bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron‐impact induced fragmentation of 2‐substituted pyridines and picolines
Authors: Keller G. H. , Bauer L. , Bell C. L.
Published: April 2009

The fragmentation patterns obtained upon electron impact on 2‐nitro‐, 2‐chloro, and 2‐aminopyridines, as well as those of the corresponding 3‐, 4‐, 5‐ and 6‐picolines were examined. There was considerable departure from those patterns reported for the corresponding benzenoid derivatives. Although the molecular ion from 2‐nitro‐3‐picoline did not show fragment ions attributable to an “ortho‐effect” (unlike o‐nitrotoluene), those from 2‐chloro‐ and 2‐amino‐3‐picolines did show a loss of HCl and NH3, respectively. Quite unexpectedly the ions from 2‐chloro‐ and 2‐amino‐6‐picolines also lost HCl and NH3. Such meta‐eliminations for the 2‐substituted‐6‐picolines are postulated to be preceeded by either hydrogen or methyl migration. The mass spectra of 2‐pyridone, 2‐pyridthione and their respective 3‐, 4‐, 5‐ and 6‐methyl analogs were also studied. The primary fragmentations of the 2‐pyridones were as expected from those reported in the literature. The ions from 3‐ and 6‐methyl‐2‐pyridones lost water also, the former being another example of an “ortho‐effect” observed in this series. Of the thiones, the fragmentations of 3‐methyl‐2‐pyridthione proved most unique since its molecular ion showed besides the loss of HS, the pronounced elimination of H2S, the latter presumably due to an “ortho‐effect.” Figures are presented to illustrate the patterns and metastable ions are indicated when found for the transitions discussed.
Solvent‐free fluorination of partially‐chlorinated heterocyclics: Synthesis of 2,6‐difluoropyridine from 2,6‐dichloropyridine
Authors: Boudakian Max M.
Published: April 2009

Previous studies on the solvent‐free fluorination of partially‐chlorinated heterocyclics such as 2‐chloropyridine, 2,3,4,6‐ and 2,3,5,6‐tetrachloropyridine, and 2,4,6‐trichloropyrimidine with alkali metal fluorides or hifluorides revealed an inconsistent product pattern: degradation, partial or complete halogen exchange could occur. The present study concerned application of the solvent‐free halogen exchange technique (potassium fluoride) to 2,6‐dichloropyridine (I). The latter, as well as its fluorination products, exhibited good stability at 400° to provide an 80% yield of 2,6‐difluoropyridine (III). Moderation of fluorination conditions also permitted isolation of the precursor, 2‐chloro‐6‐fluoropyridine (II), a new compound. The above solvent‐free process to III is superior to the previously‐reported halogen‐exchange route in dimethyl sulfone solvent on the basis of yield, reaction time and number of processing steps.
The synthesis of oxygen analogs of cepham. A new bicyclic system
Authors: Sheehan John C. , Dadiac Miroslav
Published: April 2009

The synthesis of a new bicyclic system has been reported. Three substituted 5,6‐dihydro‐1,3‐oxazines have been condensed to a fused β‐lactam ring system by use of phthaloylglycyl chloride. The resulting phthalimido compounds were dephthaloylated to the corresponding oxygen analogs of cepham (2).
A convenient synthesis of certain 1‐(β‐D‐ribofuranosyl)benzotriazoles
Authors: Revankar Ganapathi R. , Townsend Leroy B.
Published: April 2009

The synthesis of 5,6‐dichloro‐1‐(β‐D‐ribofuranosyl)benzotriazole (4a), 5,6‐dimethyl‐1‐(β‐D‐ribofuranosyl)benzotriazole (4b) and 1‐(β‐D‐ribofuranosyl)benzotriazole (4c) in good yield has been accomplished by the condensation of the appropriate 1‐trimethylsilylbenzotriazole (1a, 1b, and 1c) with 2,3,5‐tri‐O‐acetyl‐D‐ribofuranosyl bromide (2) followed by subsequent deacetylation of the reaction products. The assignment of anomeric configuration and site of glycosidation for all nucleosides reported is discussed.
The synthesis of polymethylquinolines and 1,10‐phenanthrolines
Authors: Case Francis H. , Wisneski Harris H.
Published: April 2009

Several polymethyl‐1,10‐phenanthrolines were synthesized by the use of 3‐methyl‐3‐penten‐2‐one in Skraup reactions. The behavior of this ketone as well as that of 4‐hydroxy‐2‐pentanone and 4‐hydroxy‐3‐methyl‐2‐bulanone with various substituted anilines was studied.
The conversion of azobenzenes to phenazines: A new molecular rearrangement
Authors: Abramovitch R. A. , Davis B. A.
Published: April 2009

When azobenzenes arc heated with ferrous oxalate or with a fused mixture of aluminum chloride and sodium chloride the corresponding phenazines are formed in low yield. Azobenzene itself is exceptional in giving benz[c]cinnoline with AlCl3‐NaCl. Azoxybenzenes and ferrous oxalate give azobenzenes and some phenazines, while azoxybenzene itself also gives 2‐hydroxyazobenzene via a Wallach‐type rearrangement. The rearrangements are thought to occur at the surfaces of the reagent. No rearrangement to the phenazines occurs in the absence of the reagent.
Studies on the syntheses of heterocyclic compounds. Part CCLXXIII. Synthesis of C‐nordihydrocorynantheol and its related compounds
Authors: Kametani T. , Ihara M. , Suzuki T. , Shima K.
Published: April 2009

Mannich reaction of tryptamine with 3,3,4‐triethoxycarbonylhexaldehyde (IV) gave the cyclized product (VIII), whose hydrolysis, followed by decarboxylation, afforded the acid (IX). After esterification of IX, reduction of ester (X) with lithium aluminum hydride gave the C‐nordihydrocorynantheol (II). The syntheses of IV and XV were also described. Furthermore, the Mannich reaction of L‐N‐benzyl‐1‐methyltryptophan methyl ester (XV) with IV was also examined. This reaction gave the ester (XVII), which was hydrolyzed and decarboxylated to give the acid (XVIII). Esterification of XVIII, followed by catalytic hydrogenation, gave the lactam (III).
An improved synthesis of various racemic polyphenolic tetrahydroisoquinoline alkaloids
Authors: Teitel S. , Brossi A.
Published: April 2009

An improved and straightforward synthesis of (±)‐coclaurine (Va), (±)‐isococlaurine (Vb), (±)‐reticuline (VIIIa) as well as an alternate route to an intermediate in the synthesis of (±)‐multifloramine, the (±)‐diphenol (VIIIb), is described.
Carbonyl and thiocarbonyl compounds. XI. Synthesis of halogenated benzodioxoles by the action of tetrahalo‐o‐benzoquinones on benzophenone hydrazones and their cleavage by nucleophilic reagents
Authors: Latif N. , Zeid I. , Haggag B.
Published: April 2009

p,p′‐Dichloro‐, p,p′‐dimethyl‐ and p,p′‐dimethoxybenzophenone hydrazones react with tetrachloro‐ and tetrabromo‐o‐benzoquinone to give directly the halogenated benzodioxoles (IIIa‐IIIf), respectively, together with the corresponding tetrahalocatechol. Cleavage of the dioxole ring by nucleophilic reagents depends markedly on the nature of the substituents. The dimethoxyderivatives (IIIc) and (IIIf) proved to be unusually reactive toward cleavage by dilute mineral acids, lithium aluminum hydride, hydrazines and malonitrile, whereas the dichloro analog behaves normally and is not cleaved under the same conditions.
A new synthesis of 4‐thiouracils
Authors: Lamon Robert W.
Published: April 2009

Ethoxycarbonyl isothiocyanate has been found to form adducts with enamines which, on treatment with primary amines or ammonia, undergo apparent “amine exchange” and cyclization to 4‐thiouracil derivatives. Evidence for the 4‐thiouracil structure includes both spectral data and chemical transformations.
The synthesis of pyrimido[4,5‐d] pyridazines
Authors: Kinoshita Toshio , Castle Raymond N.
Published: April 2009

The synthesis of pyrimido[4,5‐d]pyridazin‐2‐one‐4‐thione (II), pyrimido[4,5‐d]pyridazine‐2,4‐dithione (VI), 4‐aminopyrimido[4,5‐d]pyridazine‐2‐thione (III), 2‐aminopyrimido[4,5‐d]‐pyridazin‐4‐one (X), 2‐methylpyrimido[4,5‐d]pyridazin‐4‐one (XII), and pyrimido[4,5‐d]‐pyridazin‐4‐one (XIII) are reported together with several new pyridazine intermediates.
A facile synthesis of 5‐substituted 1‐methyluracils and cytosine
Authors: Sakai Ted. T. , Pogolotti Alfonso L. , Santi Daniel V.
Published: April 2009

A facile, general synthesis for a number of 5‐substituted‐1‐methyluracils and cytosine which is suitable for the preparation of micro‐quantities is reported. In contrast to other methods, the 5‐substituent plays no role in determining the position of alkylation. 1‐Methyl‐5‐hydroxymethyluracil and 1‐methyl‐5‐formyluracil have also been synthesized by an alternate route.
Synthesis of thia‐ellipticine, 5,11‐dimethylbenzothieno[2,3‐g]isoquinoline
Authors: Fujiwara Allan N. , Acton Edward M. , Goodman Leon
Published: April 2009

1,4‐Dimethyldibenzothiophene (VII) was synthesized and was converted with butyl dichloromethyl ether to the 2‐aldehyde (VIII). The structure was confirmed by an independent synthesis of the 2‐ester (XI) derived from it. The 2‐aldehyde (VIII) with aminoacetaldehyde diethylacetal formed the Schiff′s base (IX), and Pomeranz‐Fritsch cyclization with 105% superphosphoric acid then formed thia‐ellipticine (II), an isostere of the antitumor alkaloid, ellipticine.
1‐Methyl‐3‐phenyl‐3‐thiocyanato‐1H,3H‐quinoline‐2,4‐dione: A novel thiocyanating agent
Authors: Klásek Antonín , Mrkvička Vladimír
Published: April 2009

Under mild reaction conditions, the thiocyanato group is selectively transferred from 1‐methyl‐3‐phenyl‐3‐thiocyanato‐1H,3H‐quinoline‐2,4‐dione (3) to some nucleophiles. Aliphatic primary and secondary amines are converted to S‐cyanothiohydroxylamines, anilines afford p‐thiocyanatoanilines, Wittig reagent is thiocyanated in α‐position, and thiols are oxidized to disulfides.
Synthesis of 10‐Aryl‐10H‐naphtho[1,8a,8‐fg]indazol‐7‐ones
Authors: Stadlbauer Wolfgang , Hojas Gerhard
Published: April 2009

3‐Hydroxy‐2‐[1‐(arylhydrazono)ethyl]‐1H‐phenalen‐1‐ones 3, obtained from 2‐acetyl‐3‐hydroxy‐1H‐phenalen‐1‐one (1) and arylhydrazines 2, cyclize under acidic conditions to 8‐methyl‐10‐aryl‐10H‐naphtho‐[1,8a,8‐fg]indazol‐7‐ones 4. Indazoles 4 are also obtained from 2‐acetyl‐3‐hydroxy‐1H‐phenalen‐1‐one (1) and arylhydrazines 2 in a one‐pot reaction. 2‐Acetyl‐3‐azido‐1H‐phenalen‐1‐one (6) does not give 8‐methyl‐9‐arylamino‐9H‐naphtho[1,8a,8‐fg]indazol‐7‐ones via azide decomposition but gives again by nucleophilic replacement of the azide moiety in 6 the indazole 4.
The chemistry of 1,6‐dioxapyrenes part 3 : Scope and limitations of an acid catalyzed ring‐closing reaction
Authors: Christensen Jørn B. , Bechgaard Klaus
Published: April 2009

One of the few methods for synthesis of 1,6‐dioxapyrenes is the acid catalyzed cyclization of 2,6‐disubstituted 1,5‐bis(2‐oxoalkoxy)naphthalenes. The scope and limitations of this reaction has been investigated and 11 new 2,7‐disubstituted 1,6‐dioxapyrenes have been prepared and characterized. Most of the compounds undergo two reversible oxidations to give the corresponding radical as well as di‐ cations.
8‐Fluoro‐4‐hydroxy‐1H‐[1,2,4]triazino[4,5‐a]quinoline‐1,6(2H)‐dione: Synthesis and reactivity
Authors: Edmont Doloràs , Chenault Jacques
Published: April 2009

A simple and versatile methodology to synthesise 4‐hydroxy‐1H‐[1,2,4]triazino[4,5‐a]quinoline‐1,6(2H)‐dione from methyl 6‐fluoro‐4‐oxo‐1,4‐dihydro‐2‐quinolinecarboxylate has been developed. It involves car‐bohydrazide formation followed by a condensation with triphosgene to form the fused [1,2,4]triazino ring. In addition, the reactivity of the [1,2,4]triazino ring has been studied.
Utilization of cleavage of the [1]benzofuro[2,3‐e][1,2,4]triazine ring for the synthesis of oxygen, nitrogen and sulfur derivatives of [1,2,4]triazine
Authors: Stýskala Jakub , Slouka Jan , Wiedermannová Iveta , Bednář Petr
Published: April 2009

A series of 6‐azacytosines 4a‐4k and 5a‐5c were prepared by nucleophilic cleavage of furan ring of [1]benzofuro[2,3‐e][1,2,4]triazine derivative 1. Some of them were used for the preparation of derivatives of [1,2,4]triazolo[4,3‐d][1,2,4]triazine (6a‐6d) and tetrazolo[1,5‐d][1,2,4]triazine (7). The reaction of 1 with hydrogen sulfide afforded the corresponding 6‐(2‐hydroxyphenyl)‐2‐phenyl‐5‐thioxo‐4,5‐dihydro‐1,2,4‐tri‐azin‐3(2H)‐one (8), while with hydrogen selenide 6‐(2‐hydroxyphenyl)‐2‐phenyl‐4,5‐dihydro‐1,2,4‐triazin‐3(2H)‐one (9) was formed. The prepared compounds were tested for biological activity.
On triazoles XLVIII. Synthesis of isomeric amino‐thiazolo‐[1,2,4]triazole, amino‐[1,2,4]triazolo‐[1,3]thiazine and ‐[1,3]thiazepine derivatives
Authors: Prauda Ibolya , Reiter József
Published: April 2009

Isomeric type 1 and 2 amino‐1,2,4‐triazoles condensed with thiazole, thiazine and thiazepine rings were synthesised from 5‐amino‐2,3‐dihydro‐1H‐1,2,4‐triazol‐3‐thione and α,ω‐dihaloalkanes through the 5‐amino‐3‐(ω‐haloalkylthio)‐1H‐1,2,4‐triazole intermediates. The reaction conditions leading to derivatives 1 and 2, respectively, were determined. A general and safe method for the unambiguous differentiation between structures 1 and 2 was offered by their cmr spectra.
Synthesis, lipophilicity and structure of 2,5‐disubstituted 1, 3, 5‐dithiazine derivatives
Authors: Winfield Leyte , Zhang Chunming , Reid Christy A. , Stevens Edwin D. , Trudell Mark L. , Izenwasser Sari , Wade Dean
Published: April 2009

A series of 2,5‐disubstituted 1,3,5‐dithiazine derivatives were synthesized as potential analogues of the potent dopamine uptake inhibitor GBR 12909. The lipophilic character of the 1,3,5‐dithiazine derivatives were experimentally (log P) and computationally (clog P) determined. The in vitro binding affinities of the 2,5‐disubstituted 1,3,5‐dithiazine derivatives at the dopamine transporter were determined to be much less potent than the binding affinity of GBR 12909 due to steric and electronic effects inherent to the 1,3,5‐dithiazine ring system. The X‐ray crystal structure of 2‐(2‐[bis(4‐fluorophenyl)methoxy]ethyl)‐5‐(3‐phenylpropyl)‐1,3,5‐dithiazine (7) revealed that the 5‐(3‐phenylpropyl) group is in a pseudo‐axial orientation and syn to the 2‐ethoxybenzhydryl moiety.
Synthesis of N1‐substituted coumarino[4,3‐c] pyrazoles
Authors: Čačič Milan , Trkovnik Mladen , Has‐Schön Elizabeta
Published: April 2009

3‐Acyl‐4‐hydroxy‐2‐oxo‐2H‐chromen derivatives 1a‐d were condensed with (7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl)‐acetic acid hydrazide 2, (4‐methyl‐2‐oxo‐2H‐chromen‐7‐yloxy)‐acetic acid hydrazide 3, and (7‐hydrazinocarbonylmethoxy‐2‐oxo‐2H‐chromen‐4‐yl)‐acetic acid hydrazide 4, to give corresponding 3‐alkyl‐1‐[2‐(7‐hydroxy‐2‐oxo‐2H‐chromeno‐4‐yl)‐acetyl]‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 5a‐d, 3‐alkyl‐1‐[2‐(4‐methyl‐2‐oxo‐2H‐chromeno‐7‐yloxy)‐acetyl]‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 6a‐d, and 1‐{4‐[(3‐alkyl‐1H‐chromeno[4,3‐c]pyrazole‐4‐one‐1‐yl)‐carbonylmethyl]‐2‐oxo‐2H‐chromen‐7‐yloxy‐acetyl}‐3‐alkyl‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 7a‐d.
Synthesis of tricyclic pyrido[2,3‐b][1,4]‐thiazines via nucleophilic substitution of activated precursors
Authors: Weber Manuela , Jäger Walter , Erker Thomas
Published: April 2009

Pyrido‐anellated compounds analogous to tricyclic 1,4‐benzothiazine derivatives were synthesized. Thus, under mild reaction conditiones substitution of thiolactim 3 with different N‐nucleophiles yielded the precursors for compounds, which were cyclized in a further step to the corresponding tricyclic derivatives.
Direct synthesis of γ‐substituted phthalides via ortho‐aryl benzoic acid mediated benzyl radical cyclization
Authors: Mahmoodi N. O. , Salehpour M.
Published: April 2009

Direct synthesis of γ‐substituted phthalids from related ortho‐aryl benzoic acids with 48–85% yield are covered. The direct oxidation in the presence of peroxydisulphate‐copper (II) chloride in aqueous medium was applied. The reaction is highly regioselective and leads exclusively to γ‐butyrolactone, through very stable benzylic radical intermediate.
Reactions of isocyanates with methyl N‐(cyanothioformyl)anthranilate
Authors: Deck L. M. , Papadopoulos E. P. , Smith K. A.
Published: April 2009

The triethylamine‐catalyzed reactions of methyl N‐(cyanothioformyl)anthranilate (1) with isocyanates result in cyclization involving the cyano group to form methyl 2‐(4‐imino‐2‐oxo‐3‐substituted‐5‐thioxoimi‐dazolidin‐1‐yl)benzoates (4). Ring closure at the ester carbonyl to form 3‐aryl‐3,4‐dihydro‐4‐oxoquinazo‐line‐2‐carbonitriles (8) is observed when the S‐methyl derivative of 1 is allowed to react with aromatic amines.
A facile one‐pot synthesis of novel substituted 1,2,3,4‐tetrahydropyrimidines
Authors: Karim Enamul , Kishore Kaushal , Vishwakarma Jai N.
Published: April 2009

A facile one‐pot synthesis of 5‐benzoyl‐6‐methylthio‐1,2,3,4‐tetrahydropyrimidines in good yields is reported.
Synthesis of new 4,5,6,7‐tetrahydro‐3H‐imidazo[4,5‐c]pyridine derivatives
Authors: Braña Miguel F.
Published: April 2009

The synthesis of new ligands for the H3histamine receptor is described. These new compounds are spinacine derivatives obtained by alkylation or Michael reaction at C6 position.
Synthesis, X‐ray crystal structure and biological activities of α‐phenoxyl‐1,2,3‐thiadiazoleacetamide
Authors: Zhao Wei Guang , Li Zheng Ming , Yang Zhao
Published: April 2009

The annelation of 1,2,3‐thiadiazole rings was accomplished by the reaction of N‐acylhydrazone 2a bearing an adjacent α‐methyl with thionyl chloride to give α‐chloro‐N‐methyl‐1,2,3‐thiadiazole‐4‐acetamide 4 and was demonstrated by the X‐ray crystal structure of its derivative 5a. A novel series of α‐substituted phenoxy‐N‐methyl‐1,2,3‐thiadiazole‐4‐acetamide 5 were synthesized through the reaction of the compound 4 and phenols. The results of bioassays show that the title compounds exhibit good anti‐HBV activities. The crystal of compound 5a, N‐methyl‐α‐2‐bromophenyl‐1,2,3‐thiadiazole‐4‐acetamide, has been prepared and determined by X‐ray diffraction.
Application of baylis‐hillman methodology in a new synthesis of 3‐oxo‐2,3‐dihydro‐1H‐isoindoles
Authors: Song Young Seok , Lee Chang Hoon , Lee Kee‐Jung
Published: April 2009

The Baylis‐Hillman reaction of 2‐cyanobenzaldehyde with some activated alkenes leading to the formation of 3‐oxo‐2,3‐dihydro‐1H‐isoindoles has been described.
Synthesis of sydnonimine derivatives as potential trypanocidal agents
Authors: Soulère Laurent , Hoffmanna Pascal , Bringaud Frédéric
Published: April 2009

N‐(p‐Nitrophenoxy)carbonyl‐3‐morpholino‐sydnonimine (NCMS) has been prepared from 3‐morpholinosydnonimine hydrochloride. Using the Griess assay and the superoxide‐mediated reduction of ferricytochrome c, the nitric oxide (NO•) and superoxide anion (O2•‐) ‐ releasing properties in phosphate buffer pH 7.4 of this novel peroxynitrite donor was studied and compared with the known 3‐morpholino‐sydnonimine (SIN‐1). From compound NCMS, a series of N‐substituted sydnonimine derivatives were easily prepared that contain purine or melaminophenyl groups which specify a recognition by a trypanosomal purine transporter. The ability of these new sydnonimines to inhibit the uptake of [23H]adenosine on Trypanosoma equiperdum was studied.
Liquid‐phase synthesis of mixture‐based bicyclic β‐lactam libraries
Authors: Gedey Szilvia , Fülöp Ferenc , Vainiotalo Pirjo , De Witte Peter A. M. , Zupkó Istvían
Published: April 2009

Five sets of 27‐membered combinatorial libraries of alicyclic β‐lactams were prepared via liquid‐phase Ugi 4‐center 3‐component reactions (U‐4C‐3CR) utilizing 3 different cis β‐amino acids, 3 different isonitriles and 5×3 sets of aldehydes. Through combinations of the building blocks of one of these libraries, all of the possible sublibraries were also generated. A few azetidinone derivatives were synthesized individually by parallel synthesis.
Synthesis of 1,2,5,6‐/1,2,3,6‐tetrahydropyridinyl‐tetrahydro‐cyclopentaisoxazole derivatives
Authors: Ahn Mija , Park Jung Mee , Lee Ihl‐Young Choi , Jung Myung Hee
Published: April 2009

Fused tetrahydrocyclopenta‐isoxazoles were synthesized by 1,3‐dipolar cycloaddition reactions with pyridinealdoxime or tetrahydropyridinealdoxime and cycloalkenes.
Metallation reactions. XXXIV. Synthesis of 2‐(1‐hydroxy‐1‐arylethyl)‐1,3‐benzoxathiol‐3‐oxide derivatives
Authors: Cabiddu Salvatore , Cadoni Enzo , Melis Stefana , Ianni Alen , Bernard Angela M. , Cabiddu Maria G. , De Montis Stefania , Fattuoni Claudia , Ianelli Sandra
Published: April 2009

The reaction of benzoxathiole‐3‐oxide with lithiumdiisopropylamide in tetrahydrofuran gave an anion, which was reacted with various aryl‐methyl‐ketones to give 2‐(1‐hydroxy‐1‐arylethyl)‐1,3‐benzoxathiol‐3‐oxide derivatives. The reaction was carried out in different temperature conditions: at ‐88 °C the trans addition stereoisomers to the sulfoxide oxygen atom were the main products.
A novel synthetic approach for the synthesis of pyridocarbazole alkaloids
Authors: Ergün Yavuz , Okaya Gürol , Patir Süleyman
Published: April 2009

The synthesis of 11‐methyl‐6H‐pyrido[4,3‐b]carbazole‐1(2H)‐one (5), which can be important for the synthesis of other pyridocarbazole alkaloids and especially 1‐substituted ellipticines, is described. Construction of the tetracyclic structure was achieved by a new route and two important precursor compounds (4a and 4b) for the synthesis of pyridocarbazole alkaloids and also many new tetrahydrocar‐bazole derivatives (7, 8, 9, 10, 11, 12, 13) were synthesized.
On triazoles XLIX. Synthesis of 5,6‐dihydrothiazolo[3,2‐b]‐[1,2,4]triazol‐2‐yl‐, 6,7‐dihydro‐5H‐[1,2,4]triazolo[5,1‐b][1,3]thiazin‐2‐yl‐, and 5,6,7,8‐tetrahydro[1,2,4]triazolo[5,1‐b] [1,3]thiazepin‐2‐yl‐isoquinolinium salts
Authors: Prauda Ibolya , Reiter József
Published: April 2009

5′‐Mercapto‐1′H‐1,2,4‐triazol‐3′‐yl‐isoquinolinium salts (6) were synthesised by the reaction of ortho‐acyl phenylacetones (2) or the corresponding pyrylium salts (3) and 5‐amino‐2,3‐dihydro‐1H‐1,2,4‐triazole‐3‐thione (5). Treatment of thioles 6 withα,ω‐dibromoalkanes led to type 15, 16 and 17 isoquinolinium salts condensed with thiazole, thiazine and thiazepine rings. When 6 are reacted with dibromomethane (10) 11 type dimeric structures are obtained.
A new intramolecular recyclization in water‐base cleavage reaction of 2,2‐dialkyl‐4‐hydroxymethylbenz[f]iso indolinium bromides and chlorides
Authors: Chukhajian Emma O. , Gevorkyan Hasmik R. , Chukhajian Eliza O. , Shahkhatuni Knarik G. , Panosyan Henrik A. , Tamazyan Rafael A.
Published: April 2009

The water‐base cleavage reaction of 2,2‐dialkyl‐4‐hydroxymethylbenz[f]isoindolinium bromides and chlorides (2b‐g) and (4a‐g) was investigated. It was established that the above‐mentioned salts in water‐base cleavage reaction undergo intramolecular recyclization. As a result 1,3‐dihydro‐4‐dialkylaminomethyl‐naphto[1,2‐c]furans (5a‐g) are obtained in 62‐72% yields. The same products in 65‐70% yields may be obtained by step cyclization cleavage reaction of dialkyl‐4‐hydroxybutyn‐2‐yl‐(3‐phenylpropargyl) ammonium salts (1b‐g) and (3a‐g), as well. The structure of the resulting amines 5a‐g are determined and approved by X‐ray diffraction, nmr and ir spectroscopic methods.
Synthesis of pyridazine derivatives through the unexpected intermediate 5‐amino‐ 4‐cyano ‐2,3‐dihydro‐furan‐2,3‐disulfonic acid disodium salt
Authors: Cacciari Barbara , Spalluto Giampiero , Ferretti Valeria
Published: April 2009

An unexpected compound (5‐amino‐4‐cyano‐2,3‐dihydrofuran‐2,3‐disulfonic acid disodium salt, 4) was isolated from the reaction of glyoxale bis hydrogen sulfite disodium salt with malononitrile. Its structure was undoubtly identified through crystal structure analysis. Compound 4 was highly stable and it was isolated easily and in a very high yield. Its reactivity was studied in the reactions with some hydrazine derivatives in order to obtain different pyridazine analogs.
1,3‐dipolar cycloaddition reactions of nitrile oxides to prop‐1‐ene‐1,3‐sultone
Authors: Tian Li , Xu Guo‐Yan , Ye Yong , Liu Lun‐Zu
Published: April 2009

The reaction of prop‐1‐ene‐1,3‐sultone 1 with a variety of nitrile oxides 3 afforded novel [3+2] cycloaddition products 4 in good yield. The cycloaddition reaction achieved excellent regioselectivity.
Synthesis of heterocycle‐substituted pyropheophorbide derivatives
Authors: Wang Jin‐Jun , Shim Young Key , Jiang Gui‐Ji , Imafuku Kimiaki
Published: April 2009

Methyl pyropheophorbide‐a (MPPa) (1) was converted to two aldehydes, methyl 2‐formylmethyl‐2‐devinylpyropheophorbide‐a (2) and methyl 2‐formyl‐2‐devinylpyropheophorbide‐a (3). The former 2 reacted with active methylene compounds having a cyano function in the presence of sulfur to afford thiophene‐substituted chlorins 5a‐c and reacted with arylhydrazines to yield indole‐substituted chlorins 6a‐d. From the latter 3, a α‐diketo chlorin 7 was obtained via Wittig reaction and oxidation. Compound 7 reacted with o‐phenylenediamine to afford 2‐quinoxalyl‐substituted pyropheophorbide‐a 8. The reaction of MPPa (1) with anthranilamide to give a spiro‐substituted compound 9.
Synthesis of some trifluoromethyl substituted 1‐methylpyrazoles
Authors: Pavlik James W. , Ayudhya Theppawut Israsena Na , Tantayanon Supawan
Published: April 2009

The major products from the reaction of β‐alkoxyvinyl trifluoromethyl ketones 1a‐c with methylhydrazine (2) in absolute ethanol are the 3‐(trifluoromethyl)‐substituted‐1‐methylpyrazoles 3a‐3c with lesser amounts of the 5‐(trifluoromethyl)‐substituted products 4a‐4c and 5a‐5c. Carrying out the reaction in non‐polar, aprotic solvents can further enhance the regioselectivity favoring the 3‐ (trifluoromethyl) ‐substituted isomers.
10‐Thia‐mesobilirubin‐xiiiα
Authors: Ghosh Brahmananda , Lightner David A.
Published: April 2009

The 10‐thia analog of mesobilirubin‐XIIIα, with the central C(10) CH2group replaced by sulfur (1a) was synthesized by condensation of neoxanthobilirubic acid (3) with sulfur dichloride. Thia‐rubin1ais a brilliant yellow solid, forming bright yellow solutions with uv‐visible absorption maximum from 425–440 nm.
Relationship between kernel size and shape and lipase activity of naked oat before and after pearling treatment
Authors: Hu XinZhong , Wei Yimin , Ren Changzhong , Zhao Jing
Published: April 2009

BACKGROUND: In China, some oat‐processing companies use pearling treatment to remove part of kernel lipase activity before further deactivation such as infrared roasting. Kernel size and shape are important physical properties of oat kernels. However, there are no reports concerning the change of oat kernel size and shape and lipase activity during pearling treatment.

RESULTS: In this research, we tested lipase activity in the kernels of four different oat varieties and we studied the relationship between kernel size and shape and lipase activity. The effect of pearling treatment on oat lipase activity was also examined. A TM‐05C Satake mill was employed to pearl oat samples, with different pearling times ranging from 0 to 45 s at 5 s intervals. The oat lipase activity, lipid content and kernel shape and size after the pearling treatment were tested. Results showed that not only oat variety but also kernel size and shape had marked effects on lipase activity. Pearling treatment could significantly reduce lipase activity. During pearling treatment, small changes in kernel size and shape could cause a dramatic decline in lipase activity.

CONCLUSIONS: Pearling treatment could be an effective pretreatment for further deactivation treatment of oats. Copyright © 2009 Society of Chemical Industry
Directed self‐assembly of single quantum dots for telecommunication wavelength optical devices
Authors: Dalacu D. , Reimer M.E. , Fréderick S. , Kim D. , Lapointe J. , Poole P.J. , Aers G.C. , Williams R.L. , Ross McKinnon W. , Korkusinski M. , Hawrylak P.
Published: April 2009

The ability to control the nucleation site of a single quantum dot will have a profound effect on the development of quantum dot‐based photonic devices. The deterministic approach will provide a truly scalable technology that can take full advantage of conventional semiconductor processing for device fabrication. In this review, we discuss the progress towards the integration of deterministically nucleated single quantum dots with top‐down quantum optical devices targeting telecommunication wavelengths. Advances in site‐controlled quantum dot nucleation using selective‐area epitaxy now makes it possible to position quantum dots at predetermined positions on a substrate in registry with alignment markers. This, in turn, has allowed for devices fabricated in subsequent processing steps to be aligned to individual quantum dots. The specific devices being targeted are gated‐single dots and coupled dot‐cavity systems which are key components of efficient sources of single photons and entangled photon pairs.
Radical cations of amino acids and peptides: Structures and stabilities
Authors: Hopkinson A.C.
Published: April 2009

Amino acid and peptide radical cations, M.+, are formed by oxidative dissociations of [Cu(auxiliary ligand)(M)].2+ and [MetalIII(salen)(M)]+ complexes. The most easily formed radicals contain either an aromatic or basic amino acid residue. Aromatic amino acids have low ionization energies, are easily oxidized and delocalize the charge and spin over the ring systems; basic amino acids facilitate formation of α‐radicals that have captodative structures in which the charge and spin are formally separated, although feeding back some of the charge onto the amide or carboxyl group adjacent to the radical center through hydrogen bonding enriches the electron‐withdrawing properties and is highly stabilizing. DFT calculations located five isomers of His.+ with an α‐radical with a captodative structure at the global minimum in a deep potential well. An IRMPD spectrum confirmed that this isomer is the experimentally observed “long‐lived” isomer. When both charge and spin are on the peptide backbone, as in [GGG].+, captodative structures have the lowest energies; the barriers to interconversion between the three isomeric α‐radicals of [GGG].+ are high as the charge impedes migration of a hydrogen atom. Dissociation of [GGG].+ is charge‐driven. In peptide radical cations containing a basic amino acid residue the charge is sequestered on the side chain and the radical center, either on the backbone or on another side chain, initiates the fragmentation. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:655–671, 2009
Comparison of vibrocompaction methods by numerical simulations
Authors: Arnold M. , Herle I.
Published: April 2009

Soils can be best compacted by repeated shearing. The strain amplitude plays an important role for the maximum compaction that can be reached. Experimental evidence emphasizes a vital impact of simultaneous multidirectional shear loading on the rate and magnitude of soil compaction. Two different vibrocompaction methods were analysed by the numerical simulations in the light of these findings. In an elastic finite element (FE) analysis, strain paths were determined. A strain amplitude‐dependent stiffness at small strains was introduced by multiple runs of the FE calculation to reach an appropriate stiffness for particular distances from the vibrator. Subsequently, the obtained strain paths were used to control single element simulations using hypoplasticity with intergranular strains. The calculated compaction profiles show three zones known from practical evidence: a limited compaction close to the vibrator, a zone of maximum compaction and a non‐densified zone remote from the vibrator. The deep vibrator produces a faster compaction than the top vibrator, especially in the more distant zone. The more efficient work of the deep vibrator can be attributed to a more general multidirectional shearing. Copyright © 2009 John Wiley & Sons, Ltd.
Study on the pharmacokinetics drug–drug interaction potential ofglycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats
Authors: Tang Jingcheng , Song Xiaohong , Zhu Min , Zhang Jinnan
Published: April 2009

Drug–drug interaction potentials of an herbal medicine namedGlycyrrhiza uralensiswas investigated in rats viain vitroandin vivopharmacokinetic studies. P450levels and the metabolic rate of lidocaine in the liver microsomes prepared from different treatment groups were measured. In a separatein vivopharmacokinetic study, the pharmacokinetic parameters of lidocaine in plasma and urine were estimated. P450levels in the rats pretreated byGlycyrrhiza uralensiswere significant higher than that in the non‐treatment control. The increase in P450levels was dose‐dependent.Glycyrrhiza uralensis(1 and 3 g/kg) increased P450levels by 62% and 91%, respectively, compared with the non‐treatment control (0.695 nmol/mg protein). The metabolic rate of lidocaine in the liver microsomes was significantly higher in the herb pretreated rats. The pharmacokinetic profile of lidocaine was significantly modified in the rats with the herbal pretreatment. Elimination half‐lives were shortened by 39%, and total clearances were increased by 59% with the pretreatment ofGlycyrrhiza uralensis. In conclusion,Glycyrrhiza uralensisshowed induction effect on P450isozymes. Efficacy and safety profiles of a drug may be affected when the herbal products or herbal prescriptions containing the plant medicine were concomitantly used. Copyright © 2009 John Wiley & Sons, Ltd.
Modelling the effects of thermal stratification on the oxygen budget of an impounded river
Authors: Becker Annette , Kirchesch Volker , Baumert Helmut Z. , Fischer Helmut , Schöl Andreas
Published: April 2009

The River Saar is a heavily impounded river with an average discharge of 80 m3 s−1. The German reach of the River Saar, i.e. the lower 90km, was gradually impounded from 1977–2000, resulting in a doubled average water depth (today 4.2m). In parallel to river development, water pollution was decreased strongly, relieving the critical oxygen budget in the river. Nowadays, oxygen concentrations may still fall below 4 mg O2 l−1 during low‐flow periods in summer, when thermal stratification and depth gradients of oxygen occur. In August 2005, high‐resolution measurements of temperature, conductivity, turbulence, as well as oxygen‐levels were carried out over 48 hours. These data were used to develop and validate a ‘quasi‐two‐dimensional’, depth‐resolving modelling approach with the deterministic water quality model QSim. This model includes the mathematical description of the influence of flow velocity and solar radiation on thermal stratification, on which the exchange between water layers depends. Three data sets of continuous measurements were compared with the model outputs. Thermal stratification shows diurnal rhythms and longitudinal variability depending on solar radiation, water depth, and flow velocity. In the course of the day, measurements and model outputs showed best agreement during the strongest stratification in the evening. The modelled effects of thermal stratification on oxygen‐budget rates were quantified and showed that the reduction of atmospheric re‐aeration is partly compensated by an increase in algal oxygen production. For the River Saar, the high temporal and spatial variability of oxygen concentrations documented here is of major ecological significance. Copyright © 2009 John Wiley & Sons, Ltd.
Catalytic isoforms Tpk1 and Tpk2 of Candida albicans PKA have non‐redundant roles in stress response and glycogen storage
Authors: Giacometti Romina , Kronberg Florencia , Biondi Ricardo M. , Passeron Susana
Published: April 2009

Candida albicans cAMP‐dependent protein kinase (PKA) is coded by two catalytic subunits (TPK1 and TPK2) and one regulatory subunit (BCY1). In this organism the cAMP/PKA signalling pathway mediates basic cellular processes, such as the yeast‐to‐hyphae transition and cell cycle regulation. In the present study, we investigated the role of C. albicans PKA in response to saline, heat and oxidative stresses as well as in glycogen storage. To fine‐tune the analysis, we performed the studies on several C. albicans PKA mutants having heterozygous or homozygous deletions of TPK1 and/or TPK2 in a different BCY1 genetic background. We observed that tpk1Δ/tpk1Δ strains developed a lower tolerance to saline exposure, heat shock and oxidative stress, while wild‐type and tpk2Δ/tpk2Δ mutants were resistant to these stresses, indicating that both isoforms play different roles in the stress response pathway. We also found that regardless of the TPK background, heterozygous and homozygous BCY1 mutants were highly sensitive to heat treatment. Surprisingly, we observed that those strains devoid of one or both TPK1 alleles were defective in glycogen storage, while strains lacking Tpk2 accumulated higher levels of the polysaccharide, indicating that Tpk1 and Tpk2 have opposite roles in carbohydrate metabolism. Copyright © 2009 John Wiley & Sons, Ltd.
Sacral Nerve Terminal Motor Latency in Patients With or Without Soiling More Than 2 Years After Low Anterior Resection for Low Rectal Cancer
Authors: Tomita Ryouichi
Published: April 2009

Background

To clarify the neurologic function with respect to puborectalis muscle (PM) in patients after low anterior resection (LAR) for low rectal cancer, author examined the sacral nerve terminal motor latency (SNTML) of the PM.

Methods

The latency of the response in the PM following transcutaneous magnetic stimulation of the cauda equina at the levels from S3 to S4 by SNTML was measured in 33 patients after LAR. They were divided into groups. Group A, which experienced soiling, comprised 15 patients (11 men, 4 women) aged 58 to 77 years (mean 63.5 years). Group A was further divided into patients having soiling with mucous secretions and feces on underwear on awaking everyday (group A1, 9 cases) and those with soiling during the daytime only when diarrhea occurred (group A2, 6 cases). Group B, which did not experience soiling comprised 18 patients (12 men, 6 women), aged 47 to 76 years (mean 62.2 years). The results from the groups were compared with data obtained from 33 control subjects (group C), who comprised 23 men and 10 women, aged 47 to 74 years (mean 62.4 years).

Results

The distance of the anastomosis from the dentate line (DL) in group A1 was significant shorter than in groups A2 and B (p = 0.0071, p < 0.0001, respectively). Patients in group A displayed significant prolongation of the SNTML values compared with patients in groups B and C at the right, left, and posterior sites (all p < 0.0001). Moreover, patients in group B showed more extended SNTML than those in group C at all sites. Patients in group A1 exhibited significant prolongation of the SNTML compared with patients in groups A2 and B at all sites (all p < 0.0001). Moreover, patients in group A2 showed more prolonged SNTML than those in group B at all sites. A significant correlation was found between the distance of the anastomosis from the DL and the SNTML values at all sites of the PM (right side: r = 0.786, p < 0.0001; left side: r = 0.739, p < 0.0001; posterior: r = 0.773, p < 0.0001).

Conclusions

Soiling after LAR may be caused by damage to the bilateral sacral motor nerves.
Alveolar echinococcosis of the liver in children
Authors: Yoshida Tadashi , Kamiyama Toshiya , Okada Tadao , Nakanishi Kazuaki , Yokoo Hideki , Kamachi Hirofumi , Matsushita Michiaki , Sato Naoki , Sasaki Fumiaki , Todo Satoru
Published: April 2009

Background/purpose

Alveolar echinococcosis of the liver (AEL) is a zoonosis that is distributed in cold regions of the northern hemisphere. The disease is mostly found in adults and rarely in pediatric patients because it tends to be slow growing.

Patients and methods

Ten Japanese pediatric patients (under 15 years old) with AEL have been operated on in Hokkaido University Hospital from January 1936 to June 2008. We examined these children and revealed the characteristics of AEL.

Results

The patients included three males and seven females whose mean age was 10.9 years old, ranging from 7 to 15. The length of follow‐up was from 3 months to 33 years (median 19 years). Six cases were picked up by mass screening; nine cases who underwent hepatectomy are still alive and one case whose tumors were unresectable died of liver failure.

Conclusion

Our cases indicate that some AEL pediatric patients advanced rapidly, so early detection is imperative. Thus, screening examinations are essential for children in contaminated areas and, if a liver tumor is found on a screening examination and diagnosed as AEL, complete radical resection should be performed.
French wasps in the New World: experimental biological control introductions reveal a demographic Allee effect
Authors: Fauvergue Xavier , Hopper Keith Roderick
Published: April 2009

Many populations introduced into a novel environment fail to establish. One underlying process is the Allee effect, i.e., the difficulty of individuals to survive and reproduce when rare, and the consequently low or negative population growth. Although observations showing a positive relation between initial population size and establishment probability suggest that the Allee effect could be widespread in biological invasions, experimental tests are scarce. Here, we used a biological control program against Diuraphis noxia (Mordvilko) (Hemiptera: Aphididae) in the United States to manipulate initial population size of the introduced parasitoid Aphelinus asychis Walker (Hymenoptera: Aphelinidae) originating from France. For eight populations and three generations after introduction, we studied spatial distribution and spread, density, mate‐finding, and population growth. Dispersal was lower in small populations during the first generation. Smaller initial population size nonetheless resulted in lower density during the three generations studied. The proportion of mated females and the population sex ratio were not affected by initial population size or population density. Net reproductive rate decreased with density within each generation, suggesting negative density‐dependence. But for a given density, net reproductive rate was smaller in populations initiated with few individuals than in populations initiated with many individuals. Hence, our results demonstrate a demographic Allee effect. Mate‐finding is excluded as an underlying mechanism, and other component Allee effects may have been overwhelmed by negative density‐dependence in reproduction. Impact of generalist predators could provide one potential explanation for the relationship between initial population size and net reproductive rate. However, the continuing effect of initial population size on population growth suggests genetic processes may have been involved in the observed demographic Allee effect.
Mixed Micellization and Interfacial Properties of Polyoxyethylene Sorbitan Esters with Cetylpyridinium Chloride: A Tensiometric Study
Authors: Rehman Nuzhat , Mir Mohammad Amin , Jan Musarat , Amin Adil , Dar Aijaz Ahmad , Rather Ghulam Mohammad
Published: April 2009

In this work a surface tensiometric method was used to study the effect of the chain length of non‐ionic surfactants, viz. ethoxylated sorbitan esters, on micellar composition, critical micellar concentration, mutual interaction parameter (β12), and activity coefficients of the mixed micelles formed with the cationic surfactant cetylpyridinium chloride at 25 °C. The micellar characteristics evaluated using the Clint, Rubingh, and Blankschtein models deviated significantly from ideality, and were used to ascertain the validity of these theories. Thermodynamic stability in terms of Maeda's approach and interfacial properties is also discussed.
Labyrinthitis ossificans: How accurate is MRI in predicting cochlear obstruction?
Authors: Isaacson Brandon , Booth Timothy , Kutz Joe W. , Lee Kenneth H. , Roland Peter S.
Published: April 2009

Objective

To determine the accuracy of preoperative MRI in predicting cochlear obstruction in pediatric patients with a history of bacterial meningitis.

Methods

A case series with chart review was performed at a tertiary care multidisciplinary cochlear implant program. Forty‐five children with hearing loss that resulted from bacterial meningitis were implanted from 1991 to 2006. Twenty‐five children had preoperative MRI with high‐resolution axial T2‐weighted images to assess for cochlear patency.

Results

Seventeen of 25 patients (68%) had surgical evidence of cochlear obstruction. Six patients (37.5%) required circummodiolar drill‐outs, and one patient (6.25%) underwent placement of a double array cochlear implant. The nine remaining patients (56%) with cochlear obstruction required removal of fibrous tissue or drilling of the inferior basal turn, but did not require manipulation of the ascending basal turn to achieve full electrode insertion. The sensitivity, specificity, and positive and negative predictive value of MRI predicting intraoperative cochlear obstruction with 95 percent confidence intervals was 94.1 percent (71–99), 87.5 percent (47–99), 94.1 percent (71–99) and 87.5 percent (47–99), respectively.

Conclusion

Preoperative high‐resolution T2 MRI may be useful in predicting cochlear obstruction in patients with a prior history of bacterial meningitis.
Undertreatment of allergy: Exploring the utility of sublingual immunotherapy
Authors: Emanuel Ivor A. , Parker Michael J. , Traub Oren
Published: April 2009

Allergic syndromes are highly prevalent and are comprised of a wide variety of clinical problems, including rhinitis, conjunctivitis, atopic dermatitis and urticaria, asthma, and food allergies. Numerous studies have shown that allergic syndromes are both underdiagnosed and undertreated. This is related to many factors, including trivialization of allergic conditions by physicians and patients, failure to adhere to diagnostic and treatment guidelines, and dissatisfaction with conventional pharmacologic treatments. Immunotherapy involves the administration of allergen extracts in an attempt to induce immunologic tolerance and has been used for the treatment of allergic syndromes and the prevention of long‐term complications. Conventional subcutaneous immunotherapy is effective but is also associated with a risk of serious adverse events, requires administration by a trained health care professional, and is contraindicated in certain populations. By contrast, sublingual immunotherapy has been used extensively in Europe and possesses most of the benefits of subcutaneous immunotherapy along with increased safety, tolerability, and convenience. This narrative review explores data from selected clinical studies and concludes that sublingual immunotherapy may be well suited to fill the gap posed by the undertreatment of allergic syndromes in the United States.
Article Commentary: Sublingual immunotherapy for inhalant allergy: Cautious optimism
Authors: Krouse John H.
Published: April 2009

Sublingual immunotherapy (SLIT) is being utilized with increasing frequency in both Europe and the United States. While the data with commercially‐prepared single‐antigen SLIT appear promising, there has been an extrapolation of these data beyond the scope of the well‐controlled clinical trials that have been published in the literature. In this environment of enthusiasm, it is prudent to examine variables that are relevant in evaluating how SLIT can be incorporated into American allergy practice on a broader scale. This commentary will discuss five areas of potential concern in moving toward wider implementation of SLIT: (1) patient selection for treatment; (2) pattern of sensitization; (3) dosing, preparation, and delivery; (4) safety concerns; and (5) cost of therapy. Additional research is necessary to adequately address these important issues to ensure that SLIT will offer a safe, well‐tolerated, and effective treatment for Americans with inhalant allergy.
The Precarious Life and Slow Death of the Mixed Courts of Egypt
Authors: Brown Nathan J.
Published: April 2009

Over the past century, most states of the Middle East have attempted to strengthen and centralize their legal systems, often following European models. Egypt undertook one of the first steps in that direction with its mixed-court system. These courts, which had jurisdiction in civil and commercial cases that involved a foreigner, however remotely, operated from 1876 until 1949. That this system could survive the political turmoil of those years, far outliving the circumstances which brought it into being, is remarkable.
From Prophetic Actions to Constitutional Theory: A Novel Chapter in Medieval Muslim Jurisprudence
Authors: Jackson Sherman A.
Published: April 2009

In his seminal and pioneering work, al-Risāla, al-Shafiʿi, the founder of juridical uṣul al-fiqh, laid down the following maxim:

God has obliged us to follow everything the Prophet instituted (sanna). And He has rendered adherence to this obedience to Him and turning away from it disobedience [to Him] for which He excuses no one.