomeric purity. The N‐benzyl‐N—t‐butoxycarbonyl amine 6 could serve as an enantiomerically pure chiral building block for asymmetric synthesis.
On the mechanism and stereochemistry of the formation of β‐lactam derivatives of 2,4‐disubstituted‐2,3‐dihydro‐benzo[1,4]diazepines
Authors: Wang Hong‐Zhong , Zhou Xin , Xu Jia‐Xi , Jin Sheng , Li Yue‐Ming , Chan AlbertS. C.
Published: March 2009

2‐Chloro‐4‐phenyl‐2a‐(4′‐methoxyphenyl)‐3,5‐dihydroazatetracyclic [1,2‐d]benzo [ 1,4]diazepin‐1 ‐one (IIIa) and 2‐chloro‐4‐methyl‐2a‐(4′‐methoxyphenyl)‐3,5‐dihydroazatetracyclic[1,2‐d]‐benzo[1,4]diazepin‐1‐one (IIIb) were synthesized. 1‐Benzoyl‐2‐phenyl‐4‐(4′‐methoxyphenyl)[1,4]‐benzodiazepine (IIa) was formed through benzoylation of starting material 2‐phenyl‐4‐(4′‐methoxyphenyl)‐[1,4]benzodiazepine (Ia) with the inversion of seven‐member ring boat conformation. The thus formed β‐lactams should have four pairs of stereoisomers. However, only one pair of enantiomers (2S,2R,4R) and (2R,2aS,4S) was obtained. The mechanism and stereochemistry of the formation of these compounds were studied on the basis of nmr spectroscopy and further confirmed by X‐ray diffraction.
The synthesis of 1‐[(substituted)pyrazol‐5‐yl]‐iminomethyl‐2‐nitroiminoimidazolidine and its derivatives
Authors: Chen Wei‐Qiang , Ji Gui‐Yu
Published: March 2009

In this article 1‐[(substituted)pyrazol‐5‐yl]iminomethyl‐2‐nitroimino imidazolidines (II) and their derivatives were synthesized. All the compounds were verified by elemental analysis, 1H NMR and IR. In the reaction of II with halides, two different results were observed.
Investigation the chemical reactivity of positions N‐3, C‐5 and C6‐methyl group in biginelli type compounds and synthesis of new dihydropyrimidine derivatives
Authors: Mirzaei Y. R. , Azamat H. , Namazi H.
Published: March 2009

The compounds 5‐ethoxycarbonyl‐1,6‐dimethyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(lH)‐one (5) and 5‐ethoxycarbonyl‐1‐phenyl‐6‐methyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(lH)‐one (1) were prepared by the Biginelli condensation method and they converted to eight N‐3 substituted dihydropyrimidines using NaH and various electrophiles (ClCO2Et, TsCl, Ac2O, AcCl and PhCOCl). Compound (1) was mono‐brominated at the C6‐methyl group using bromine solution. Reaction of the bromo derivative with amino nucleophiles such as methyl amine and cyclohexyl amine produced two pyrrolo‐pyrimidine derivatives. All the compounds except 5‐ethoxycarbonyl‐1‐phenyl‐6‐methyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(lH)‐one (4) were purified by recrystallization methods. The structure of all the new compounds was confirmed using FT‐ir,1H nmr,13C nmr spectral and elemental analyses methods.
Synthesis of new heterocondensed pteridines
Authors: Chowdhury A. Z. M. Shaifullah , Shibata Yasuyuki , Morita Masatoshi , Kaya Kunimitsu , Hiratani Kazuhisa
Published: March 2009

Reaction of 2‐aminopyrazine 1 with isothiocyanate, isocyanate or dithioketal reagent furnished pteridines 3,4 in good yield. Thioxo compound 3a was chlorinated, methylated and subsequently displaced by amines. A simple one‐step synthesis of heterocondensed pteridines 8–13 by reaction of 2‐aminopyrazine with various imino thioacetals was described 8–13.
The reaction of homophthalic acid and some aza analogues with vilsmeier reagent: a reinvestigation
Authors: Deady Leslie W. , Rodemann Thomas
Published: March 2009

Homophthalic acid and its pyrido and 8‐methylquinolino analogues with dimethylformamide/phosphoryl chloride at 0° give the appropriate 4‐(dimethylaminomethylene)isochroman‐1,3‐dione (2a, 2b, 2c, respectively). Under the literature conditions for conversion of 2a to 2‐methyl‐1‐oxo‐1,2‐dihydroisoquinoline‐4‐carboxylic acid (3a), the aza analogues give instead 7‐hydroxy‐5‐oxo‐5H‐pyrano[4,3‐b]pyridine‐8‐carbox‐aldehyde (5b) and 3‐hydroxy‐6‐methyl‐1‐oxo‐1H‐pyrano[4,3‐b]quinoline‐4‐carboxaldehyde (5c), respectively. Modified conditions were required to isolate analogues 3b and 3c. Further, while reaction of 2a with hydrogen chloride in methanol gave the known change to methyl 1‐oxo‐1H‐isochromene‐4‐carboxylate (4), 2b and 2c gave only products of oxa‐ring cleavage. Methyl 2‐(cis‐2‐hydroxyvinyl)‐8‐methylquinoline‐3‐carboxylate (8) was the main product from 2c, while a novel quinolizinium species (11) was formed in good yield from 2b.
Synthesis and characterization of some coumarins with two hydroxy or methoxy substituents
Authors: Fall Yagamare , Santana Lourdes , Uriarte Eugenio
Published: March 2009

The first synthesis of the 6‐hydroxy‐4‐methoxycoumarin (5) was carried out in 25 % overall yield from 6‐methoxy‐4‐hydroxycoumarin (1) by hydrolysis of the methoxy group and subsequent selective methylation of the hydroxyl group at position 4. The 1H and 13C NMR data of compounds 1–6 are reported.
Ring transformations of heterocyclic compounds. XXI. Diastereoselective built‐up of an aroylcyclohexadiene moiety as second spiro‐connected ring at spiroindolines by pyrylium ring transformation
Authors: Zimmermann Thomas
Published: March 2009

2,4,6‐Triarylpyrylium perchlorates 1 react with methyleneindolines 3 in situ generated from the corresponding methylindolium salts 2, which are spiro‐fused with a cycloalkane, benzanellated cycloalkene or a heterocyclic system. These diastereoselective 2,5‐[C4+C2] pyrylium ring transformations are carried out in the presence of triethylamine/acetic acid in boiling ethanol to give the dispiroindolines 4 with a trans configuration of the more bulky substituents at the cyclohexadiene ring. By the same type of transformation the dispiro compounds 7/10 with an additional fused benzene ring are obtained from the pyrylium salt 1a and 6/9, the benzo‐fused analogues of 3. Spectroscopic data of the transformation products as well as their mode of formation are discussed.
A convenient synthesis of 5‐ and 8‐nitroquinazoline‐2,4‐dione derivatives
Authors: Aziane D. , Soukri M. , El Hakmaoui A. , Lazar S. , Akssira M. , Essassi E. M. , Guillaumet G.
Published: March 2009

3‐Nitrophthalic acid 1 was converted selectively to the two regioisomeric monoesters 2 and 3, which were subsequently transformed via Curtius rearrangement to the corresponding 5‐ and 8‐nitroquinazoline‐2,4‐diones 4 and 5, respectively. The reduction of the nitro group produced 5‐ and 8‐aminoquinazoline‐2,4‐diones 6 and 7, respectively, in good yields. The condensation of compounds 7b and 7c with carbon disulfide in pyridine afforded tricyclic derivatives 9, which are analogues of the HIV‐1 reverse transcriptase inhibitor 4,5,6,7‐tetrahydro‐5‐methylimidazo[4,5,1‐jk][1,4]benzodiazepin‐2(1H)‐one(TIBO).
Synthesis of spirolactones by 1,3‐dipolar cycloadditions to methyl (S)‐3‐[(E)‐cyanomethylidene]‐2‐oxotetrahydrofuran‐5‐carboxylate
Authors: Pirc Samo , Rečnik Simon , Škof Marko , Svete Jurij , Golič Ljubo , Meden Anton , Stanovnik Branko
Published: March 2009

Dedicated to Professor Emeritus Miha Tišler on the occasion of his 75th birthday

Treatment of methyl (S)‐5‐[(E)‐(dimethylamino)methylidene]‐2‐oxotetrahydrofuran‐5‐carboxylate (2) with potassium cyanide in acetic acid gave (S)‐5‐[(E)‐cyanomethylidene]‐2‐oxotetrahydrofuran‐5‐car‐boxylate (3), which was used as chiral dipolarophile in 1,3‐dipolar cycloadditions. Reactions of 3 with diazomethane (4) and nitrile oxides 5a‐c afforded spirolactones 6–8 in 24‐34% diastereomeric excess, while with diazomethane (4) in the presence of triethylamine, methyl 3‐cyanomethyl‐2‐methoxyfuran‐5‐carboxylate (12) was obtained.
A comparative study on the synthesis of 4‐alkyl‐1,3‐diarylpyrazoles using microwave irradiation and conventional thermal methods
Authors: Selvi S. , Perumal P. T.
Published: March 2009

A convenient synthesis of 4‐alkyl‐1,3‐diarylpyrazoles (2) under microwave irradiation as well as conventional thermal method using Vilsmeier cyclization is reported. Microwave irradiation has resulted in the reduction of time from hours to seconds.
Study of the heterocyclization of vic‐substituted hydrazides of acetylenylpyrazolecarboxylic acids into N‐amino pyrazolopyridinones
Authors: Vasilevsky Sergei F. , Mshvidobadze Elena V. , Elguero José
Published: March 2009

We report a new and efficient methodology to prepare N‐amino pyrazolo[4,3‐c]pyridin‐4‐ones 4 and N‐amino pyrazolo[3,4‐c]pyridin‐4‐ones 8 from vic‐acetylenyl/hydrazido pyrazoles. The procedure involves the intermediate synthesis of methyl esters of acetylenyl‐pyrazole carboxylic acids and the subsequent cyclization under a variety of conditions.
Tautomerism of diazepines fused with pyrimidine rings
Authors: Chebanov Valentin A. , Desenko Sergey M. , Shishkin Oleg V. , Kolos Nadezhda N. , Komykhov Sergey A. , Orlov Valery D. , Meier Herbert
Published: March 2009

The tautomerism of 1,4‐diazepines fused with pyrimidine rings was studied by means of nmr spec‐troscopy, X‐ray analysis and quantum chemical calculations. It was found that in the case of 6,8‐diphenyl‐pyrimido[4,5‐b][1,4]diazepin‐4‐ols (7a ‐ e) the enamine form is more stable than the diimine form. This result is rationalized with the electron‐withdrawing effect of the 4‐hydroxypyrimidine ring and with the formation of intermolecular hydrogen bonds. In contrast to 7a ‐ e, the 6,8‐diaryl‐2,3,4,7‐tetrahydro‐1,3‐dimethyl‐1H‐pyrimido[4,5‐b][1,4]diazepine‐2,4‐diones (9a, c, f) exist in the diimine form.
Synthesis and 1,3‐dipolar cycloaddition reactions of N‐Aryl‐C, C‐dimethoxycarbonylnitrones
Authors: Tomioka Yukihiko , Nagahiro Chie , Nomura Yumiko , Maruoka Hiroshi
Published: March 2009

Arylnitroso compounds 1–3 easily reacted with dimethyl bromomalonate to give the corresponding N‐aryl‐C,C‐dimethoxycarbonylnitrones (4–6). Treatment of C,C‐dimethoxycarbonyl‐N‐( 1‐naphthyl)nitrone (4) with acetylene compounds (dimethyl acetylenedicarboxylate, methyl 2‐butynoate or ethyl phenylpropiolate) caused 1,3‐dipolar cycloaddition to furnish the corresponding 1H‐benz[g]indolines (7a‐c). In a similar manner, the reactions of nitrones 5 and 6 with acetylene compounds afforded the corresponding indolines 9a‐c and 11a‐c together with 4‐oxazolines 13a‐c and 14a‐c.
Structural Aspects of 5‐methylthio‐1‐oxa‐6,6a δIV‐dithia‐2‐azapentalenes
Authors: Chollet‐Krugler Marylégne , Burgot Jean‐Louis , Finner E. , Christen Marie‐Odile
Published: March 2009

Alkylation of 5‐[1‐hydroxyiminoalkyl]‐1,2‐dithiole‐3‐thiones using methyl iodide in the presence of sodium hydroxide gives derivatives which may be considered as being 5‐methylthio‐1‐oxa‐6,6a δIV‐dithia‐2‐azapentalenes with quantitative yields. The structure of oxadithiazapentalene attributed to the alkylation products is founded on X‐ray analysis and NMR and IR data.
Synthesis of new uracil non‐nucleoside derivatives as potential inhibitors of HIV‐1
Authors: El‐Essawy Farag A. , El‐Brollosy Nasser R. , Pedersen Erik B. , Nielsen Claus
Published: March 2009

6‐(2‐Phenylethyl) and 6‐cyclohexyl 5‐cyanouracils (1a,b) were synthesized and reacted with chloromethyl ethyl ether, benzyl chloromethyl ether, chloromethyl methyl sulfide and (2‐acetoxyethoxy)methyl bromide. New uracil analogues of (S)‐DHPA were synthesized by reaction of compounds (1a,b) with ((S)‐2,2‐dimethyl‐1,3‐dioxolane‐4‐yl) alkylp‐toluenesulfonate.
Structural study of highly halogenated dihydropyridine derivatives as potential calcium channel modulators
Authors: Suárez Margarita , Salfrán Esperanza , Ochoa Estael , Verdecia Yamila , Alba Livan , Martín Nazario , Seoane Carlos , Martínez‐Alvarez Roberto , De Armas Hector Novoa , Blaton Norbert M. , Peeters Oswald M. , De Ranter Camiel J.
Published: March 2009

Two dihydropyridines endowed with fluorine atoms (3) and fluorine and chlorine atoms (4) have been synthesized and structurally characterized by experimental X‐ray analyses and theoretical calculations at the semiempirical (AMI) and ab initio (HF/6–31G*) levels. The results show that these compounds meet the required criteria to act as potential calcium channel modulators.
Synthesis of pyrazole‐fused heterocycles by thermal rearrangement ofN‐aziridinylimino ketenimines
Authors: Lee Kee‐Jung , Kim Dong‐Wook , Kim Boo‐Geun
Published: March 2009

The reaction ofN‐aziridinylimino carboxamides 11 with a mixture of triphenylphosphine, carbon tetrachloride, and triethylamine in dichloromethane (Appel's condition) provides a new route to pyrazole‐fused heterocycles such as 2,3‐dihydro‐lH‐imidazo[1,2‐b]pyrazoles 15 and 9,10‐dihydro‐47H‐pyrazolo[5,l‐b]‐[1,3]benzodiazepines 17viathe thermal rearrangement of the expectedN‐aziridinylimino ketenimines12.
Evaluation of N‐hydroxymethylphthalimide in alkaline medium: Novel entry to the tricyclic [1,3]oxazepine core via an intramolecular π and O‐cationic cyclization
Authors: Cul Armelle , Pesquet Anthony , Daïch Adam , Chihab‐Eddine Abderrahim , Marchalín Štefan
Published: March 2009

Fused isoindolo[1,3]benzo(or thieno)oxazepines 8a,b and one of their positional isomers aromatic tricyclic N,O‐acetals 13b are reported to occur efficiently in a three‐step sequence from N‐hydroxy‐methylphthalimide (6). The key step of this methodology is the intramolecular arylation of an endocyclic and/or exocyclic N‐acyliminium cation. The mechanism leading to these species, in particular to a tricyclic lactam 13b, is discussed.
Oxazoline chemistry part III. Synthesis and characterisation of [2‐(2′‐anilinyl)‐2‐oxazolines] and some related compounds
Authors: Button Karen M. , Gossage Robert A.
Published: March 2009

The syntheses and characterisation of a series of chiral and achiral 2‐(aminophenyl)‐2‐oxazolines and some related compounds is reported. All of the derivatives have been produced by a one‐step procedure involving the treatment of isatoic anhydride (i.e.[2H]‐3, 1‐benzoxazine‐[1H‐2,4‐dione:1) or its 5‐chloro analogue with a slight excess of appropriate amino‐alcohols. In most cases, anhydrous ZnCl2is shown to be an effective Lewis acid catalyst for this reaction at reflux temperature in high boiling aromatic solvents (PhCl or PhMe). Oxazolines have been readily formed usingrac‐2‐amino‐1‐butanol, (S)‐phenylglycinol, 2‐methyl‐2‐amino‐1‐propanol and(1S,2R)or(IR,2S)‐cis‐1‐amino‐2‐indanol; yields range from 85% to 22%. The use of aminoalcohols such as 2‐ethanolamine, (±)‐2‐amino‐1‐phenyl‐1‐propanol or 3‐amino‐1‐propanol (to give the corresponding 4,5‐dihydro‐1,3‐oxazine) results in poor yields. The use of other Lewis acid catalysts (silicic acid, Cd(acac)2·2H2O, CuCl2·2H2O, InCl3) or higher temperatures did not improve the yields with these latter two substrates. Benzoxazoles and N‐substituted benzoxazoles can also be obtained in reasonable yields from1using 2‐aminophenol (36%) or 2‐amino‐3‐hydroxypyridine (45%).
Preparation of 3‐(10′‐halo‐9′‐anthracenyl) isoxazolecarboxylic esters
Authors: Han Xiaochun , Twamley Brendan , Natale Nicholas R.
Published: March 2009

The 10‐halo (Cl or Br) anthracene‐9‐nitrile oxides (1a,b) were obtained directly from the treatment of 9‐anthracenylaldoxime with N‐halosuccinimide (NCS or NBS) in DMF. The 3‐(10′‐halo‐9′‐anthracenyl)‐5‐isoxazolecarboxylic esters (5a,b and 6a,b) were prepared via 1,3‐dipolar cycloaddition between the obtained nitrile oxides 1a (or 1b) and two different dipolarophiles: ethyl β‐pyrrolidinocrotonate (an enamine of ethyl acetoacetate) or dimethyl acetylenedicarbox‐ylate (DMAD) respectively. The 10 (or 10′)‐ position of the anthracene in either anthracene‐9‐nitrile oxide or 3‐(9′‐anthracenyl) isoxazole molecules (3,4) is readily halogenated by N‐halosuc‐cinimide in DMF. X‐ray studies showed that 5a possesses two aromatic ring systems that lie at 74.4° from coplanarity. The bond linking the two ring systems is 1.4893(18) Å, indicating only partial conjugation between the two ring systems. The crystal lattice showed unique head‐to‐tail intermolecular stacking of anthracene rings.
Synthesis, characterization and biological activity of bis(3‐Aryl‐1‐hexahydropyrimidinyl)methanes. Novel heterocyclic polyamine derivatives
Authors: Bisceglia Juan Á , García María B. , Massa Rosana , Magri María L. , Zani Mariana , Gutkind Gabriel O. , Orelli Liliana R.
Published: March 2009

A method is described for the synthesis of bis(3‐aryl‐1‐hexahydropyrimidinyl)methanes 1, by condensation of N‐aryl‐1,3‐propanediarnines 2 with formaldehyde. The reaction mechanism involves N‐arylhexahydropyrimidines 3 as intermediates. Such compounds can also be prepared efficiently by a methylene exchange reaction between bis‐hexahydropyrimidines 1 and the corresponding diamines 2. The antimicrobial activity of compounds 1 was evaluated by the disk diffusion method and some of them showed moderate to good growth inhibition activity.
The synthesis of 8‐hydroxyquinazoline derivatives and their acid‐base interactions
Authors: Kudelko Agnieszka , Zieliński Wojciech
Published: March 2009

The reaction of N‐(2‐R1‐oxyphenyl)benzimidoyl chlorides with cyanamide derivatives in the presence of titanium tetrachloride as a catalyst has yielded some new 4‐amino‐8‐R1‐oxy‐2‐phenylquinazolines. pKa values have been determined for these compounds and the influence of substituents at the basicity of the parent system has been discussed. Some investigations on the methyl‐quinazolinyl ether cleavage in different medium have been done yielding the appropriate hydroxyquinazoline derivatives. In those cases when the deprotection of 4‐amino‐8‐methoxy‐2‐phenylquinazoline was carried in aqueous acidic solutions, the formation of the hydrolysis products 3,4‐dihydro‐2‐phenyl‐4‐quinazolone derivatives was observed as well.
Tandem Michael‐addition/cyclization synthesis and EGFR kinase inhibition activity of pyrido[2,3‐d]pyrimidin‐7(8H)‐ones
Authors: Boros Eric E. , Thompson James B. , Wood Edgar R. , McDonald O. Bradley , Spitzer Timothy D. , Sefler Andrea M. , Reep Bryan R.
Published: March 2009

5‐Methoxy and 5‐anilinopyrido[2,3‐d]pyrimidin‐7(8H)‐ones 2a‐2f were obtained by a tandem Michael addition‐cyclization reaction of methanol and anilines with pyrimidinylpropynoate 5. Methoxy derivative 2a was obtained in 62% yield by treatment of 5 with methanol and potassium carbonate. Anilino derivatives 2b‐2f were prepared in 31–71% yields by reacting 5 with the corresponding anilines in refluxing methanol. This methodology accomplishes Michael‐addition and pyridopyrimidinone ring formation in one‐pot and affords the desired products in reasonable yield without chromatography. Propynoate 5 did not react with 4‐cyanoaniline under these conditions. Reaction of 5 with 2‐aminopyridine gave the unexpected arylpyrido[2,3‐d]pyrimidinone 8 in 58% yield and reaction of 5 with imidazole afforded Michael‐adduct 9 in 69% yield. Compounds 2a and 5 were submicromolar inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase.
Studies with enaminones: Synthesis and chemical reactivity of 2‐(4‐dimethylamino‐2‐oxobut‐3‐enyl)‐isoindole‐1,3‐dione and of 4‐(4‐dimethylamino‐2‐oxobut‐3‐enyloxy)‐2H‐phthalazin‐1‐one
Authors: Al‐Mousawi Saleh , John Elizabeth , Al‐Kandery Najat
Published: March 2009

The title compounds were synthesized via condensing acetonylphthalimide and 4‐acetonyloxyphthalazine‐1‐one with dimethylformamide dimethylacetal (DMFDMA). The reaction of these enaminones with electrophiles and nucleophiles is reported as a route to polyfunctional heteroaromatics.
Synthesis of trifluoromethylated pyrido[2,3‐d]pyrimidine‐2,4‐diones from 6‐aminouracils and trifluoromethylated pyrazolo[3,4‐b]‐pyridines from 5‐aminopyrazoles
Authors: Takahashi Masahiko , Nagaoka Hironori , Inoue Kazuhiro
Published: March 2009

5 or 7‐Trifluoromethyl‐1,2,3,4‐tetrahydropyrido[2,3‐d]pyrimidine‐2,4‐diones 3, 5, 10, 13 and 4‐ or 6‐trifluoromethylpyrazolo[3,4‐b]pyridines 15, 16, 19, 21 were prepared from 6‐aminouracils and 5‐aminopyrazoles, respectively, in good yields by the use of building blocks such as 4,4,4‐trifluoro‐1‐phenyl‐1,3‐butanedione, 1,1,1‐trifluoro‐4‐phenyl‐3‐buten‐2‐one, 4‐ethoxy‐1,1,1‐trifluoro‐3‐buten‐2‐one, and ethyl trifluoroacetoacetate.
Synthesis of some fused β‐carbolines including the first example of the pyrrolo[3,2‐c]‐β‐carboline system
Authors: Condie Glenn C. , Bergman Jan
Published: March 2009

Condensation of 1‐methyl‐β‐carboline‐3‐carbaldehyde with ethyl azidoacetate and subsequent thermolysis of the resulting azidopropenoate was used to [c] annulate a pyrrole ring onto the β‐carboline moiety, thus producing the first example of the pyrrolo[3,2‐c]‐β‐carboline ring system. The latter ring system results from cyclization at the C‐4 carbon, whereas cyclization at the N‐2 nitrogen atom also occurs to form a pyrazolo[3,2‐c]‐β‐carboline ring system. Condensation of β‐carboline‐1‐carbaldehyde with ethyl azidoacetate produced a non‐isolable intermediate, which immediately underwent cyclization, however in this case cyclization occurred via attack at the ester and the azide remained intact. The resulting 5‐azidocanthin‐6‐one was transformed to the first examples of 5‐aminocanthin‐6‐ones. β‐Carboline‐1,3‐dicarbaldehyde failed to give an acceptable reaction with ethyl azidoacetate, but did undergo selective condensation with dimethyl acetylene dicarboxylate at the C‐1 carbaldehyde with concomitant cyclization to form a highly functionalized 2‐formyl‐canthine derivative.
Hantzsch reaction of 3‐(2‐bromoacetyl)‐4‐hydroxy‐chromen‐2‐one. Synthesis of 3‐(thiazol‐4‐yl)‐4‐hydroxy coumarines
Authors: Sukdolak S. , Solujić S. , Manojlović N. , Vuković N. , Krstić L. J.
Published: March 2009

3‐Acetyl‐4‐hydroxy‐chromen‐2‐one (1) was brominated with phenyltrimethylammonium tribromide to afford 3‐(2‐bromoacetyl)‐4‐hydroxy‐chromen‐2‐one (2) whose reactions with thiourea, thioacetamide and ammonium dithiocarbamate gave respectively 3‐(2‐amino‐thiazol‐4‐yl)‐4‐hydroxy‐, 4‐hydroxy‐3‐(2‐phenyl‐thiazol‐4‐yl)‐ and 4‐hydroxy‐3‐(2‐mercapto‐thiazol‐4‐yl)chromen‐2‐one. In a similar manner, com pound 2 was treated with four 1‐substituted‐2‐thioureas and thiobenzamide to give the corresponding 4‐hydroxy‐3‐(thiazol‐4‐yl)‐chromen‐2‐one derivatives.
The synthesis of novel crown ethers, part X, 4‐propyl‐and 3‐ethyl‐4‐methylchromenone‐crown ethers
Authors: Tiftikçi Esra , Erk ÇAkil
Published: March 2009

Starting from ethyl propionylacetate, and ethyl 2‐ethylacetoacetate we prepared 4‐propyl‐7,8‐, 4‐propyl‐6,7‐, 3‐ethyl‐4‐methyl‐7,8‐ and 3‐ethyl‐4‐methyl‐6,7‐dihydroxy‐2H‐chromenones which were allowed to react with the bis‐dihalides or ditosylates of glycols in DMF/Na2CO3 to afford the 6,7‐ and 7,8‐chromenone derivatives of 12‐crown‐4, 15‐crown‐4 and 18‐crown‐6. The products were identified using ir, 13C and 1H nmr, ms and high resolution mass spectroscopy. The cation selectivities of chromenone crown ethers with Li+, Na+ and K+ cations were estimated from the steady state emission fluorescence spectra of free and cation complexed chromenone macrocyclic ethers in acetonitrile.
Alkyl heterocycles in heterocyclic synthesis (II): Novel synthesis of isoquinoline, thiazolopyridine, and thieno[2,3‐b]pyridine derivatives
Authors: Abu Elmaati Tarek M.
Published: March 2009

Treating 5‐(4‐phenylcarboxamido)‐3‐cyano‐4‐methylpyridin‐2(1H)thione (3) with elemental sulfur yielded thienopyridine 4. Compound 4 reacts with acrylonitrile to give isoquinoline 7. Compound 7 was also, prepared from 3 and methylenemalononitrile. Reaction of 3 with dimethylacetylene dicarboxylate (DMAD) gave the pyridothiazole 9. Also, 3 reacted with N,N‐dimethylchloroacetamide (10) to afford compound 11 which further reacted with the reagents 12, 13 and 14 providing the thieno[2,3‐b]pyridine derivatives 15, 16 and 17 respectively.
Benzo[1,2‐c:3,4‐c']bis[1,2,5]selenadiazole, [1,2,5]selenadiazolo‐[3,4‐e]‐2,1,3‐benzothiadiazole, furazanobenzo‐2,1,3‐thiadiazole, furazanobenzo‐2,1,3‐selenadiazole and related heterocyclic systems
Authors: Cillo Catherine M. , Lash Timothy D.
Published: March 2009

The first synthesis of benzo[1,2‐c:3,4‐c']bis[1,2,5]selenadiazole has been developed starting from commercially available 4‐nitrobenzo‐2,1,3‐selenadiazole. Improved syntheses of the related heterocycles [1,2,5]selenadiazolo[3,4‐e]‐2,1,3‐benzothiadiazole, furazanobenzo‐2,1,3‐thiadiazole and furazanobenzo‐2,1,3‐selenadiazole are also reported.
The preparation of benzoisothiazolo[1,2‐b][1,2]isoquinolin‐11‐one‐1,1‐dioxides from dilithiated ortho‐toluic acids and lithiated methyl 2‐(aminosulfonyl)benzoate
Authors: Dunn S. Patrick , Walters Matthew J. , Metz Clyde R. , Beam Charles F. , Pennington William T. , Krawiec Mariusz
Published: March 2009

Select dilithiated ortho‐toluic acids were prepared in excess lithium diisopropylamide and condensed with methyl 2‐(aminosulfonyl)benzoate followed by a twofold cyclization of intermediates to afford benzoisothiazolo[1,2‐b][1,2]isoquinolin‐11‐one‐1,1‐dioxides, a new fused‐ring heterocyclic system.
Chemical variability in propolis from Santiago del Estero, Argentina, related to the arboreal environment as the sources of resins
Authors: Chaillou Lucrecia L , Nazareno Mónica A
Published: March 2009

BACKGROUND: Propolis composition is extremely variable and depends on the plant resin sources that grow around the apiary. Polyphenols have been reported to be responsible of its pharmacological and biological properties. The contents of polyphenols and flavonoid aglycones were studied in propolis from different provenances to correlate these contents with the nature of the flora surrounding the hive.

RESULTS: Nineteen of these bioactive substances were identified in 30 samples classified into three arboreal categories according to their main species. A noticeable variability was observed in the concentration of each component depending on the plant origin of the samples. Higher amounts were found for pinocembrin (0.2–102.3 g kg−1), quercetin (0.08–86.6 g kg−1) and chrysin (0.8–18.8 g kg−1). Salicylic, 4‐hydroxybenzoic, benzoic, ferulic and gallic acids were other remarkable constituents.

CONCLUSION: Statistical significant differences in polyphenol and flavonoid contents were observed among arboreal groups, while very strong linear correlations were found between polyphenol and flavonoid contents for all the samples as well as for all the groups (R2% > 87). Copyright © 2009 Society of Chemical Industry
Sales by multi‐product retailers: a comment
Authors: Loy Jens‐Peter , Weiss Christoph R.
Published: March 2009

Immanent to the retail business is its multiproduct nature. In a recent issue of this journal Richards (2006) introduces a multiproduct model for perishable food items. Richards concludes that depth and breadth of sales are complementary marketing tools to increase store sales. He also provides empirical support for this hypothesis. We will show in the following that Richards' model does not suggest a complementarity between depth and breadth of sales. Instead, these tools are substitutes in his model. Therefore, the interpretation of his empirical result has to be reconsidered. Copyright © 2009 John Wiley & Sons, Ltd.
SysML modeling of off‐the‐shelf‐option acquisition for risk mitigation in military programs
Authors: Constantine James A. , Solak Senay
Published: March 2009

Off‐the‐Shelf software, hardware, and subsystem assemblies have been accepted by system engineers, project managers, designers, and, most importantly, the customer as an essential ingredient to the successful and rapid deployment of deliverable military systems. The Department of Defense (DoD) acquisition community almost always expects the prime contractor to incorporate the Off‐The‐Shelf‐Option (OTSO) within their system design, whether it is a military tank, software defined radio, or advance tactical fighter aircraft. Clearly, system engineers and program managers have an obligation to mitigate risks when using the OTSO in DoD programs. Part of risk mitigation means having in place predefined processes, methodologies, and models that revisit and evaluate risks throughout the lifecycle of the program or project. In this paper, we develop models and expand upon current methodologies that provide guidance, risk mitigation, analysis, and strategies to system engineers and program managers when implementing the OTSO in military systems. We present OTSO acquisition models using Object Management Group System Modeling Language (OMG SysML™), which we refer to as SysML throughout the paper. Specifically, we utilize Use Cases, a State Diagram, a Requirements Diagram, and an Activity Diagram within the SysML language to model acquisition, sustainment, and risk mitigation phases of an OTSO. The purposes of the models are to illustrate how the processes are tightly coupled and to put forward a concept that “glues” the processes together. Additionally, the models demonstrate the interdependencies required among the various disciplines within an organization to successfully deploy and maintain a system utilizing an OTSO. © 2009 Wiley Periodicals, Inc. Syst Eng
Nanomedicine for respiratory diseases
Authors: Swai Hulda , Semete Boitumelo , Kalombo Lonji , Chelule Paul , Kisich Kevin , Sievers Bob
Published: March 2009

Treatment of respiratory diseases and infections has proved to be a challenging task, with the incidence of these ailments increasing worldwide. Nanotechnology‐based drug and gene delivery systems offer a possible solution to some of the shortfalls of the current treatment regimen. Nanobased drug delivery systems have revolutionised the field of pharmacotherapy by presenting the ability to alter the pharmacokinetics of the conventional drugs to extend the drug retention time, reduce the toxicity and increase the half‐life of the drugs. Delivery of exogenous genes to the airway epithelium in vivo has been limited by several physiological barriers, resulting in the low success rate of these systems. With the advent of nanotechnology, DNA compacted with cationic polymers to produce nanoparticles has exhibited a significant increase in the transfection efficiencies. With nanoparticulate drug/gene delivery systems, specific cells can be targeted by functionalising the polymeric nanoparticles with ligands that allow the particles to dock at a specific site of the cell. In addition, polymeric systems allow for the cargo to be released in a controlled and stimuli‐responsive manner. The advantages that nanoparticulate delivery systems present in the treatment of respiratory diseases and infections are summarised in this review. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease
Magnetic resonance relaxation properties of superparamagnetic particles
Authors: Gossuin Yves , Gillis Pierre , Hocq Aline , Vuong Quoc L , Roch Alain
Published: March 2009

Nanometric crystals of maghemite are known to exhibit superparamagnetism. Because of the significance of their magnetic moment, maghemite nanoparticles are exceptional contrast agents and are used for magnetic resonance imaging (of the liver, spleen, lymph nodes), for magnetic resonance angiography and for molecular and cellular imaging. The relaxivity of these agents depends on their size, saturation magnetization and magnetic field and also on their degree of clustering. There are different types of maghemite particles whose relaxation characteristics are suited to a specific MRI application. The relaxation induced by maghemite particles is caused by the diffusion of water protons in the inhomogeneous field surrounding the particles. This is well described by a theoretical model that takes magnetite crystal anisotropy and Néel relaxation into account. Another type of superparamagnetic compound is ferritin, the iron‐storing protein: it contains a superparamagnetic ferrihydrite core. Even if the resulting magnetic moment of ferritin is far smaller than for magnetite nanoparticles, its massive presence in different organs darkens T2‐weighted MR images, allowing the noninvasive estimation of iron content, thanks to MRI. The relaxation induced by ferritin in aqueous solutions has been demonstrated to be caused by the exchange of protons between bulk water protons and the surface of the ferrihydrite crystal. However, in vivo, the relaxation properties of ferritin are still unexplained, probably because of protein clustering. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
The collapse of the fisheries sector in Kyrgyzstan: An analysis of its roots and its prospects for revival
Authors: Thorpe Andy , van Anrooy Raymon , Niyazov Bisheke N. , Sarieva Mairam K. , Valbo-Jørgensen John , Millar Andres Mena
Published: March 2009

The disintegration of the Soviet Union had profound economic and social effects on many of the newly independent transition economies. Nowhere was this more so than in the fisheries sector — with one of the biggest production shortfalls occurring in Kyrgyzstan, following the collapse of lake capture and pond-culture production. In 2005, aggregate landings were just 48 tonnes — barely 3 per cent of the catch level recorded in 1989. This article has two objectives. First it analyses the extent to which the dissolution of the Soviet Union can explain the collapse of the fisheries sector in Kyrgyzstan. Second, in the light of these findings, it considers what practical steps, if any, might be taken to revitalize the sector.