bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 5H‐benzoxazolo[3,2‐a]quinazolin‐5‐ones
Authors: Kim Dong Han
Published: May 2009

5H‐Benzoxazolo[3,2‐a]quinazolin‐5‐ones (Xa‐d) were synthesized in excellent yields from N‐(2‐hydroxyphenyl)anthranilic acids (Ia‐d) and cyanogen bromide. The synthesis was based on the mechanistic consideration of the reactions of salicylic acid with cyanogen bromide previously reported in the literature. A versatile alternative route to these novel heterocyclic compounds was through thermal cyclization of N‐(2‐benzoxazolyl)‐2‐fluorobenzamides (XIII) obtained by reacting 2‐fluorobenzoyl chloride with 2‐aminobenzoxazoles. The reaction of Xb with ethanol in the presence of potassium hydroxide gave an ethoxyquinazolinone (XVII). Similarly, the alkaline hydrolysis of Xb afforded an quinazolindione (XVIII).
Synthesis of nectriapyrone
Authors: Abramson Hanley N. , Wormser Henry C.
Published: May 2009

A totally synthetic route to the antibacterial fungal metabolite nectriapyrone (1) has been achieved by condensation of methylmalonyl dichloride with ethyl trans‐4‐methyl‐3‐oxo‐4‐hexenoate followed by hydrolysis, decarboxylation, and methylation of the resulting 3‐methyl‐4‐hydroxy‐5‐carbethoxy‐6‐(trans‐1‐methyl‐1‐propenyl)‐2‐pyrone. Exploration of an alternate scheme involving the dehydrogenation of 6‐substituted‐4‐methoxy‐5,6‐dihydro‐2‐pyrones, prepared by Reformatsky reaction of ethyl γ‐bromo‐β‐methoxycrotonate with various aldehydes, was abandoned since it did not appear to have general applicability to the preparation of nectriapyrone and its analogs.
Functionalization of substituted 2‐(1H)pyridones. I. A novel synthesis of a‐arylgyloxylates and related systems
Authors: Showalter H. D. Hollis , Haskell Theodore H.
Published: May 2009

A novel synthetic strategy is presented in which the heteroaryl[(trimethylsilyl)oxy]acetonitrile intermediate 3 is utilized either as a homologation or reverse‐polarity synthon for convenient entry into its corresponding α‐hydroxy‐ and α‐ketoarylalkanoate 4 and 6, respectively. Further functionalization, including a stereo‐selective oximation procedure, is described.
Synthesis ofN,N'‐Diacyl‐1,2‐di‐(4‐pyridyl)ethylenedianiines
Authors: Braña M. F. , Rodriguez Maria L. López , Garrido J. , Roldán C. M.
Published: May 2009

Reaction ofN‐(4‐pyridylmethyl)benzamideN‐oxides with acetic anhydride yielded dimerization compounds. This dimerization occurs at the atom attached to the pyridine ring. These compounds so obtained were evaluated for analgesic and antiinflammatory activity.
Pyrazolo[1,5‐d]triazines‐1,2,4. I. Dérivés pyrazoliques
Authors: Lancelot Jean‐Charles , Maume Daniel , Robba Max
Published: May 2009

La synthese d'intermédiaires pyrazoliques destinés à ětre mis en oeuvre dans des réactions de cyclisation ou de réarrangement menant à des pyrazolo[1,5‐d]triazines‐1,2,4 est décrite. Il s'agit de dérivés où le pyrazole est substitué en 5 par des groupements hydrazide ou hydrazone et éventuellement bromés en 4. Les (pyrazolyl‐5)‐2 oxadiazoles‐1,3,4 et thiadiazoles‐1,3,4 sont accessibles par cyclisation d'hydrazides pyrazoliques avec l'oxychlorure ou de décasulfure de phosphore. La formation de dihydro‐1,2 oxo‐1 (ou thioxo‐1) pyrazolo[1,5‐d]triazines‐1,2,4 est observée dans quelques cas. Les structures sont établies par rmn.
Unusual friedel‐crafts reactions. 3. Synthesis of 2,4‐Diethoxychromans and their conversion into benzopyrylium perchlorates
Authors: Bigi Franca , Casiraghi Giovanni , Casnati Giuseppe , Sartori Giovanni
Published: May 2009

By a coordinated reaction of phenols (I) and malonaldehyde‐bis‐(diethylacetal) (II) at ambient temperature, under unusual Friedel‐Crafts conditions, a class of new compounds, 2,4‐diethoxychromans (IV) has been synthesized. Subsequent treatment of IV in acetic acid with 70% perchloric acid produces 1‐benzopyrylium perchlorates (V).
Photochemical substitution reactions of 4‐Pyridinecarbonitrile with aliphatic alcohols in neutral and acidified medium
Authors: Carolina Tullio , Clerici Angelo , Coggiola Dianella , Morrocchi Sergio
Published: May 2009

Chemical evidence is given that the title photo‐reactions proceed via hydrogen abstraction by the photo‐excited base from the alcohol in neutral medium and via electron‐transfer process between the photo‐excited base and the alcohol in hydrochloric acid acidified medium.
Synthesis of 1‐aryl‐3‐trifluoromethyl‐5‐methylthio‐1,2,4‐triazoles from 2‐arylmethylisothiosemicarbazides and 1,1,1‐trichloro‐3,3,3‐trifluoroacetone
Authors: Pilgram Kurt H. , Skiles Richard D.
Published: May 2009

The reaction of 1,1,1‐trichloro‐3,3,3‐trifluoroacetone with S‐methyl‐2‐arylisothiosemicarbazides affords an unusual synthesis of 1‐aryl‐3‐trifluoromethyl‐5‐methylthio‐1,2,4‐triazoles from which 1‐aryl‐3‐trifluoromethyl‐1,2,4(4H)‐triazole‐5‐ones are obtained on treatment with base.
Synthesis and anticonvulsant activity of 3‐amino‐4(3H)‐quinazolinones
Authors: Kornet M. J. , Varia T. , Beaven W.
Published: May 2009

Several 3‐amino‐4(3H)‐quinazolinones were prepared from o‐aminobenzoylhydrazines and triethyl orthoformate or from isatoic anhydrides, hydrazines and triethyl orthoformate. o‐Aminobenzoylhydrazine intermediates were obtained by reaction of isatoic anhydrides with hydrazines. Some of the aminoquinazolinones displayed anticonvulsant activity in mice.
On triazoles. V. Synthesis of 1‐ and 2‐R1‐3‐R2,R3‐amino‐5‐amino‐1,2,4‐triazoles
Authors: Reiter JÓZsef , Pongó László , Somorai Tamás , Dvortsák PÉTer
Published: May 2009

The correct isomeric and tautomeric structure of different 1‐ and 2‐R1‐3‐R2,R3‐amino‐5‐amino‐1,2,4‐triazole derivatives prepared from the correspondingN‐cyano‐N'‐R2,R3‐S‐methyl‐isothioureas and the corresponding hydrazines was proved with the help of their ir, uv,1H‐nmr and13C‐nmr spectra as well as the uv spectra of the Schiff bases of an isomeric pair.
Chemical reactions of cycloalkanespirohydantoins. Part 2. Synthesis of new 4‐hydroxyimidazolidinone N3‐substituted from cycloalkanespirohydantoins
Authors: Salazar Loreto , Rubido Julia , Espada Modesta , Pedregal Carmen , Trigo Gregorio , Elguero José
Published: May 2009

N3‐Substituted hydantoins have been to undergo lithium aluminum hydride reduction (THF, room temperature, 5 hours) to give 4‐hydroxy‐2‐imidazolidinones in good yields.
Réductions chimique et électrochimique de benzopyranno‐1 as‐triazines
Authors: Bellec Christian , Vinot Nicole , Maitte Pierre
Published: May 2009

La réduction électrochimique des benzopyranno‐1‐(4,3‐e]‐as‐triazinones‐3 fournit un dérivé dihydrogéné‐1,4 qui se réarrange en dihydro‐4,4a, celui‐ci est réductible ultérieurement avec contraction de cycle et conduit aux benzopyrannoimidazolones. L'action des organomagnésiens sur les benzopyranno‐1 as‐triazines provoque la réduction en α du noyau aromatique (dihydro‐4,4a) tandis que la réduction électrochimique conduit, via les dihydro‐1,4, à des dérivés dihydrogénés en position‐1,10a. Les dihydro‐1,4 benzopyrannotriazines subissent également par réduction une contraction du cycle triazine, fournissant des benzopyrranoimidazoles. Les dihydro‐1,10a, selon qu'elles possèdent ou non le motif hydrazone, sont réduites en imidazoles ou conduisent aux dérivés tétrahydrogénés.
Preparation of reissert compounds derived from the thieno[3,2‐c]pyridine, thieno[2,3‐d]pyridazine and the thieno[2,3‐d]pyrimidine ring systems
Authors: New J. S. , Jass P. A. , Barrett K. A.
Published: May 2009

The use of tributyltin cyanide, trimethylsilyl cyanide and potassium cyanide in the Reissert reaction is contrasted in the furo[3,2‐c]pyridine, thieno[3,2‐c]pyridine, thieno[2,3‐dpyridazine, and thieno[2,3‐d]pyrimidine ring systems.
The reaction of ethyl chromone‐2‐carboxylates with 1,2‐diaminobenzene
Authors: Markees Diether G.
Published: May 2009

Ethyl chromone‐2‐carboxylate and all its benzoanalogs were prepared and caused to react with 1,2‐diami‐nobenzene to give 2‐(2‐hydroxybenzoyl)methinyl‐3‐oxo‐1,2,3,4‐tetrahydroquinoxaline and its benzo analogs. The condensation products of diethyl oxalate and methyl hydroxyaryl ketones which were required for the preparation of the starting esters, were found to be subject to ring chain tautomerism.
Synthesis and reactions of “biginelli‐compounds”. Part I
Authors: Kappe Christian Oliver , Roschger Peter
Published: May 2009

Various reactions of 2‐oxo(or thioxo)‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylic acid derivatives (Biginelli‐compounds) were investigated. The site of methylation and acylation on 6‐methyl‐4‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylic acid ethyl ester 1a and its 2‐oxo derivative 9a was studied. The synthesis of pyrimido[2,3‐b]thiazines and thiazolo[3,2‐a]pyrimidines was accomplished by condensation of 1a with 1,3‐and 1,2‐dielectrophiles. A Dimroth‐like rearrangement yielding 6H‐1,3‐thiazines can be observed when 1a was treated with dimethylformamide and phosphorus oxychloride. The formation of indeno[1,2‐d]pyrimidines can be achieved by intramolecular Friedl‐Crafts acylation of 9a and 13, respectively. Finally a route for the preparation of 4,6‐disubstituted‐pyrimidine‐5‐carbonitriles is presented, starting with Biginelli‐compound 25.
Oxazole ring cleavage in the course of the synthesis of heterocyclic azo dyes
Authors: Savarino P. , Viscardi G. , Carpignano R. , Barni E.
Published: May 2009

The formation of azo dyes by coupling the diazonium salts of aminophenyloxazolopyridines with N,N‐di‐ethylaniline was shown to be a suitable probe to check the stability of the oxazole ring in the course of their preparation. Depending on experimental conditions, “closed” and “opened” systems could be obtained separately.
Development of a new synthesis of 3‐(1H‐tetrazol‐5‐yl)‐4(3H)‐quinazolinone, sodium salt via an amidine intermediate
Authors: Vinogradoff Anna P. , Peet Norton P.
Published: May 2009

A new synthesis of the recently reported 3‐(1H‐tetrazol‐5‐yl)‐4(3H)‐quinazolinone, sodium salt (1, MDL‐427), an experimental mediator release inhibitor, was developed from: (1) reaction of 5‐aminotetrazole 3 and triethyl orthoformate 6 to give ethyl N‐(1H‐tetrazol‐5‐yl)formimidate 8, (2) reaction of methyl anthranilate and imidate 8 to give amidine 11, and (3) treatment of 11 with base to give 1. Investigation of each of these steps independently led to a significantly more efficient, facile and higher‐yielding 1‐pot process. A brief examination of anthranilic acid 13 and its salts and derivatives 14 to 17 in this process found them to have dissimilar reactivities. The formation of amidine 11 as an isolable intermediate was unusual, as was its failure to cyclize under standard neutral or acidic conditions. The absolute requirement for base to effect cyclization of 11 appears to be unprecedented.
Heterocyclic variants of the 1,5‐benzodiazepine system. V. Derivatives of 2‐(ortho‐R1‐anilino)‐4‐(p‐R2‐phenyl)‐3H‐1,5‐benzodiazepines
Authors: Conés Eduardo , Martínez Roberto , Ceballos Irma
Published: May 2009

Mono‐N‐methylation of 2‐(ortho‐R1‐anilino)‐4‐(p‐R2‐phenyl)‐3H‐1,5‐benzodiazepines IV is achieved in moderate yield with sodium hydride in methyl iodide. Reaction of the N‐methyl derivatives I with methoxyacetyl chloride gave the compounds II and III. The structure of all products was confirmed by ir, 1H‐nmr and mass spectrometry.
Reduction of n‐(1,3‐dioxolan‐2‐yl)‐1‐methylpyridinium ions: Molecular structure of the 4‐(l,3‐dioxolan‐2‐yl)‐1‐methyl‐1,2,3,6‐tetrahydropyridine‐borane complex
Authors: Rodriguez J. G. , Martinez‐Lopez N. , De Lerma J. Lopez , Perales A.
Published: May 2009

The reduction of the n‐(1,3‐dioxolan‐2‐yl)‐1‐methylpyridinium ions with sodium borohydride has been studied to prepare N‐methylformylpiperidines. Deuterium oxide was used as the solvent in order to assign the protons in the nmr spectra. As a product of the reaction, the 4‐(1,3‐dioxolan‐2‐yl)‐1‐methyl‐1,2,3,6‐tetrahy‐dropyridine‐borane complex, was isolated and crystallized. A X‐ray study of this borane complex has been carried out.
A lithiation approach to cordycepin analogues variously substituted at the C‐8 position
Authors: Hayakawa Hiroyuki , Tanaka Hiromichi , Sasaki Keiko , Haraguchi Kazuhiro , Saitoh Takafumi , Takai Fumi , Miyasaka Tadashi
Published: May 2009

Several 8‐substituted cordycepins were prepared via LDA lithiation of 2′,5′‐bis‐O‐(t‐butyldimethylsilyl)‐cordycepin and successive reactions of its C‐8 lithiated species with various types of electrophiles. Wittig reaction of the 8‐formyl derivative was also examined.
The synthesis of monomethoxy‐6‐methyl‐7H‐indeno[2,1‐c]quinolines
Authors: Quraishi Mumtaz A.
Published: May 2009

A series of monomethoxy‐6‐methyl‐7H‐indeno[2,1‐c]quinolines has been prepared by cyclization of the appropriate 1,3‐dioxoindan‐2‐yl‐ethylideneanilines, followed by Wolff‐Kishner reduction.
A synthetic entry into the quino[2,1‐b][1,3]benzoxazine ring system
Authors: Aversa M. C. , Bonaccorsi P. , Giannetto P.
Published: May 2009

The double ring closure of N‐(2‐hydroxybenzyl)anthranilic acids 1 with acetic anhydride or its acyclic analogous (RCH2CO)2O 2b and 2e lead to the formation of novel 12H‐quino[2,1‐b][1,3]benzoxazin‐5‐ones. The structure of the obtained compounds was proved with the use of their ir, mass, 1H and 13C nmr spectra. Homo‐ and heteronuclear two‐dimensional nmr experiments were performed to unambiguously assign all proton and carbon chemical shifts.
1,3‐Dipolar cycloaddition of nitrile oxides to N‐vinylcarbazole: Regioselective formation of 5‐(9‐carbazolyl)‐Δ2‐isoxazolines
Authors: Rao K. Rama , Nageswar Y. V. D. , Sattur P. B.
Published: May 2009

Aryl substituted nitrile oxides undergo 3 + 2 cycloaddition to N‐vinyl carbazole to afford only one regioisomer, i.e., 3‐aryl substituted 5‐(9‐carbazolyl)‐Δ2‐isoxazolines III in good yield.
Synthesis of new arylbenzofurodiazepin‐6‐ones
Authors: Viti Giovanni , Giannotti Danilo , Nannicini Rossano , Ricci Renzo , Pestellini Vittorio
Published: May 2009

Two new tetracyclic structures, containing the diazepine ring, were synthesized: 5,6‐dihydro‐12H‐benzofuro[3,2‐b][1,5]benzodiazepin‐6‐one and 5,6‐dihydro‐12H‐benzofuro[3,2‐b]pyrido[3,2‐f][1,5]diazepin‐6‐one. Thus N‐(2‐haloaryl)‐2‐[(2‐cyanophenyl)oxy]acetamides were cyclized to the corresponding N‐(2‐haloaryl)‐3‐amino‐2‐benzofurancarboxamides and then, through the formation of the central diazepine ring, to the title compounds. Formation of the diazepine ring took place only when an electron‐withdrawing group was present in the molecule to facilitate the nucleophilic attack of an amine in the benzofuran intermediate.
Isoindole derivatives from o‐diacylbenzenes and aromatic amines
Authors: Nan'ya Seiko , Fujii Takashi , Butsugan Yasuo
Published: May 2009

o‐Acetylbenzophenone produced yellow 1,2‐diaryl‐3‐(aryliminomethyl)isoindole by the reaction with aromatic amines in the absence of acid. On the reaction of o‐diacetylbenzene under the similar condition, three types of yellow products were obtained. The structures of these isoindole derivatives were determined and their formation mechanism was proposed.
Double 1,3‐dipolar cycloadditions of meso‐ionic heterocycles to N‐substituted maleimides
Authors: Nan'ya Seiko , Kurachi Yoshinori , Butsugan Yasuo
Published: May 2009

Double 1,3‐dipolar cycloadditions of 2,4‐diphenyl‐3‐methyloxazotium 5‐oxide and 3‐phenylsydnone to two molecules of N‐substituted maleimide afforded one or two isomeric 4,8‐iminobenzo[1,2‐c:4,5‐c′]dipyrrole‐1,3,5,7‐tetrone derivatives owing to the types of heterocycles as well as N‐substituents of maleimides.
Synthesis, crystal structure determination and pharmacological activity of 7,8,3′,4′‐tetramethoxyisoflavone
Authors: Domínguez Esther , Lete Esther , Villa María‐Jesús , Igartua Amaia , Sotomayor Nuria , Arrieta Juan M. , Berisa Agustin , Labeaga Luis , Orjales Aurelio , Germain Gabriel , Nastopoulos Vassilios
Published: May 2009

7 The8,3′,4′‐tetramethoxyisoflavone2was synthesized and its structure confirmed by X‐ray crystallographic analysis. Pharmacological screening was carried out with this compound in order to assess its pharmacological profile. Isoflavone2possessed antiinflamatory activity in the carrageenan oedema test, with a dose‐effect relationship comparable to that of hydroxylated flavonoids. It is noteworthy that2is one of the few isoflavones efficient as antiinflammatory with complete alkylation of hydroxyl groups.
Synthesis of novel indolizine derivatives
Authors: Bonnaud Bernard , Bigg Dennis , Patoiseau Jean‐François
Published: May 2009

The reaction of a number of γ‐butyrolactones with azole anions is shown to give γ‐substituted butanoic acids in moderate to good yields. The pyrrolyl and indolylbutanoic acids obtained underwent cyclization in a simple one‐pot procedure employing ethyl chloroformate and boron trifluoride etherate. Some aspects of the chemistry of the resulting indolizin‐8‐ones are described.
Diels‐alder reaction of (E)‐4‐(2‐nitroethenyl)‐1H‐imidazoles and methyl (E)‐3‐(1‐imidazol‐4‐yl)propenoates
Authors: Kosaka Keigo , Maruyama Kazumi , Nakamura Haruko , Ikeda Masazumi
Published: May 2009

Diels‐Alder reaction of methyl (E)‐3‐(1H‐imidazol‐4‐yl)propenoates 2, 3a‐c and (E)4‐(2‐nitroethenyl)‐1H‐imidazoles 3d,e with 2,3‐dimethyl‐1,3‐butadiene, cyclopentadiene, and cyclohexa‐1,3‐diene gave the corresponding cycloadducts 6–9.
Synthesis of 7‐ethyl‐4,7‐dihydro‐4‐oxo‐2‐(4‐pyridinyl)thieno[2,3‐b]pyridine‐5‐carboxylic acid
Authors: Bacon Edward R. , Daum Sol J.
Published: May 2009

7‐Ethyl‐4,7‐dihydro‐4‐oxo‐2‐(4‐pyridinyl)thieno[2,3‐b]pyridine‐5‐carboxylic acid (4), an analog of nalidixic acid, was synthesized in seven steps starting from commercially available 4‐methylpyridine. Bacterial susceptibility to compound 4 was tested and the title compound was found to exhibit only weak antibacterial activity against a variety of pathogens including S. Aureus, E. Coli and P. Aeruginosa.
The structure of β‐heteroaryl‐α,β‐dehydro‐α‐amino acid derivatives, intermediates in the synthesis of fused pyran‐2‐ones. Substituted methyl (Z)‐2‐benzoylamino‐3‐(5‐oxopyrazolinyl‐4)propenoates
Authors: Stanovnik Branko , Golič Ljubo , Kmecl Primož , Ornik Brina , Svete Jurij , Tišler Miha
Published: May 2009

It was shown by some chemical transformations that β‐heteroaryl‐α,β‐dehydro‐α‐amino acid derivatives 3 and 7, obtained from pyrazolone derivatives 1 or 6 and 2, exist in Z‐forms. The structure of 7 was confirmed by X‐ray analysis.
Hydroxyindole intermediates in the process of melanogenesis: A mass spectrometric study
Authors: Costa Carlo , Bertazzo Antonella , Allegri Graziella , Catinella Silvia , Traldi Pietro
Published: May 2009

Studies on the enzymatic formation of polymers from hydroxyindoles are described.

FAB analysis of the reaction mixtures followed by collisional spectroscopy of the most abundant ionic species was applied to analyze products obtained from the reaction catalyzed by tyrosinase on 4‐ or 5‐hydroxyindole at different times.

Results suggest that moieties of the precursors are still present in the oligomeric systems. Among the reaction products dimeric and trimeric compounds were detected by Fast Atom Bombardment and their structure assignment was achieved by collision spectroscopy.
The base‐promoted dehydration of rac.‐trans‐tetrahydro‐6‐hydroxy‐4‐[(2‐(dimethylamino)ethyl]‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(2H)‐one
Authors: Mohacsi Erno , O'Brien Jay P.
Published: May 2009

The base‐catalyzed alkylation of rac.‐trans‐tetrahydro‐6‐hydroxy‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(2H)‐one (1) with dimethylaminoethyl chloride in dimethyl sulfoxide provided predominantly rac.‐trans‐tetrahydro‐6‐hydroxy‐4‐[(2‐dimethylamino)ethyl]‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(2H)‐one (2) and in addition, 2,3‐dihydro‐4‐[2‐(dimethylamino)‐ethyl]‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(4H)‐one (3). A plausible mechanism is postulated for the dehydration of the rac.‐trans‐amide 2.
Synthesis of pyrazole analogues of isoaptazepine
Authors: Massa Silvio , Artico Marino , Mai Antonello , Mancuso Antonella , Corelli Federico
Published: May 2009

The synthesis of the novel tetracyclic rings 5 and 6 is described starting from 4‐cyano‐1‐methyl‐5(1H‐pyrrol‐1‐yl)‐1H‐pyrazole and its 3‐(1H‐pyrrol‐1‐yl)‐ isomer, respectively. The pathway employed is based on a one‐pot double annelation reaction involving the transformation of 13 into the required tetracyclic derivative 16. Lithium aluminum hydride/sulfuric acid reduction of the last compound furnished 5. A similar way was used for the synthesis of 6 by cyclization of 20.
The reformatsky reaction of 1‐acyl‐3,5‐dimethylpyrazoles. A convenient preparation of 4‐amino‐3‐oxoalkanoic acid derivatives
Authors: Kashima Choji , Kita Isanobu , Takahashi Katsumi , Hosomi Akira
Published: May 2009

The conversion of N‐acylpyrazoles into β‐keto esters was accomplished efficiently by the treatment with α‐bromo esters and zinc dust. Using this Reformatsky reaction of N‐acylpyrazoles, 4‐(protected amino)‐3‐oxoalkanoic acid derivatives were conveniently prepared as the key intermediates in the synthesis of statines.
Haloacetylated enol ethers: 3. Synthesis of 3,3a,4,5,6,7‐hexahydro‐3‐halomethylbenzoisoxazoles
Authors: Martins Marcos A. P. , Flores Alex F. C. , Freitag RogŔRio , Zanatta Nilo
Published: May 2009

The investigation of the halomethyl group effect on the regiochemistry of the reaction of 2‐acetylcyclo‐hexanones 1a‐d and β‐methoxyvinyl trifluoro methyl ketone derivative 2a with hydroxylamine to afford 3,3a,4,5,6,7‐hexahydro‐3‐halomethyl‐3‐hydroxy[2,1]benzoisoxazoles 3a‐c, and the respective dehydrated compounds 4a‐c, is reported. Compounds 1a‐c, 2a proved to be versatile building blocks for the regiospecific synthesis of isoxazole derivatives having a 3‐halomethyl substituent, in good yields.
Synthesis of 3‐dialkylaminomethyl‐5‐methyl‐4‐substituted‐1H‐pyrazoles. Selective functionalization of one methyl group via n‐nitration of 3,5‐dimethyl‐4‐substituted‐1H‐pyrazoles
Authors: Lammers H. , Vollinga R. , Zandbergen P. , Cohen‐Fernandes P. , Habraken C. L.
Published: May 2009

Treatment of 4‐substituted 3,5‐dimethyl‐1‐nitro‐1H‐pyrazoles 1 and 10a‐c with secondary amines in acetonitrile, in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), affords the novel dialkyl‐aminomethyl‐1H‐pyrazoles 5, 6, 7, 8, 11a‐c, 12a‐c and 13a‐c in good to excellent yields. In this way one of the, in general, inert methyl groups of 3,5‐dimethyl‐4‐substituted‐1H‐pyrazoles is functionalized creating a new synthetic route to azoles containing a coordinating substituent.
Polychlorination of thiophene. A reinvestigation
Authors: Temciuc Marcel , Hörnfeldt Anna‐Britta , Gronowitz Salo
Published: May 2009

Some old controversies in the literature with regard to the structures of trichlorothiophenes have been elucidated. In the course of these studies, we found that the best method for the preparation of 2,3,5‐trichlorothiophene is the direct chlorination of thiophene in the presence of catalytic amounts of ferric chloride. If 2,5‐dichlorothiophene is available 2,3,5‐trichlorothiophene can also be obtained in good yields through chlorination with thionyl chloride and sulfuryl chloride, using aluminum trichloride as catalyst.
Studies on intramolecular nh‐bridging in aromatic compounds. Part 3 [1–3]
Authors: Horaguchi Takaaki , Klemm L. H. , Norris Eric S.
Published: May 2009

A study was made of the use of calcium oxide as a catalyst at a temperature of 400–700° for the dehy‐drocyclization of four primary arylamines: 2‐aminobiphenyl, 1‐aminotriphenylene (5c), 2‐phenoxyaniline, and N‐(2‐aminophenyl)pyrrole. Maximal yields of cyclized products isolated were 53% (carbazole), 52% (4H‐naphtho[1,4‐def]carbazole), 18% (phenoxazine), and 0%, respectively. Comparison is made with reported cyclizations of the corresponding nitro and azido starting materials. In one case, treatment of I‐nitrotriphenylene with triethyl phosphite produced mainly diethyl N‐(1‐triphenylenyl)phosphoramidate (51%). Mono‐ and hemihydrochlorides of 5c are described. A mechanism for the catalyzed dehydrocy‐clization is proposed.
Regioselective synthesis of 6‐alkylated lumazine derivatives
Authors: Igarashi Mamoru , Tada Masaru
Published: May 2009

The regiospecific synthesis of alkylated lumazines is achieved by hetero Diels‐Alder addition between an oxadiazinone 2 and enamine. The reactions proceed stepwise by cycloaddition, decarboxylation and deamination to produce the 6‐alkylated lumazines.
On the metalation of 4‐substituted pyridazines
Authors: Turck Alain , Plé Nelly , Mojovic Ljubica , Ndzi Bruno , Quéguiner Guy , Haider Norbert , Schuller Herbert , Heinisch Gottfried
Published: May 2009

A series of new pyridazines bearing ortho‐directing groups at C‐4 (protected/activated amino or carboxylic acid functionalities) was prepared and their metalation with lithium 2,2,6,6‐tetramethylpiperidide was studied. Reactions of the ortho‐lithiated species thus obtained with aldehydes as electrophiles opens an access to 4,5‐disubstituted pyridazines 3, 4, 14, and 15.
The synthesis and transformations of ethyl (Z)‐2‐[2,2‐bis(ethoxycarbonyl)vinyl]amino‐3‐dimethylaminopropenoate, a new reagent in the synthesis of heterocyclic compounds
Authors: Soršak Gorazd , Sinur Amalija , Golič Ljubo , Stanovnik Branko
Published: May 2009

Ethyl (Z)‐2‐[2,2‐bis(ethoxycarbonyl)vinyl]amino‐3‐dimethylaminopropenoate (5), a new reagent in the synthesis of heteroaryl substituted β‐amino‐ α,β‐ ‐dehydro—amino acid derivatives and some fused hetero‐cyclic systems, was prepared from ethyl N‐2,2‐bis(ethoxycarbonyl)vinylglycinate (3) and N,N‐dimethyl‐formamide dimethyl acetal (4). The substitution of the dimethylamino group in the compound 5 with heterocyclic amines produced ethyl 2‐[2,2‐bis(ethoxycarbonyl)vinyl]amino‐3‐heteroarylaminopropenoates 7a‐f and, in some instances, [2,2‐bis‐(ethoxycarbonyl)vinyl]aminoazolo‐ or ‐azinopyrimidine derivatives 8g‐k.
Synthesis of fused purinoquinazolines. Three new heterocyclic ring systems
Authors: Da Settimo Antonio , Primofiore Giampaolo , Cristina Bertacchi Maria , Da Settimo Federico , Marini Anna Maria
Published: May 2009

The Ullmann reaction of 8‐aminotheophylline or 8‐aminocaffeine with 2‐chlorobenzoic acid and of 8‐bromotheophylline with ethyl‐2‐aminobenzoate afforded derivatives of three new heterocyclic systems: purino[7,8‐α]quinazoline‐5,9,11(6H,8H,10H)‐trione, purino[8,9‐b]quinazoline‐2,4,11(1H,3H,5H)‐trione and purino[8,7‐b]quinazoline‐2,4,6(1H,3H,11H)‐trione, respectively.
Synthesis and reactivity of 2,6‐diamino‐4‐methyl‐3‐pyridinecarbonitrile
Authors: Katritzky Alan R. , Rachwal Stanislaw , Smith Terrance P. , Steel Peter J.
Published: May 2009

2,6‐Dihydroxy‐4‐methyl‐3‐pyridinecarbonitrile is converted via its 2,6‐dichloro analog into the corresponding 2‐amino‐6‐chloro, 2‐chloro‐6‐amino, and 2,6‐diamino derivatives. The last reacts with benzene‐sulfonyl chloride to yield a tris‐sulfonyl derivative, the structure of which is demonstrated by X‐ray analysis.
Synthesis of 3‐aminorhodanine derivatives as aldose reductase inhibitors
Authors: Hanefeld Wolfgang , Schlitzer Martin
Published: May 2009

A number of 5‐condensated 3‐acylaminorhodanines3was prepared as potential inhibitors of the aldose reductase by acylation of the amino group of 3‐aminorhodanine1and subsequent condensation of the 5‐methylene function with appropriate aldehydes. Some of these compounds displayed interesting activity.
Heterocyclic variants of 1,5‐Benzodiazepine system. VII. Synthesis of substituted 2a‐Phenyl‐4‐methylsulfonyl‐2‐methoxy‐1,2,2a,3‐tetrahydroazeto[1,2‐a][1,5]benzodiazepin‐1‐ones
Authors: Martínez Roberto , Hernández Paulina E. , Angeles Enrique
Published: May 2009

The preparation of novel 2a‐phenyl‐4‐methylsulfonyl‐2‐methoxy‐1,2,2a,3‐tetrahydroazeto[1,2‐a][1,5]‐benzodiazepin‐1‐ones is described. The structure of all the products was corroborated by ir, mass spectrometry and 1H and 13C‐nmr.
Condensation reactions of 3‐Amino‐4‐imino‐4H‐thieno‐[3,4‐c][1]benzopyran
Authors: Nyiondi‐Bonguen E. , Sopbué Fondjo E. , Fomum Z. Tanee , Döpp Dietrich
Published: May 2009

The title compound 1 reacts with trifluoroacetic anhydride to give the doubly trifluoracetylated derivative 2 and in addition the coumarin derivative 3. In refluxing DMF, two moles of 1 react with loss of one molecule of ammonia to afford 4, which undergoes subsequent N‐acylation by β‐dicarbonyl compounds 9a‐f to yield N‐acyl derivatives 10a‐f. With dimethyl malonate (9a) besides compound 10a, the cycloacylated compound 11 was also obtained in good yield. Compound 11 is readily hydrolysed and decarboxylated with both acid and alkali to the previously described fused derivative 12. The latter may be converted into the new thienopyrimidinone derivative by action of aqueous alkali.
Synthesis and reactions of some 4‐heteroaryl‐3‐nitrocoumarins—
Authors: Govori S. , Rapic V. , Led O. , Čačić M. , Tabaković I.
Published: May 2009

By the action of 2‐aminothiazole, 2‐aminopyridines, and 2‐aminopyrimidines, respectively, on 4‐chloro‐3‐nitrocoumarin (3) the corresponding 4‐heteroarylamino‐3‐nitrocoumarins 5–7 have been isolated in very good yields. Reactions of coumarins 6 and 7 with either aqueous tetrabutylammonium bisulfate/sodium hydroxide in a two phase system or 5% aqueous sodium hydroxide have been studied.
A facile conversion of ethoxydihydropyrans to 4‐cyanoethylisoxazoles
Authors: Yamauchi M. , Akiyama S. , Watanabe T. , Okamura K. , Date T.
Published: May 2009

The reaction of ethoxydihydropyrans 2, which were prepared from 2‐methylene‐1,3‐dicarbonyl compounds 1 with ethyl vinyl ether, and hydroxylamine hydrochloride gave 4‐cyanoethylisoxazoles 3 whose substituents at the 3 and 5 positions were transformed from substituent at the 2 position and the acyl group of 2 regioselectively.
Friedländer reaction of 3‐acetyltropolones: Synthesis of naphthyridinyl‐ and allied heterocyclic‐substituted tropolones
Authors: Piao Ming‐Zhu , Imafuku Kimiaki
Published: May 2009

Five 3‐acetyltropolones reacted with 2‐amino‐3‐pyridinecarbaldehyde to afford the corresponding 3‐(1,8‐naphthyridin‐2‐yl)tropolones in excellent yields. In a similar manner, 1,6‐naphthyridin‐2‐yl‐,1,7‐naphthyridin‐2‐yl‐, 6‐pyrido[2,3‐b]pyrazinyl‐, and 1‐methyl‐6‐pyrazolo[5,4‐b]pyridyl‐substituted tropolones were prepared. Reactivities of amino‐substituted heteroarenecarbaldehydes in these reactions and properties of the products are also discussed.
Synthesis and stereochemical assignment of 7‐arylidene and 7‐heteroarylidene morphinan‐6‐ones
Authors: Nan Yang , Upadhyaya Subhash P. , Xu Wei , Hughes Kathrine E. , Dunn William J. , Bauer Ludwig , Bhargava Hemendra N. , Doss George A.
Published: May 2009

A number of (E)‐7‐arylidenenaltrexones were synthesized by azeotropic distillation of water from a benzene solution of naltrexone and an aromatic aldehyde (benzaldehyde, 4‐chloro‐ and 4‐fluorobenzaldehyde, 3‐and 4‐pyridinecarboxaldehyde and 1‐methyl‐2‐imidazolecarboxaldehyde) using piperidine as a catalyst. In addition, (E)‐7‐benzylidenenaloxone was prepared by the previously published Claisen‐Schmidt condensation using sodium hydroxide in methanol. The stereochemistry of these arylidene derivatives 3–9 was determined to be (E) by means of nuclear Overhauser enhancement experiments. The 13C nmr spectra of (E)‐3–9 are recorded in deuteriochloroform and those of the hydrochlorides in deuteriodimethyl sulfoxide.
Synthesis of pyrimidines from 3‐trifluoromethylsulfonyl‐oxypropeniminium triflates and nitriles; molecular and crystal structure of the 1:1 and 1:2 Adducts of a 4‐(2‐diethylaminovinyl)pyrimidine with triflic acid
Authors: Rahm Rainer , Maas Gerhard
Published: May 2009

The 3‐trifluoromethylsulfonyloxy‐1‐hexeniminium triflate 1 reacts with two equivalents of an aliphatic nitrile or of benzonitrile to give the 4‐(2‐diethylaminovinyl)pyrimidinediium bis(triflates) 4, which can be deprotonated to give the monoprotonated or neutral pyrimidines 5 and 6, respectively. When the related 1‐phenyl‐substituted iminium salt 7 is heated in acetonitrile at 140°, 1,5‐cyclization of the cation leading to indane derivative 8 competes with formation of the pyrimidinium salt 9. X‐ray crystal structure determination reveals significant differences in the bond lengths of mono‐and diprotonated 4‐(2‐diethylaminovinyl)pyrimidines 5a and 4a.
Study on the preparation of heteroaryl substituted enamines. A simple synthesis of heteroaryl substituted acetaldoximes from enamines
Authors: Antončopar  , Stanovnik Branko , Tišler Miha
Published: May 2009

A comparative study of the reactivity of methyl groups towards N, N‐dimethylformamide dimethyl acetal and tert‐butoxybis(dimethylamino)methane was carried out on methyl substituted six‐membered nitrogen containing heterocycles 1 to give enamines 2, which were easily transformed to oximes by treating with hydroxylamine hydrochloride in methanol. Most of them were isolated as (E, Z)‐oximes of heteroarylacetaldehyde (11), but 5‐(1,2,4‐triazinyl) substituted derivatives as (E, Z)‐oximes of 2,5‐dihydro‐1,2,4‐triazin‐(Z)‐5‐ylideneacetaldehyde (11t, 11u, and 12). Oximes were finally transformed to the corresponding acetonitriles 16 and 3‐(dimethylamino)acrylonitriles 17.
A convenient synthesis of 4‐trifluoromethyl‐4H‐[1,5,2]dioxazines and 4‐trifluoromethyl‐6H‐[1,2,5]oxadiazines
Authors: Kamitori Yasuhiro
Published: May 2009

1,1,1‐Trifluoroalkane‐2,3‐dione 3‐oximes 1 easily obtainable from aldehyde dimethylhydrazones were reacted with several aldehydes and ketones in the presence of acetic acid to afford 4‐trifluoromethyl‐4H‐[1,5,2]dioxadines 3 in satisfactory yields. When the reaction was carried out in the presence of ammonium acetate, 4‐trifluoromethyl‐6H‐[1,2,5]oxadiazines were obtained in good yields.
8‐Methyl‐7‐substituted‐1,6‐naphthyridine‐3‐carboxylic acids as New 6‐desfluoroquinolone antibacterials
Authors: Sabatini Stefano , Cecchetti Violetta , Tabarrini Oriana , Fravolini Arnaldo
Published: May 2009

1,6‐Naphthyridine‐8‐methyl‐7‐substituted‐3‐carboxylic acids were synthesized as new 6‐desfluoro‐quinolone antibacterials in which the usual fluorine atom at C‐6 position was replaced by an endocyclic nitrogen atom. Comparing the antibacterial activity of these 6‐azaquinolones with our previous 6‐amino and 6‐hydrogen counterparts, they resulted always less active. However, the presence of methyl group at C‐8 position ensure good Gram‐positive antibacterial activity, with minimum inhibitory concentrations values on the same order of ciprofloxacin for piperidinyl derivative 3d and tetrahydroisoquinolinyl derivative 3c.
Syntheses and reactions of 2,2′‐bisbenzimidazole systems
Authors: Von Glahn Benita , Kramer Walter , Neidlein Richard , Suschitzky Hans
Published: May 2009

Nucleophilic reactions of two 2,2′‐bisbenzimidazole systems, namely the bis(2H‐benzimidazole‐2‐ylidene) 2 and the dispiro[2H‐benzimidazole‐2,1′‐cyclohexane‐4′,2″‐2″H‐benzimidazole] 3, as well as the syntheses of new 2,2′‐bisbenzimidazoles are reported and their conversion into other heterocycles is described.
Thioamide derivatives of cannabinoids. A study of the influence of the thioamide function on regiochemistry in the synthesis of thioamide cannabinoids from 2,4‐dihydroxybenzothioamides
Authors: Sośnicki Jacek , Jagodziński Tadeusz , Królikowska Miroslawa
Published: May 2009

Several thiocarbamoyl derivatives of cannabinoids were obtained in the collidine‐catalysed condensation of 2,4‐dihydroxybenzothioamides with citral and citronellal. The thioamide function was found to change the regioselective preferences of the reaction as compared with the known cannabinoid syntheses from hydroxyacetophenones. The experimental results and theoretical (FMO theory) considerations made it possible to advance the reaction mechanism. Convenient methods were developed for the synthesis of the starting 2,4‐dihydroxybenzothioamides from resorcinol and isothiocyanates in the presence of the boron trifluoride/acetic acid 1:2 complex or aluminum chloride in nitromethane.
Synthesis of oxidized 1,2,3‐thiadiazines by hydroperoxy‐induced ring enlargement of 2‐benzenesulfonylaminoisothiazolium salts
Authors: Kolberg Arne , Sieler Joachim , Schulze Bärbel
Published: May 2009

Oxidation of 2‐benzenesulfonylaminoisothiazolium salts 1, 2 and their imines 3, 4 with hydrogen peroxide gave 1,2,3‐thiadiazine 1‐oxides 5, 6, which were converted into the corresponding 1,2,3‐thiadiazine 1,1‐dioxides 7, 8 using m‐chloroperoxybenzoic acid. Oxidation of 5, 6 with hydrogen peroxide furnished isothiazol‐3(2H)‐one 1,1‐dioxides 9, 10 as ring contraction products.
Synthesis of 1,4,5,6‐tetrahydropyrazolo[3,4‐d]pyrido[3,2‐b]azepine
Authors: Albright J. Donald , Du Xuemei
Published: May 2009

The synthesis of 7,8‐dihydro‐5(6H)‐quinolinone (3) from commercially available 3‐amino‐2‐cyclohexen‐1‐one (1) and 3‐(dimethylamino)acrolein (4) in 23% yield avoids the preparation of propynal (2). Conversion of 5‐(4‐methylphenylsulfonyl)‐6,7,8,9‐tetrahydro‐5H‐pyrido[3,2‐b]azepine (12) to 6‐(4‐methylphenylsulfonyl)‐1,4,5,6‐tetrahydropyrazolo[3,4‐d]pyrido[3,2‐b]azepine (24) is described. Removal of the N‐(4‐methylphenylsulfonyl) group with 40% sulfuric acid in acetic acid gave the tricyclic azepine 26. Application of a similar series of reactions to 5‐(4‐nitrobenzoyl)‐6,7,8,9‐tetrahydro‐5H‐pyrido[3,2‐b]‐azepine (13) afforded 6‐(4‐nitrobenzoyl)‐1,4,5,6‐tetrahydropyrazolo[3,4‐d]pyrido[3,2‐b]azepine (25).
Mechanism of the formation of 1,2,4‐thiadiazoles by condensation of aromatic thioamides and of N‐substituted thioureas
Authors: Forlani Luciano , Lugli Andrea , Boga Carta , Corradi Anna Bonamartini , Sgarabotto Paolo
Published: May 2009

The condensation reaction of thiobenzamide, (as well as thionicotinamide and isothionicotinamide) in the presence of dimethyl sulfoxide and of an acid, affords 3,5‐diphenyl‐1,2,4‐thiadiazole. Under the same experimental conditions, N‐substituted thioureas are also condensed to 1,2,4‐thiadiazole derivatives; their structure is ascertained by spectroscopic properties and by X‐ray diffraction. Some information on the mechanism of thiadiazoles formation from both starting classes of compounds, thiobenzamides and N‐substituted thiourea, is collected and discussed.
Carbene and radical pathways in pyrolysis of benzisoxazolones and benzotriazoles
Authors: Prager Rolf H. , Baradarani Mehdi M. , Khalafy Jabbar
Published: May 2009

A comparative study of the flash vacuum pyrolysis of a number of N‐alkyl and N‐acyl benzotriazoles and benzisoxazolones has confirmed that carbene derived pathways predominate at lower temperatures, and radical pathways at highter temperatures. Two new general unimolecular thermal reactions are also highlighted.
Preparation of 4‐substituted 3‐amino‐2‐chloropyridines, synthesis of a nevirapine analogue
Authors: Bakke J. M. , Riha J.
Published: May 2009

A new method for preparing 3‐amino‐2‐chloropyridines with a substituent (methyl, phenyl, carbox‐amide, methoxycarbonyl, acetyl, benzoyl and cyano) at the 4‐position has been developed. An isoquinoline analogue of the reverse transcriptase inhibitor Nevirapine has been synthesized from the 4‐amino‐3‐chloroisoquinoline.
Synthesis of heterocyclic nitrogen derivatives from aryl‐1,4‐benzoquinones
Authors: Hassan Mamdouh A. , Fandy Ragab F. , El‐Amine Tark M.
Published: May 2009

Treatment of 2‐aryl‐3,6‐bis(arylamino)‐1,4‐benzoquinones 2a‐h with different acid chlorides, namely acetyl, phenylacetyl and chloroacetyl chloride yields 3a,7a‐dihydropyrrolo[2,3‐f]indole‐2,6‐dione 3, 5‐(N‐phenylacetylarylamino)‐3‐phenylindole‐2,6‐dione 4 and 3‐chloro‐5‐(N‐chloroacetylarylamino)indole‐2,6‐dione 5 respectively. Stirring 2‐aryl‐1,4‐benzoquinones (1) with ethylenediamine and/or o‐phenyl‐enediamine in methylene chloride gives pyrazino[2,3‐g]quinoxalines derivative 6 and/or tetrapentacene derivative 7 respectively. The products 5‐aryl‐ and 6‐aryl‐1/H‐indazole‐4,7‐diones 8 and 9 were obtained in the 1,3‐dipolar cycloaddition of diazomethane to (1).
Synthesis of 11Z‐9‐demethyl‐9‐((3‐indolyl)methyl)retinal
Authors: Wada Akimori , Fujioka Naoko , Ito Masayoshi
Published: May 2009

A convenient synthesis of 11Z‐9‐demethyl‐9‐((3‐indolyl)methyl)retinal, which has an amino acid residue of tryptophan at the 9 position in retinal, is described using a tricarbonyliron complex.
Density functional theory calculations and vibrational spectra of 2‐bromo‐4‐chloro phenol and 2‐chloro‐4‐nitro phenol
Authors: Krishnakumar V. , Jayamani N. , Mathammal R. , Parasuraman K.
Published: May 2009

FTIR and FT Raman spectra of 2‐bromo‐4‐chloro phenol (BCP) and 2‐chloro‐4‐nitro phenol (CNP) were recorded in the region 4000–400 and 4000–50 cm−1, respectively. The molecular structure, geometry optimization, and vibrational wavenumbers were investigated. The spectra were interpreted with the aid of normal coordinate analysis based on density functional theory (DFT) using the standard B3LYP/6‐31G** method and basis set combination and was scaled using multiple scale factors, which yield good agreement between the observed and calculated wavenumbers. The results of the calculations are applied to simulate the infrared and Raman spectra of the title compounds, which showed excellent agreement with the observed spectra. Copyright © 2009 John Wiley & Sons, Ltd.
Fibrinogen Patterns and Activity on Substrates with Tailored Hydroxy Density
Authors: Rodríguez Hernández José Carlos , Rico Patricia , Moratal David , Monleón Pradas Manuel , Salmerón‐Sánchez Manuel
Published: May 2009

The influence of the surface fraction of OH groups on fibrinogen (FG) adsorption is investigated in copolymers of ethyl acrylate and hydroxy ethylacrylate. The amount of adsorbed FG, quantified by western‐blotting combined with image analysis of the corresponding bands, decreases as the hydrophilicity of the substrate increases. The influence of substrate wettability on FG conformation and distribution is observed by atomic force microscopy (AFM). The most hydrophobic substrate promotes FG fibrillogenesis, which leads to a fibrin‐like appearance in the absence of any thrombin. The degree of FG interconnection was quantified by calculating the fractal dimension of the adsorbed protein from image analysis of the AFM results. The biological activity of the adsorbed FG is correlated to cell adhesion on FG‐coated substrates.

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Preparation of Size Tunable Amphiphilic Poly(amino acid) Nanoparticles
Authors: Kim Hyungjin , Akagi Takami , Akashi Mitsuru
Published: May 2009

Size tunable amphiphilic NPs composed of poly(γ‐PGA) and hydrophobic amino acids, such as Phe or Trp, were prepared. To prepare these size‐regulated NPs, γ‐PGA‐g‐Phe or γ‐PGA‐g‐Trp dissolved in DMSO was added to various concentrations of NaCl solution. The γ‐PGA‐Phe and γ‐PGA‐Trp formed monodispersed NPs, and the size of NPs can be easily controlled by NaCl concentration. The different‐sized NPs showed the same structure. The encapsulation of protein into the different‐sized NPs was successfully achieved and the size of protein‐encapsulated γ‐PGA‐Phe NPs was increased when protein was encapsulated.

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Emerging Concepts in the Pathophysiology of Type 2 Diabetes Mellitus
Authors: Surampudi Prasanth N. , John‐Kalarickal Jennifer , Fonseca Vivian A.
Published: May 2009

Type 2 diabetes mellitus is a multifactorial metabolic disorder. It is characterized by chronic hyperglycemia, insulin resistance, and a relative insulin secretion defect. The prevalence of type 2 diabetes mellitus has risen worldwide in large part because of an increase in obesity and sedentary lifestyles. The underlying pathophysiology and complications of type 2 diabetes mellitus are still being elucidated. Recent advances in diabetes research have helped us to gain a better understanding about insulin resistance and insulin secretion defects. The evolving understanding about the influence of the incretin effect, insulin signal transduction, adipose tissue, intra–islet cell communication, and inflammation is changing the way in which we view type 2 diabetes mellitus. This new understanding will eventually provide us with new treatment approaches to help patients who have type 2 diabetes mellitus. This article gives a review of the current and emerging concepts of the pathophysiology of type 2 diabetes mellitus. Mt Sinai J Med 76: 216–226, 2009. © 2009 Mount Sinai School of Medicine
Glycemic Targets for Patients with Type 2 Diabetes Mellitus
Authors: Hamnvik Ole‐Petter R. , McMahon Graham T.
Published: May 2009

Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high‐risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all‐cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins. Mt Sinai J Med 76:227–233, 2009. © 2009 Mount Sinai School of Medicine
A fast parametric assignment algorithm with applications in max‐algebra
Authors: Gassner Elisabeth , Klinz Bettina
Published: May 2009

This article presents a fast algorithm for a class of parametric assignment problems. Moreover, it is shown how this algorithm can be applied to a problem arising in the so‐called max‐algebra which results as an analogue of classical linear algebra by replacing the classical addition and multiplication by a ⊕ b = max(a,b) and a ⊗ b = a + b, respectively. An instance of the linear parametric assignment problem is given by a bipartite graph G = (U,V,E) with 2n vertices, m edges and affine‐linear parametric edge weights cλ(i,j) = c(i,j) − b(i,j)λ for (i,j) ∈ E. The task is to find an assignment with minimum weight with respect to the parametric weights cλ for all values of λ. We develop an algorithm which solves the special case for which b(i,j) ∈ {0, 1} for all (i,j) ∈ E in 𝒪(mn+n2 log n) time. Our algorithm can be extended to solve the special parametric assignment problem which arises in connection with computing the essential terms of the so‐called characteristic max‐polynomial. The resulting algorithm runs in 𝒪(n3) time and thus improves upon the best‐known algorithm for computing the characteristic max‐polynomial due to Burkard and Butkovič (Appl Math 130 (2003), 367–380) by a factor of n. © 2009 Wiley Periodicals, Inc. NETWORKS, 2010