bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of benzo[c][2,7]naphthyridines
Authors: Nutaitis Charles F. , Marsh Stephen R.
Published: March 2009

A divergent synthesis of substituted benzo[c][2,7]naphthyridines 5a‐h is described, which features an intramolecular pyridyne cyclization step as the key reaction. The pyridyne precursors are conveniently prepared from the pyridinium hydrochloride 2 and the requisite anilines. Cyclization of the non‐symmetric substrates 3e and 3f did not proceed with significant regioselectivity.
Synthesis, purification and spectroscopic characterization of potential impurities of hexamethylmelamine
Authors: Talebian Abdolhassen , Ghiorghis Alem , Hammer Charles F. , Murril Evelyn A. , Pallas Frank
Published: March 2009

The syntheses and spectroscopic properties (ir, 1H nmr, 13C nmr, uv and ms) of pure samples of 2‐chloro‐4,6‐bis(dimethylamino)‐s‐triazine 1, 4,6‐dichloro‐2‐dimethylamino‐s‐triazine 2, 4,6‐bis(dimethylamino)‐s‐triazin‐2(lH)‐one 3, 4‐chloro‐6‐dimethylamino‐s‐triazin‐2(1H)‐one 4, 6‐dimethylamino‐s‐triazine‐2,4(1H,3H)‐dione 5, and 2,4,6‐tris(dimethylamino)‐s‐triazine (altretamine, HMM) are reported. Evidence for enol‐keto equilibria are also presented for 3, in which the enol form exhibits as an H‐bonded dimer structure similar to the dimer of organic carboxylic acids.
A new synthetic route to 1,3,4‐oxadiazoles. Pharmacological study of some new derivatives
Authors: Reynaud Pierre , El Hamad Youssef , Davrinche Catherine , Nguyen‐Tri‐Xuong Emmanuel , Tran Gilles , Rinjard Pierre
Published: March 2009

2‐Substituted 1,3,4‐oxadiazoles have been examined as possible prodrugs of antidepressant hydrazides. A new method of synthesis of this heterocycle from thionoester and five new oxadiazoles substituted at the 2‐position by a 4‐pyridyl or 4‐aminophenyl group and at the 5‐position by a phenyl group are described.
Synthesis of new 3‐(phenoxyphenyl)sydnones marija Šindler‐kulyk
Authors: Jakopčić Krešimir , Mance Ana Dunja
Published: March 2009

The title compounds were prepared by dehydrocyclization of corresponding substituted N‐nitrosoglycines obtained from isomeric o‐, m‐ and p‐aminodiphenyl ether with ethyl bromoacetate and subsequent nitrosation of the intermediate N‐arylsubstituted glycines.
Synthesis of 1,2‐diazepino[3,4‐b]quinoxalines and pyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4‐b]quinoxalines via a 1,3‐dipolar cycloaddition reaction
Authors: Kurasawa Yoshihisa , Kureyama Tomomi , Yoshishiba Noriko , Katoh Ritsuko , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The reaction of 6‐chloro‐2‐(1‐methylhydrazino)quinoxaline 4‐oxide 8 with furfural, 3‐methyl‐2‐thiophene‐carbaldehyde, 2‐pyrrolecarbaldehyde, 4‐pyridinecarbaldehyde and pyridoxal hydrochloride gave 6‐chloro‐2‐[2‐(2‐furylmethylene)‐1‐methylhydrazino]quinoxaline 4‐oxide 5a, 6‐chloro‐2‐[1‐methyl‐2‐(3‐methyl‐2‐thienyl‐methylene)hydrazino]quinoxaline 4‐oxide 5b, 6‐chloro‐2‐[1‐methyl‐2‐(2‐pyrrolylmethylene)hydrazino]quinoxa‐line 4‐oxide 5c, 6‐chloro‐2‐[1‐methyl‐2‐(4‐pyridylmethylene)hydrazino]quinoxaline 4‐oxide 5d and 6‐chloro‐2‐[2‐(3‐hydroxy‐5‐hydroxymethyl‐2‐methyl‐4‐pyridylmethylene)‐1‐methylhydrazino]quinoxalme 4‐oxide 5e, respectively. The reaction of compound 5a or 5b with 2‐chloroacrylonitrile afforded 8‐chloro‐3‐(2‐furyl)‐4‐hydroxy‐1‐methyl‐2,3‐dihydro‐1H‐1,2‐diazepino[3,4‐b]quinoxaline‐5‐carbonitrile 6a or 8‐chloro‐4‐hydroxy‐1‐methyl‐3‐(3‐methyl‐2‐thienyl)‐2,3‐dihydro‐1H‐1,2‐diazepino[3,4‐b]quinoxaline‐5‐carbonitrile 6b, respectively, while the reaction of compound 5e with 2‐chloroacrylonitrile furnished 11‐chloro‐7,13‐dihydro‐4‐hydroxy‐methyl‐5,14‐methano‐1,7‐dimethyl‐16‐oxopyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4‐b]quinoxaline 7.
A convenient synthesis of cis‐4‐(sulfomethyl)‐piperidine‐2‐carboxylic acid: NMR assignment
Authors: El Hadri Ahmed , Leclerc GÉRard
Published: March 2009

cis‐4‐(Sulfomethyl)piperidine‐2‐carboxylic acid was obtained in 22% overall yield from 4‐(hydroxymethyl)‐pyridine via the o‐silyl N‐oxide and trimethylsilylcyanide. The cis configuration of 5 was unambiguously assigned by 200 MHz 1H nmr and cosy experiments.
A facile synthesis of enol type acyl cyanides via a 1,3‐dipolar cycloaddition reaction and a cyano group migration
Authors: Kurasawa Yoshihisa , Kureyama Tomomi , Yoshishiba Noriko , Okano Tomoko , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The reaction of 7‐chlorotetrazolo[1,5‐a]quinoxaline 5‐oxide 4a or 7‐chloro‐1,2,4‐triazolo[4,3‐a]quinoxaline 5‐oxide 4b with 2‐chloroacrylonitrile gave 7‐chloro‐4‐(2‐cyano‐2‐hydroxyvinyl)tetrazolo[1,5‐a]quinoxaline 5a or 7‐chloro‐4‐(2‐cyano‐2‐hydroxyvinyl)‐1,2,4‐triazolo[4,3‐a]quinoxaline 5b, respectively. Alcoholysis of compound 5a or 5b afforded 7‐chloro‐4‐ethoxycarbonylmethylene‐4,5‐dihydrotetrazolo[1,5‐a]quinoxaline 6a or 7‐chloro‐4‐ethoxycarbonylmethylene‐4,5‐dihydro‐1,2,4‐triazolo[4,3‐a]quinoxaline 6b, respectively. Compounds 5a,b were found to exist as a syn and anti mixture of the enol form, while compounds 6a,b occurred as the enamine and methylene imine forms. The tautoraeric character and/or D‐H exchange of the vinyl protons are described for compounds 5a,b and 6a,b.
A new class of laser dyes from acridinedione derivatives
Authors: Shanmugasundaram Palanisamy , Prabahar K. Joseph , Ramakrishnan Vayalakkavoor T.
Published: March 2009

Synthesis of 10‐aryl‐3,4,6,7,9,10‐hexahydro‐1,8(2H,5H)‐acridinedione as a new class of laser dyes is reported. These dyes lase around 475–495 nm and are compared to the standard dye coumarin 102.
Synthesis of 1‐(4‐substituted)benzyl‐6‐hydroxyisoquinolines with potential activity on NA+,K+‐atpase
Authors: Cerri Alberto , Mauri Paola , Mauro Marina , Melloni Piero
Published: March 2009

The synthesis of 1‐(4‐substituted)benzyl‐6‐hydroxyisoquinolines, to be evaluated in the displacement of the specific 3H‐ouabain binding to Na+,K+‐ATPase, is described. The key step involved a cyclization to the isoquinoline ring under Pictet‐Gams conditions which was best performed with the 6‐hydroxy group protected as the benzyl ether. When an unsaturated ester group was present in position 4 of the 1‐benzyl group, this was best introduced before the cyclization step, since the IIeck reaction on 1‐(4‐bromobenzyl)‐6‐hydroxyisoquinoline (8) with acrylic acid derivatives was not successful in all cases.
Aerial oxidation kinetics of a phenolic porphyrin in acid solution
Authors: Milgrom Lionel R. , Hill Jonathan P.
Published: March 2009

The rate of aerial oxidation of the title porphyrin (1) in dichloromethane (DCM), acidified with trifluoro‐acetic acid (TFA), was found to be first‐order in 1 and second‐order in TFA at low TFA concentrations, and second‐order in both 1 and TFA at higher TFA concentrations. At the lower TFA concentrations, aerial oxidation gives the two‐electron oxidised product 2, while at the higher TFA concentrations, a porphyrin pication radical 3 is formed. These results are rationalised by a kinetic scheme requiring, (i), preequilibrium involving transient formation of a porphyrin tetracation 4, (ii), two‐electron oxidation of 4 to a diprotonated oxidised porphyrin 5, (iii) reaction of 5 with solvent water and (iv), conproportionation of 5 with 1 to generate 3.
Synthesis of (r)‐ and (s)‐1‐formyl‐6,7,8,9‐tetrahydro‐ N,N‐(dipropyl)‐3H‐benz[e]indol‐8‐amines: Potent and orally active 5‐ht1a receptor agonists
Authors: Lin Chiu‐Hong , Ennis Michael D. , Hoffman Robert L. , Phillips Gillian , Haadsma‐Svensson Susanne R. , Ghazal Nabil B. , Chidester Connie G.
Published: March 2009

An efficient synthesis of the potent and orally active 5‐HT1A agonists, (R)‐(+)‐ and (S)‐(‐)‐1‐formyl‐6,7,8,9‐tetrahydro‐N,N‐dipropyl‐3H‐benz[e]indol‐8‐amines 1a and 1b, is described. This synthesis was accomplished in twelve steps from commercially available 1,5,6,7‐tetrahydro‐4H‐indol‐4‐one (5). The key step involved a regio‐controlled Friedel‐Crafts acylation of 1‐(p‐toluenesulfonyl)indol‐4‐acetyl chloride with ethylene to yield a versatile synthon, 3‐(p‐toluenesulfonyl)‐6,7,8,9‐tetrahydro‐3H‐benz[e]indol‐8‐one (10). Subsequent coupling of this ketone with chiral α‐methylbenzylamine under reductive amination conditions yielded a mixture of diastereomers. These diastereomers were efficiently separated by either chromatography or fractional recrystallization of the derived hydrochloride salts. Debenzylation of the pure diastereomers was followed by alkylation and formylation to yield (R)‐(+)‐ and (S)‐(‐)‐enantiomers 1a and 1b with >99% purity.
Chemistry of thienopyridines. XLII. Three novel compounds derived from thienopyridine N‐oxides
Authors: Klemm L. H. , Muchiri Daniel R. , Anderson Mark , Salbador William , Ford John
Published: March 2009

Extension of the Reissert‐Henze reaction to treatment of thieno[2,3‐b]pyridine 7‐oxide with potassium thiocyanate and benzoyl chloride in water‐methylene chloride gives a 2% yield of bis(6‐thieno[2,3‐b]pyridyl) disulfide. Peroxidation of 5‐ethylthieno[2,3‐b]pyridine (4) forms the 7‐oxide 5 (53%), converted to a monopicrate 5a. Picrate 5a undergoes N‐deoxygenation to 4‐picrate on drying at 78° in vacuo, but shows the expected additive mass spectrum of 5 (thermally stable) and picric acid. Nucleophilic displacement of chloride ion from 7‐chlorothieno[3,2‐b]pyridine (derived, in turn, from thieno[3,2‐b]pyridine 4‐oxide) by the anion from ethyl cyanoacetate gives 7‐(1‐cyano‐1‐ethoxycarbonyl)methylene‐4,7‐dihydrothieno[3,2‐b]pyridine (82%), stable in this iminodienic tautomeric form.
Studies on isocyanides and related compounds. A convenient synthesis of 2,3‐disubstituted spiroimidazolones
Authors: Bossio Ricardo , Marcaccini Stefano , Papaleo Sandro , Pepino Roberto
Published: March 2009

The four‐component condensation between cycloketones 1, ammonium formate, and isocyanides 2 afforded formamides 3, which were dehydrated to the corresponding isocyanides 4. Upon treatment with n‐butyllithium, compounds 4 cyclized to spiroimidazolones 6, via the carbanions 5. A series of 2,3‐disubstituted spiroimidazolones 8 was obtained by reacting 5 with aldehydes 7.
On the bromination of thieno[c]‐fused 1,5‐naphthyridines and their isomeric N‐oxides using dibromoisocyanuric acid in fuming sulfuric acid
Authors: Malm Johan , Hörnfeldt Anna‐Britta , Gronowitz Salo
Published: March 2009

Thieno[2,3‐c]‐1,5‐naphthyridine (3), thieno[2,3‐c]1,5‐naphthyridine 5‐oxide (7), thieno[3,2‐c]‐1,5‐naphthyridine (5) and thieno[3,2‐c]‐1,5‐naphthyridine 5‐oxide (9) could conveniently be brominated at room temperature using dibromoisocyanuric acid in fuming sulfuric acid. Bromination occurred in good to moderate yields at the β position in the thiophene ring. Thieno[2,3‐c]‐1,5‐naphthyridine 9‐oxide (12) and thieno[3,2‐c]‐1,5‐naphthyridine 9‐oxide (13) also gave substitution in the thiophene ring at 95°. It was also found that 12 was deoxygenated under these reaction conditions. Direct oxidation of the brominated thieno[c]naphthyridines with m‐chloroperbenzoic acid gave the 5‐oxides in high yield.
Praziquantel analogs. Synthesis of substituted 4‐(2‐,3‐ and 4‐R)‐carboxyphenyl‐1,4‐pyrazin‐2‐ones
Authors: Martínez Roberto , Rubio Manuel F. , Toscano Ruben A. , Villalobos Xochitl , Brito Marco A.
Published: March 2009

The title compounds have been synthesized in a one step reaction by condensation between 2‐piperazinone with substituted benzoic acids.
Reactions of 2,3‐dihydro‐1H‐cyclohepta[b]pyrazines with acyl halides
Authors: Kawamata Yuuki , Imafuku Kimiaki , Li Dong‐Hao , Jin Zhong‐Tian , Li Zhi‐Hong , Xiao Yan‐Wen
Published: March 2009

2 When3‐dihydro‐1H‐cyclohepta[b]pyrazine (3) was treated with acetyl chloride under the Friedel‐Crafts conditions, its pyrazine ring opened to afford 2‐[N'‐acetyl‐(2‐aminoethyl)amino]tropone. Reactions with propionyl and butyryl chloride also gave similarly ring‐opened products. On the other hand, aromatic benzoyl chlorides reacted with compound 3 to afford N‐benzoyl‐substituted 2,3‐dihydro‐1H‐cyclohepta[b]pyrazines, in addition to ring‐opened compounds.
Synthesis and Properties of a selenium‐bridged bisquinolone
Authors: Löwe Werner , Schmidt Robert
Published: March 2009

The preparation of the selenium‐bridged bisquinolone 5 has been investigated. Compound 5 was methylated giving the N‐methyl derivative 6. Compound 5 and phosphorus oxychloride yielded 4‐chloroquinoline 8 which was converted to novel selenium heterocycles 7, 11 and 12 and the 4‐phenoxy product 9.
Ring opening reaction of the pyridinium salt of 4‐nitro‐3‐isoxazolin‐5‐one: A preparation of trifunctionalized methane derivatives
Authors: Nishiwaki Nagatoshi , Takada Yuji , Inoue Yoji , Tohda Yasuo , Ariga Masahiro
Published: March 2009

The ring cleavage of the pyridinium salt of 4‐nitro‐3‐isoxazolin‐5‐one 1 was found to proceed under mild basic conditions and to give cyano‐aci‐nitroacetates 2 in quantitative yields. The ring opened products 2 have three different functional groups at the same carbon atom, and are worth applying as a useful building block to syntheses of polyfunctionalized compounds.
A study of some isopropenyl‐substituted dihydrofuro[1]benzopyranones
Authors: Yamaguchi Seiji , Saitoh Akihito , Kawase Yoshiyuki
Published: March 2009

A pyrone‐ring formation using N,N‐dimethylacetamide dimethyl acetal in refluxing xylene converted some o‐hydroxyacetophenone derivatives 1a‐e to the corresponding dihydrofuro[1]benzopyranones 2a‐e.
Synthesis of 1,4‐benzodiazepine‐1‐carbothioamides, bicyclic analogues of the TIBO‐type anti‐HIV agents
Authors: Liu Jie , Dodd Robert H.
Published: March 2009

A series of N'‐substituted 1,4‐benzodiazepine‐1‐carbothioamides 2a‐j were prepared by reacting the precursor 1,4‐benzodiazepine 11 with the corresponding N‐substituted isothiocyanates 2a‐i or with sodium thiocyanate‐trifluoroacetic acid (2j). Despite the structural ressemblance of these molecules with the potent TIBO‐type anti‐HIV compound R82150, 2a‐j displayed no anti‐HIV activity in vitro.
Comparative reactivity of 3‐methyl‐5‐phenylisoxazole and 3‐methyl‐5‐phenylisothiazole against electrophilic compounds
Authors: Alberola Angel , Calvo Luis , Rodríguez Rodríguez Ma Teresa , Sañudo Ma Carmen
Published: March 2009

A comparative study of reactions of 3‐methyl‐5‐phenylisoxazole and 3‐methyl‐5‐phenylisothiazole with electrophilic compounds in the presence of n‐BuLi, LICA or LICA‐TMEDA is reported. By using LICA‐TMEDA, regioselective reactions of the heterocyclic compounds at the C‐3 methyl group are obtained. With n‐BuLi or LICA and the isoxazole derivative a product mixture at the C‐4 position and the C‐3 methyl group is found. In the case of isothiazole compound, only with methyl iodide and n‐BuLi, the dialkylated product at both positions is formed.
Substituent effects on the tautomer ratios between the enamine and methylene imine forms in side‐chained quinoxalines
Authors: Kurasawa Yoshihisa , Miyashita Ryuichiro , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The p‐ and m‐substituted 3‐arylcarbamoylmethylene‐2‐oxo‐1,2,3,4‐tetrahydroquinoxalines 3a‐o showed the tautomeric equilibria between the enamine C and methylene imine D forms in dimethyl sulfoxide or dimethyl sulfoxide/trifluoroacetic acid media. The linear correlation of the Hammett σp and σm values with the log KT values was observed in the dimethyl sulfoxide/trifluoroacetic acid (2:1) media of compounds 3a‐o, wherein KT meaned the tautomeric equilibrium constants ([D]/[C]).
Syntheses of various 5‐(bromoaryl)‐substituted uracils
Authors: Wellmar Ulf , Hörnfeldt Anna‐Britta , Gronowitz Salo
Published: March 2009

The Suzuki Pd(0)‐catalyzed coupling between arylboronic acids and aryl bromides or iodides in weakly alkaline medium, previously further developed by us, has been used for regioselective preparation of 5‐(2′‐bromo‐5′‐furyl)‐, 5‐(2′‐bromo‐4′‐furyl)‐, 5‐(2′‐bromo‐5′‐thienyl)‐, 5‐(2′‐bromo‐4′‐thienyl)‐, 5‐(4′‐bromo‐2′‐thiazolyl)‐, 5‐(3′‐bromophenyl)‐, 5‐(6′‐bromo‐2′‐pyridyl)‐ and 5‐(4′‐bromo‐2′‐pyrimidyl)‐substituted 2,4‐di‐t‐butoxypyrimidines. In the coupling between 2,4‐di‐t‐butoxy‐5‐pyrimidineboronic acid and the nine different aryl dibromides that were tried as coupling partners, only the 2,4‐ and 2,5‐dibromothiazoles did not give satisfactory yields, 15% and 0%, respectively. The other seven aryl dibromides gave the desired 5‐(bromoaryl)‐2,4‐di‐t‐butoxypyrimidines in 58‐89% yield. Attempts to synthesise 2,4‐di‐t‐butoxy‐5‐(2′‐bromo‐4′‐thienyl)pyrimidine from 2‐bromo‐4‐iodothiophene failed. Dealkylation of the 5‐(bromoaryl)‐2,4‐di‐t‐butoxypyrimidines in 2.5 M hydrochloric acid gave the corresponding 5‐(bromoaryl)uracils in almost quantitative yields.
Rearrangements of substituted 3‐azidoazetidines: Unexpected formation of a substituted oxazole
Authors: Marchand Alan P. , Rajagopal D. , Bott Simon G.
Published: March 2009

Thermolysis of neat N‐carboethoxy‐3‐azido‐3‐ethylazetidine (3) at 200° under argon produced the corresponding cyclic imine 4 (68% yield). Prolonged refluxing of a mixture of N‐triflylazetidin‐3‐one (7), sodium azide, and titanium tetrachloride in acetonitrile solvent afforded recovered 7 (25% yield) along with a colorless microcrystalline solid, 8, mp 104–105° (20% yield), whose structure was established unequivocally via application of X‐ray crystallographic methods.
Synthesis and in vitro anti‐human cytomegalovirus (hcmv) activity of certain alkenyl substituted cytosines and 5‐halocytosines
Authors: Lewis Arthur F. , Revankar Ganapathi R. , Rando Robert F.
Published: March 2009

The 1‐[(Z)‐2‐penten‐1‐yl] and 1‐(3‐methyl‐2‐buten‐1‐yl) derivatives of cytosine, 5‐bromocytosine, 5‐fluorocytosine, and 5‐iodocytosine were prepared by a reaction of the sodium salt of the requisite cytosine with (Z)‐1‐bromo‐2‐pentene and 4‐bromo‐2‐methyl‐2‐butene, respectively. The eight alkenylcytosines 5a‐5h were evaluated in cell culture for their anti‐HCMV activity. Only the derivatives of 5‐bromocytosine, 5c and 5d, showed slight activity in this assay.
Preparation of fused 1,3‐oxazine‐2,4‐diones as potential antitumor agents
Authors: Player Mark R. , Walter Sowell J.
Published: March 2009

A series of indole, thiophene and pyrrole‐fused 1,3‐oxazine‐2,4‐diones, 2‐methyl‐1,3‐oxazin‐4‐ones and 2‐dimethylamino‐1,3‐oxazin‐4‐ones were synthesized and evaluated as antitumor agents.
Synthesis and spectroscopic characterizations of both 1‐ethyl‐4,8‐dihydro‐10‐methoxy‐3‐methyl‐8‐r1‐6‐r2‐dipyrazolo[3,4‐b:4′,3′‐f]‐[1,5]diazocin‐5(1H)‐ones and 1‐ethyl‐1,4,8,9‐tetrahydro‐3,9‐dimethyl‐8‐r1‐6‐r2‐dipyrazolo[3,4‐b:4′,3′‐f][1,5]diazocine‐5,10‐diones of pharmaceutical interest
Authors: Migliara Onofrio , Lamartina Liliana , Rainieri Rosina
Published: March 2009

The non‐selective methylation of compounds 3a‐d using ethereal diazomethane, allowed the synthesis of isomers 4 and 5 which were useful intermediates for the preparation, by a simple approach, of the title compounds 7 and 9. A complete assignment of the chemical shifts to the carbon atoms of the compounds 7 and 9 was performed by different nmr experiments, such as DEPT and XHDEPT for onebond CH correlations and COLOC experiments for long‐range C‐H correlations.
Temperature dependence of 13c nmr spectra of 9‐methylaminoacridinium and 4‐methylaminopyridinium perchlorate
Authors: Kalatzis Evangelos
Published: March 2009

The double bond character of the exocyclic carbonnitrogen bond of 9‐methylaminoacridinium ion is less than that of 4‐methylaminopyridinium ion since the energy barrier of rotation around this bond is lower by 8 kJ mol−1 in the case of the 9‐methylaminoacridinium ion.
Application of the ortho‐lithiation‐cyclization strategy to N‐benzyl‐and N‐phenethylamine derivatives
Authors: Lete Esther , Collado M. Isabel , Sotomayor Nuria , Vicente Teresa , Villa MarÍA‐JesÚS
Published: March 2009

The ortho‐lithiation‐cyclization of iodinated N,N‐diacylphenethylamines provides a convenient method for the preparation of 2‐(2‐acetoamidoethyl)acetophenones and 2‐(2‐benzamidoethyl)benzophenones, which could be easily transformed into dihydroisoquinolines. By contrast, the N‐ethylamino, N‐acetylamino, and N‐trimethylsilylamino moieties studied as ortho‐directing groups provide poor assistance to the metalation of N‐benzyl‐ and N‐phenemylamines and the corresponding isoindolone or isoquinolone derivatives are obtained in low yields.
Dipyrryl ketones from dipyrrylmethanes
Authors: Thyrann Thomas , Lightner David A.
Published: March 2009

Dipyrrylmethanes are smoothly and efficiently oxidized to dipyrryl ketones by ceric ammonium nitrate in water‐tetrahydrofuran‐acetic acid solvent at room temperature.
Heteroannulation of naphthoquinones. Studies on the reaction of 2‐bromo‐2,3‐dihydronaphthoquinone derivatives with 1,2‐binucleophiles.
Authors: Couladouros Elias A. , Plyta Zoi F. , Iliadis Theodoros , Roussis Vassilios , Papageorgiou Vassilios P.
Published: March 2009

Heterocyclic derivatives of naphthoquinones were synthesized via their 2‐bromo‐2,3‐dehydro‐intermediates. This new route may lead to the formation of benzo[a]phenothiazin‐5‐ones, benzo[f]quinoxalin‐6‐ones as well as their 1,4 (or 7,10) dihydroxy‐derivatives in high yields. The possible mechanisms involved in the formation of these compounds are discussed.
New pyrazole‐annulated azathioxanthenes as potential intercalators: Synthesis and structure elucidation
Authors: Varvaresou A. , Tsotinis A. , Siatra‐Papastaikoudi Th. , Calogeropoulou T.
Published: March 2009

As part of our program aiming at developing efficacious intercalating agents, a new series of pyrazole‐annulated azathioxanthenes 15a‐e has been synthesized. Structure elucidation of 15a‐e was based on their spectral data and especially the NOESY nmr spectrum of analog 15a.
A quantitative study of substituent effects on oxidative cyclization of some 2‐methylsubstituted aldehydes. Thiosemicarbazones induced by ferric chloride
Authors: Noto Renato , Meo Paolo Lo , Gruttadauria Michelangelo , Werber Giuseppe
Published: March 2009

In order to gain further mechanistical information about the cyclization of thiosemicarbazones and thiosemicarbazone‐type substrates induced by metallic salts as oxidizing agents, we performed the synthesis of substrates 1a‐s and a kinetic study of the oxidative cyclization of 1 to 5‐imino‐Δ2‐1,3,4‐thiadiazole 2 and 1,2,4‐triazoline‐5‐thione 3 derivatives induced by methanolic ferric chloride solutions. The results of cyclization were compared to those of corresponding semicarbazones. The kinetic data were analyzed by means of the Hammett's equation and ρ values discussed.
Fluorescence studies of some 1,2,3‐triazolo[1,5‐a]pyridine and imidazo[1,2‐a]pyridine esters and their vinylogues
Authors: Latham Elliot J. , Stanforth Stephen P.
Published: March 2009

The relative fluorescence intensity of a number of 1,2,3‐triazolo[1,5‐a]pyridine esters 6 and 7 and imidazo‐[1,2‐a]pyridine esters 10 and 11 were determined and compared with methyl imidazo[1,2‐a]pyridine‐5‐carboxylate 2 and 4‐methylumbelliferone 3.
Studies on pyrrolidinones. Catalyst induced selectivity during heterocyclizations of organosilicon compounds into 1,3,4‐oxadiazoles or 1,2,4‐triazines
Authors: Cauliez Pascal , Rigo BenoǏT , Fasseur D. , Couturier D.
Published: March 2009

Heterocyclizations of trisilylated diacylhydrazines derived from pyroglutamic acid occurs selectively and yields, depending on the conditions, either to 1,3,4‐oxadiazoles (basic catalyst: fluoride anion) or to fused 1,2,4‐triazines (acidic catalyst: triflic acid).
Preparation and structure determination of 1‐benzyl‐, 1‐methyl‐ and 1H‐5‐[(2‐nitro‐2‐phenyl)ethenyl]imidazoles
Authors: Aulaskari Paula , Ahlgrén Markku , Rouvinen Juha , Vainiotalo Pirjo , Pohjala Esko , Vepsäläinen Jouko
Published: March 2009

1‐R‐5‐[(2‐Nitro‐2‐phenyl)ethenyl]imidazoles (R = Bn, Me, H) 6a,b,c were synthesized by the Knoevenagel reaction of the corresponding aldehydes 4a,b,c with phenylnitromethane 5. The E‐isomers 6a,b,c were precipitated from the reaction mixture as crystalline compounds in 89, 81 and 60% yields, respectively. Traces of the Z‐isomers 6a′b′,c′ were found in the reaction mixtures but could be obtained in a ratio of 4:3 from the E‐form with UV irradiation. The E‐forms were more stable and the Z‐isomers changed again to the E‐isomers in several weeks.
Reaction of 3‐hydroxy‐1,2,3,4‐tetrahydroquinoline‐2,4‐diones with ethyl(triphenylphosphoranylidene)acetate
Authors: Kafka Stanislav , Kovář Michal , Klásek Antonín , Kappe Thomas
Published: March 2009

The Wittig reaction of 3‐hydroxy‐1,2,3,4‐tetrahydroquinoline‐2,4‐diones 2 with ethyl (triphenyl‐phosphoranylidene)acetate 3 proceeds stereoselectively to give E‐4‐carbethoxymethylene‐1,2,3,4‐tetra‐hydro‐2‐quinolones 4, which were hydrolyzed to corresponding acids 6 Butenolides 5 were detected and, in some cases, isolated as a minor product of the Wittig reaction.
Syntheses of 2‐(2‐arylethyl)imidazoles
Authors: Shafiee A. , Rastkary N. , Foroumadi A.
Published: March 2009

Condensation of 2‐methylimidazole with arylaldehyde 4 and subsequent reduction of the intermediate 5 with Raney‐nickel gave 2‐[2‐(2,4‐dichlorophenyl)ethyl]imidazole 2. Compound 11 was prepared from compound 10 similarly. Reaction of compound 2 with methylsulfonyl chloride gave 1‐methylsulfonyl‐2‐[2‐(2,4‐dichlorophenyl)ethyl]imidazole (7a) in moderate yield. Nitration of compound 11 (Ar = 3‐pyridyl) gave the desired nitro compounds 14 and 15.
Ring closure and rearrangement reactions of 4‐azido‐2‐oxoquinoline‐3‐carboxylates and 4‐azidocoumarin‐3‐carboxylates
Authors: Stadlbauer Wolfgang , Prattes Susanne , Fiala Werner
Published: March 2009

4‐Azido‐2‐oxoquinoline‐3‐carboxylates and 4‐azidocoumarin‐3‐carboxylates 6, which were obtained from the corresponding 4‐hydroxy derivatives 1 via 4‐tosylates 2 or 4‐chloro compounds 4, cyclized upon thermolysis to 3‐alkoxyisoxazolo[4,3‐c]quinolin‐4(5H)‐ones or the corresponding coumarins 8, whereas at slightly higher temperatures a 3‐O, 4‐O‐rearrangement took place to give the 4‐alkoxy‐isoxazolo[4,3‐c]‐quinolin‐3‐ones and the corresponding coumarins 9. The necessary reaction conditions could be obtained easily with the help of differential scanning calorimetry.
Synthesis of 6,7‐dimethoxy‐1‐[(halophenoxy)‐methyl]‐1,2,3,4‐tetrahydroisoquinolines
Authors: Cho Su‐Dong , Kim Sung‐Kyu , Chung Hyun‐A , Kang Young‐Jin , Yoon Yong‐Jin
Published: March 2009

Some 6,7‐dimethoxy‐1‐[(halophenoxy)methyl]‐1,2,3,4‐tetrahydroisoquinolines were synthesized from N‐[2‐(3,4‐dimethoxyphenyl)ethyl]‐2‐chloroacetamide via three steps in good yield.
Synthesis of chiral azamacrocycles using the bis(α‐chloroacetamide)s derived from chiral 1,2‐diphenylethylenediamine
Authors: Hu Kejiang , Bradshaw Jerald S. , Dalley N. Kent , Xue Guoping , Izatt Reed M. , Krakowiak Krzysztof E.
Published: March 2009

Optically active diphenyl‐substituted tetraaza‐12‐crown‐4 diamide (10), tetraaza‐15‐crown‐5 diamide (12), tetraaza‐18‐crown‐6 diamide (11), and hexaaza‐18‐crown‐6 diamide (9) ligands were prepared by treating the appropriate secondary diamines with the (R,R)‐ and (S,S)‐ forms of 1,2‐bis(N‐methyl‐α‐chloracetamido)‐1,2‐diphenylethane (20). Macrocyclic diamides 9 and 10 were reduced to form the optically active diphenyl‐substituted hexaaza‐18‐crown‐6 (13) and tetraaza‐12‐crown‐4 (14), respectively. Reduction of macrocyclic diamide ligands 11 and 12 gave a complex mixture of products from which the desired tetraaza‐15‐crown‐5 and 18‐crown‐6 compounds could not be isolated. Dichloride 20 was prepared by treating the chiral forms of 1,2‐ diphenylethylenediamine with chloroacetic anhydride or chloroacetyl chloride. The crystal structures for the (R,R)‐form of dichloride 20 and the (S,S)‐forms of macrocycles 10 and 11 are reported.
Preparation of 2‐phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline and 2‐methyl‐4‐oxo‐3,4‐dihydroquinazoline derivatives formation
Authors: Hradil Pavel , Kvapil Lubomír , Hlaváč Jan , Weidlich TomáŠ , Lyčka Antonín , Lemr Karel
Published: March 2009

The cyclization of phenacyl anthranilate has been studied with the aim to develop the synthesis of 2‐(2′‐aminophenyl)‐4‐phenyloxazole. However, a different course of the reaction than expected was observed. 2‐Phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (3a) was formed by the reaction of phenacyl anthranilate (2) with ammonium acetate under various conditions.

3‐Hydroxy‐2‐phenyl‐4(1H)‐quinolinone (4) arose by heating compound 3a in acetic acid. The same compound was obtained by melting compound 3a, but the yield was lower.

Different types of products resulted in the reaction of compound 3a with acetic anhydride. Under mild conditions acetylated products 2‐acetoxymethyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (7a) and 2‐acetoxymethyl‐3‐acetyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (8) were prepared. If the reaction was carried out under reflux of the reaction mixture, molecular rearrangement took place to give cis and trans 2‐methyl‐4‐oxo‐3‐(1‐phenyl‐2‐acetoxy)vinyl‐3,4‐dihydroquinazolines (9a and 9b). All prepared compounds have been characterised by their 1H, 13C and 15N NMR spectra, IR spectra and MS.
The synthesis of new 2,4‐diaminofuro[2,3‐d]pyrimidines with 5‐biphenyl, phenoxyphenyl and tricyclic substitutions as dihydrofolate reductase inhibitors
Authors: Gangjee Aleem , Dubash Nauzer P. , Queener Sherry F.
Published: March 2009

Nonclassical 2,4‐diamino‐5‐substituted furo[2,3‐d]pyrimidines 4a‐i, 5a‐b and 7a‐f were synthesized as extended aromatic ring appended analogs of previously reported antifolates 1a‐b. The extended aromatic system was designed to better interact with a phenylalanine residue (Phe69) of dihydrofolate reductase from the opportunistic pathogen Pneumocystis carinii to afford potent and selective inhibitors of Pneumocystis carinii dihydrofolate reductase. The target compounds were synthesized by nucleophilic displacement of 2,4‐diamino‐5‐(chloromethyl)furo[2,3‐d]pyrimidine 3 with the appropriate aromatic amine or thiol. The compounds were evaluated as inhibitors of dihydrofolate reductase from Pneumocystis carinii and Toxoplasma gondii, and their selectivity was determined using rat liver dihydrofolate reductase as the mammalian reference. In the C8‐N9 bridged series, compound 4e, with a 3‐(2‐methoxydibenzofuran)‐ side chain, exhibited greatest potency and was more than 3 times as selective for Pneumocystis carinii dihydrofolate reductase compared to rat liver dihydrofolate reductase. Compounds 4b and 4c also exhibited selectivity. Compounds in the C8‐S9 bridged series showed comparable potencies, and each showed higher selectivity for Pneumocystis carinii dihydrofolate reductase compared to rat liver dihydrofolate reductase.
A versatile synthesis of 4,5‐dihydropyrrolo[1,2‐a]quinoxalines
Authors: Abonia Rodrigo , Insuasty Braulio , Quiroga Jairo , Kolshorn Heinz , Meier Herbert
Published: March 2009

The reaction of 1‐(2‐aminophenyl)pyrrole with aromatic or heteroaromatic aldehydes in ethanol and catalytic amounts of acetic acid leads to 4,5‐dihydropyrrolo[1,2‐a]quinoxalines in high yields. When aliphatic aldehydes were used under the same conditions, a slow oxidation to the corresponding pyrrolo[1,2‐a]quinoxalines can occur; the oxidation can be avoided by preparing in situ the 5‐acetyl derivatives of the 4,5‐dihydropyrrolo[1,2‐a]quinoxalines.
Synthesis and [3+2] cycloaddition reaction of 3‐[(trimethylsilylmethylamino)(methylthio)‐methylene]heterocyclic compounds
Authors: Tominaga Yoshinori , Takada Satoshi , Kohra Shinya , Shigemitsu Yasumitsu
Published: March 2009

3‐[(Trimethylsilylmethylamino)(methylthio)]methylene‐2‐coumaranone (4a) and 1‐methyloxindole (4b), readily prepared by reactions of the corresponding bis(methylthio)methylene heterocyclic compounds (2a, b), with (trimethylsilylmethyl)amine (3), were found to be synthetic equivalents of heterocyclic alkylidene‐azomethine ylides. Reactions of 4a, b with reactive heterodipolarophiles such as aldehydes and ketones and reactive alkenes in the presence of cesium fluoride gave the 1,3‐dipolar cycloadducts, 3‐(2‐oxazoli‐dinylidene)‐oxindole and ‐coumaran‐2‐one derivatives (8a‐j, 9a‐h), as well as pyrrolylidenecoumaran‐2‐one and oxindole derivatives (12‐15,17,18), via the 1,3‐elimination of (methylthio)trimethylsilane.
Triazolylbenzimidazolthiones and derivatives of the new 1,2,3‐triazolo[ 1,5‐a][ 1,3,5]benzotriazepine heterocycle
Authors: Biagi Giuliana , Giorgi Irene , Livi Oreste , Nardi Antonio , Scartoni Valerio
Published: March 2009

Four new triazolylbenzimidazolthione derivatives (2a‐d), analogous to triazolylbenzimidazolone derivatives previously tested as activators of the BKCa potassium channels, were prepared and assayed without success. Some derivatives of a new tricyclic nitrogen heterocycle, 1,2,3‐triazolo[1,5‐a][1,3,5]benzo‐triazepine, bearing a carboxamido group in the 3 position, other substituents in the 8 position and a carbonyl (5a‐d) or thione (6a‐c) or methylthio (7a‐c) function in the 5 position were synthesised. The nucleophilic displacement of the methylthio substituent with morpholine or cyclopentylamine provided the 5‐amino‐substituted tricyclic derivatives 8a‐d. Starting from the l‐(2‐nitrophenyl)‐4‐cyano‐5‐amino‐1,2,3‐triazole (9), the 3‐cyano‐triazolobenzotriazepin‐5‐one derivative 12 was also obtained. The majority of the new compounds were tested towards the BKCa potassium channels, the benzodiazepine and adenosine A1 and A2a receptors, but no remarkable activity was detected.
The psuedo‐michael reaction of 2‐aminoimidazolines 2. Part 1. Synthesis and structure assignment of isomeric 5(1H)‐Oxo and 7(1H)‐Oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates
Authors: Matosiuk Dariusz , Pihlaja Kalevi , Ovcharenko Vladimir V. , Dybała Izabela , Kozioł Anna E. , Gdaniec Maria , Szumiło Halina , Karczmarzyk Zbigniew
Published: March 2009

The pseudo‐Michael reaction of 1‐aryl‐2‐aminoimidazolines‐2 with diethyl ethoxymethylenemalonate (DEEM) was investigated. Extensive structural studies were performed to confirm the reaction course. For derivatives with N1 aromatic substituents, it was found that the reaction course was temperature dependent. When the reaction temperature was held at −10 °C only the formation of 1‐aryl‐7(1H)‐oxo‐2,3‐dihydroimi‐dazo[1,2‐a]pyrimidine‐6‐carboxylates (4) was observed in contrast to earlier suggestions. Under the room temperature conditions, the same reaction yielded mixtures, with varying ratio, of isomeric 1‐aryl‐7(1H)‐oxo‐ (4a‐4f) and 1‐aryl‐5(1H)‐oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates (5a‐5f). The molecular structure of selected isomers, 4b and 5c, was confirmed by X‐ray crystallography. Frontal chro‐matography with delivery from the edge was applied for the separation of the isomeric esters. The isomer ratio of the reaction products depended on the character of the substituents on the phenyl ring. The 1‐aryl‐7(1H)‐oxo‐carboxylates (4a‐4f) were preferably when the phenyl ring contained H, 4‐CH3, 4‐OCH3 and 3,4‐Cl2 substituents. Chloro substitution at either position 3 or 4 in the phenyl ring favored the formation of isomers 5a‐5f. The isomer ratios were confirmed both by 1H NMR and chromatography. The reaction of the respective hydrobromides of 1‐aryl‐2‐aminoimidazoline‐2 with DEEM, in the presence of triethylamine, gave selectively 5(1H)‐oxo‐esters (5a‐5f).
Structure analysis of some α‐(n‐methyl‐n‐formylaminomethyl)‐quinolines
Authors: Maślankiewicz Andrzej , Michalik Ewa , Kowalski Andrzej
Published: March 2009

The 1H and 13C nmr spectra of the rotational isomers 3a and 3b of 6‐N‐methyl‐N‐formylaminomefhyl)‐thioquinanthrene were completely assigned with a combination of 1D and 2D nmr techniques. The key‐parts of this methodology were long‐range proton‐carbon correlations and NOE experiments with N‐methyl‐N‐formylaminomethyl substituent. The X‐ray study of 4‐methyl‐2‐N‐methyl‐N‐formylaminomethyl)quinoline 4a as well as 1H and 13C nmr spectra show that N‐methyl‐N‐formylaminomethyl substituent in 4a and 4b has a different steric arrangement than the same substituent in 3a and 3b.
Characterization and identification of cleavage products of 3‐glycosyl‐5‐substituted‐2‐isoxazoline
Authors: Gelabert Laura I. , Fascio Mirta L. , D'Accorso Norma B.
Published: March 2009

We report herein the synthesis of new synthons obtained by reductive opening of 3‐glycosyl‐5‐substituted‐2‐isoxazolines. Different cleavage products have been obtained depending on the substituents (aliphatic or aromatic) in position five of the heterocycle ring. The new compounds are characterized physically and spectroscopically.
Influence of scale, stoichiometry and temperature on the synthesis of 2,8‐dihalo analogues of tröger's base from the corresponding anilines and paraformaldehyde
Authors: Jensen Jacob , Strozyk Michal , Warnmark Kenneth
Published: March 2009

The yields of 2,8‐dihalo analogues of Tröger's base in the condensation between 4‐haloanilines and paraformaldehyde was found to be highly sensitive to the crucial reaction parameters of scale, stoichiometry and temperature. The reaction conditions were optimized allowing for the semi‐large scale synthesis of the 2,8‐diiodo‐ (2) and 2,8‐dibromo‐ (3) analogues, respectively.
Reaction of tetraazathiapentalene and thiadiazolopyrimidine derivatives with heterocumulenes: Cycloaddition and elimination reactions via hypervalent sulfur intermediates
Authors: Matsumura Noboru , Ito Atsushi , Tomura Masaaki , Okumura Yasuyuki , Mizuno Kazuhiko
Published: March 2009

Tetraazathiapentalene derivative 1 reacts with heterocumulenes such as diphenylketene (2) and 2‐pyridylisothiocyanate (5) to give heterocycles 3, 6 and 7 with elimination of methylisothiocyanate. The reactions of thiadiazolopyrimidine derivatives 8a‐b with ethoxycarbonyl isothiocyanate (9) and carbon disulfide (11) gives heterocycles 10 and 12 via thermal decomposition of 1:1 cycloadducts C and D which have a hypervalent sulfur. The mechanistic and reactivity features of these reactions are described.
Synthesis and physicochemical characterization of fluorescent (E)‐2‐stilbenyloxyalkylthiouracils and isomer differentiation using EIMS
Authors: Wyrzykiewicz Elzbieta , Wendzonka Monika
Published: March 2009

Twelve new fluorescent (E)‐2‐stilbenyloxyalkylthiouracils and 6‐methyluracils 5a‐51 were prepared. EI induced mass spectral fragmentation of these compounds was investigated. Fragmentation pathways are proposed on the basis of accurate mass and metastable transition measurements. Correlation between the intensities of the M+ and the selected fragment ions of these compounds is discussed. The data obtained permit a distinction of the metamers. The 1H and 13C NMR spectra of these compounds were assigned unambiguously using a combination of heteronuclear (HETCOR) spectra and the chemical shifts. The data derived from these spectra can be used to differentiate the isomers.
Novel nucleophilic CC bond‐forming tele‐reaction of imidazole ring
Authors: Ohta Shunsaku , Sato Kentaro , Kawasaki Ikuo , Yamaguchi Yuko , Nishio Satoko , Yamashita Masayuki
Published: March 2009

Reaction of 2‐(1‐chloro‐2,2‐dimethylpropyl)‐1‐methyl‐1H‐irnidazoles with diethyl methylmalonate in the presence of NaH gave a normal SN product, 2‐[(1,1‐diethoxycarbonylethyl)‐2,2‐dimethylpropyl]‐1‐methyl‐1H‐imidazole (2a), and two tele‐reaction products, 5‐(1,1‐diethoxycarbonylethyl)‐1‐methyl‐2‐(2,2‐dimethylpropyl)‐1H‐imidazole (3a) and trans‐4,5‐di‐(1,1‐diethoxycarbonylethyl)‐4,5‐dihydro‐1‐methyl‐2‐(2,2‐dimethylpropyl)‐1H‐imidazole (4a) in 5, 17 and 70% yields, respectively. The scope and mechanism of this reaction are discussed.
Preparation of pyrrole and pyrrolidine derivatives of pyrimidine. 1‐(2‐pyrimidinyl)pyrrole ‐ an inhibitor of X. phaseoli and X. malvacearum
Authors: Becker Irwin
Published: March 2009

Pyrrole and pyrrolidine derivatives of pyrimidine were prepared in which the nitrogen atom of the pyrrole or pyrrolidine ring is bonded directly to the 2‐ or 4‐carbon atom of the pyrimidine ring. Pyrrole derivatives were prepared by the dry distillation of an intimate mixture of an aminopyrimidine with mucic acid and by the reaction of a chloropyrimidine with potassium pyrrole. Pyrrolidine derivatives were prepared by the reaction of a chloropyrimidine with pyrrolidine and, in a single instance, by the catalytic hydrogenation of a pyrimidinylpyrrole. At a concentration of 200 mcg/mL, 1‐(2‐pyrimidinyl)pyrrole inhibited two plant pathogenic bacteria — Xanthomanus phaseoli (pathogenic on the bean plant) and Xanthomanus malvacearum (pathogenic on the cotton plant).
Where genetics and pathology meet: mulibrey nanism
Authors: Hes Frederik J , Morreau Hans
Published: March 2009

Mulibrey nanism is a rare autosomal recessive disorder with prenatal onset growth retardation (nanism) and dysmorphic features, including a wide range of abnormalities, such as cardiac disease (pericardial constriction, myocardial hypertrophy and fibrosis) and anomalies of muscle, liver, brain and eye, resulting in the acronym ‘mulibrey’. This commentary summarizes recent analysis of the diverse pathologies seen in this syndrome and highlights the need for pathologists and geneticists to work together. Insights into the pathology of rare genetic syndromes may have important lessons for our understanding of much commoner conditions. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Human view dynamics—The NATO approach
Authors: Handley Holly A. H. , Smillie Robert J.
Published: March 2009

A methodology was established to use the data captured in the NATO Human View to populate a simulation model; this provides a dynamic instantiation of the Human View data. The Improved Performance Research Integration Tool (IMPRINT), provided by the U.S. Army Research Laboratory was used as the simulation environment. By creating the Human View Dynamics, the data captured in the static products can be evaluated through tradeoff analysis and performance criteria. The demonstrated interoperability of the Human View static products and the IMPRINT dynamic modeling capability resulted in a mapping between the two domains. Additionally, the capability of the Integrated Performance Modeling Environment (IPME) used by Canada and the United Kingdom as a simulation environment was reviewed. © 2009 Wiley Periodicals, Inc. Syst Eng
Laparoscopic Radical Nephrectomy for T2 Renal Cell Carcinoma
Authors: Ritchie Robert W. , Sullivan Mark E. , Jones Adam
Published: March 2009

Background:

Large volume centres from the USA suggest laparoscopic radical nephrectomy (LRN) for T2 (>7 cm) renal cell carcinoma (RCC) is safe and associated with few complications. Similar data for low and intermediate volume centres in Europe is lacking. Objective: To determine whether LRN for T2 RCC in two intermediate volume UK hospitals compares favourably with larger volume centres. To determine whether LRN for T2 RCC is associated with favourable outcomes when compared to LRN for T1 RCC.

Patients and methods:

Data from 118 consecutive LRN performed in Oxford, UK (tertiary academic centre, catchment population 2,000,000) and Reading, UK (large district general hospital, catchment population 500,000). All patients undergoing LRN from 2004 to 2008 were included; outcome data were collected prospectively. All patients underwent a standard 4-port trans-peritoneal LRN with intact specimen removal. Patients were divided into two groups—Group 1 (clinical T1 tumours) and Group 2 (clinical T2 tumours). Demographic data and operative outcome data were collected for every patient including age, weight, operative duration, estimated blood loss, transfusion rates, complications, hospital stay and histology. Data were compared using Chi-square test and the Student t-test.

Results:

Mean patient age was 62.5 years; 57% of tumours were right sided. Mean tumour dimension in Group 1 was 4.3cm and 9.3cm in Group 2. Demographics were similar between the two groups. Operative duration, estimated blood loss and transfusion rates were significantly greater in Group 2. Despite this, complication rates, conversion rates and hospital stay were similar. 12% of tumours were benign and nearly half of all clinical T2 tumours were ultimately staged T3 on final histology.

Conclusions:

LRN for T2 RCC can be performed safely in intermediate volume centres. The procedure is more challenging but operative outcomes are similar to LRN for smaller tumours. Many >7 cm RCC are T3 on final histology.
Ecomorphological selectivity among marine teleost fishes during the end-Cretaceous extinction
Authors: Friedman Matt
Published: March 2009

Despite the attention focused on mass extinction events in the fossil record, patterns of extinction in the dominant group of marine vertebrates—fishes—remain largely unexplored. Here, I demonstrate ecomorphological selectivity among marine teleost fishes during the end-Cretaceous extinction, based on a genus-level dataset that accounts for lineages predicted on the basis of phylogeny but not yet sampled in the fossil record. Two ecologically relevant anatomical features are considered: body size and jaw-closing lever ratio. Extinction intensity is higher for taxa with large body sizes and jaws consistent with speed (rather than force) transmission; resampling tests indicate that victims represent a nonrandom subset of taxa present in the final stage of the Cretaceous. Logistic regressions of the raw data reveal that this nonrandom distribution stems primarily from the larger body sizes of victims relative to survivors. Jaw mechanics are also a significant factor for most dataset partitions but are always less important than body size. When data are corrected for phylogenetic nonindependence, jaw mechanics show a significant correlation with extinction risk, but body size does not. Many modern large-bodied, predatory taxa currently suffering from overexploitation, such billfishes and tunas, first occur in the Paleocene, when they appear to have filled the functional space vacated by some extinction victims.
Phytophthora ramorum and Phytophthora kernoviae on naturally infected asymptomatic foliage
Authors: Denman S. , Kirk S. A. , Moralejo E. , Webber J. F.
Published: March 2009

Phytophthora ramorum and Phytophthora kernoviae are recently discovered invasive Phytophthoras causing leaf necrosis and shoot tip dieback mostly on ornamental and forest understorey species, but also cause bleeding cankers on stems of a wide range of tree species. Sporulation occurs only on infected shoots or fruits and foliage so foliar hosts are central to the disease epidemiology. In field trials to assess infection in trap plants exposed to natural inoculum of P. ramorum and P. kernoviae on rhododendron in south west England, it was discovered that leaves of the trap plants (Rhododendron‘Cunninghams White’) and holm oak (Quercus ilex) were asymptomatically infected and supported sporulation of both pathogens. More than half the rhododendron trap plants exposed to inoculum of P. kernoviae became infected compared with approximately a third of those exposed to P. ramorum in a natural situation. Approximately one third of the infections were detected from asymptomatic foliage for both pathogens. The significance of these findings for plant health regulation based on visual inspection as a measure to prevent introduction and dissemination of both these pathogens is explored and research gaps identified.