Thermochemical reaction of 7-azido-1-ethyl-6,8-difluoroquinolone-3-carboxylate with heterocyclic amines. An expeditious synthesis of novel fluoroquinolone derivatives

Novel 7-hydrazino-1-ethyl-6,8-difluoroquinolone-3-carboxylate derivatives are obtained by thermochemical reaction of 7-azido-1-ethyl-6,8-difluoroquinolone-3-carboxylate with heterocyclic amines. These new fluoroquinolone carboxylates could be used as precursors in the preparation of novel fluoroquinolone carboxylic acids. These latter compounds are known to have biological activity.     

Synthesis and In vitro biological activity of some 7-(5-aminomethyl-2-isoxazolidinyl)quinolone-3-carboxylic acids

The synthesis of the title compounds via nitrone cycloaddition is described. The in vitro antibacterial activity of these compounds is compared against 1-ethyl-6,8-difluoro-7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (CI-934).     

由2',4'-二氢-6'-甲氧基-3',5'-二甲基查耳酮合成新黄酮

在DMSO/ I2的氧化作用下,由2',4'-二氢-6'-甲氧基-3',5'-二甲基查耳酮可合成一种全新结构的黄酮:7-羟基-5-甲氧基-6,8-二甲基黄酮(产率91%),而在HCl/MeOH作用下则得到了两种黄烷酮:7-羟基-5-甲氧基-6,8-二甲基黄烷酮 (产率70%) 和 5,7-二羟基-6,8-二甲基黄烷酮 (产率20%).     

Synthesis of antimicrobial agents. II. Syntheses and antibacterial activities of optically active 7-(3-hydroxypyrrolidin-1-yl)quinolones

Two optically active isomers of 1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-hydroxypyrrolidin-1-yl)-4-oxoquinoline-3-carboxylic acid ( 10 ) were prepared. One of the isomer, 7-[(3S)-hydroxypyrrolidin-1-yl] derivative 8 , was about 4 times more potent in vitro than the other, 7-[(3R)-hydroxypyrrolidin-1-yl] derivative 4 , and approximately two times more active than the racemate, 7-[(3RS)-hydroxypyrrolidine-1-yl] derivative 10. Optical active 8 was the most active in in vivo, followed by 10 , and 4 was the least active compound. But, they were more potent than CI-934 12 and norfloxacin. From the results, (3S)-hydroxypyrrolidinyl group was found to be one of the beneficial group for PCA-anti-bacterial agent.     

具有绿色荧光发射效应的氟喹诺酮-铀(Ⅵ)配合物

A uranium(Ⅵ) complex [UO₂(1-ethyl-6,8-difluoro-7-(3-methyl-piperazinium-1-yl)-4-oxo-1,4-dihydro-quin-oline-3-carboxylate)(NO₃)₂] was obtained by the hydrothermal treatment of UO₂(NO₃)₂·6H₂O with lomefloxacin-HCl in water at 80 ℃ in Pyrex tube. The crystal belongs to monoclinic system, space group P2₁/c, with a=1.430(3) nm, b=1.032 1(18) nm, c=1.729(3) nm, β=106.67(3)°, V=2.458(6) nm³, Z=4. This complex is a good green fluorescent material in solid state at room temperature. CCDC: 660959.     

Synthesis of both the enantiomers of endo-brevicomin,the aggregation pheromone of Dryocoetes autographus

(1R,5S,7S)-(+)-endo-Brevicomin (7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane) and its (1S,5R),7(R)-(?)-isomer were synthesised employing the Sharpless asymmetric epoxidation as the key-step.     

Asymmetric Synthesis and DNA Intercalation of (-)-6-[[(Aminoalkyl)oxy]methyl]-4-demethoxy-6,7- dideoxydaunomycinones(1)(,)

The BF(3).Et(2)O-promoted Diels-Alder addition of 1-acetylvinyl RADO(Et)-ate (RADO(Et)-ate = 3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylate) to 1-(dimethoxymethyl)-2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane led to one major monoadduct that added to 1,2-didehydrobenzene and was converted into (-)-4-demethoxy-7-deoxydaunomycinone and (2R)-12-acetoxy-2-acetyl-5-(bromomethyl)-1,2,3,4-tetrahydronaphthacen-2-yl RADO(Et)-ate. The latter compound was used to construct (8R)-8-acetyl-6,8-dihydroxy-11-[[(3'-[(aminopropyl)oxy]-, -4'-[(aminobutyl)oxy], and -5'-[(aminopentyl)oxy]methyl]-7,8,9,10-tetrahydronaphthacene-5,12-dione hydrochloride (-)-8, (-)-9, (-)-10, respectively, as well as (8R)-8-acetyl-6,8-dihydroxy-11- [[[2'-[(3"-aminopropyl)amino]ethyl]oxy]- ((-)-11) and -[[3'-[(3"-aminopropyl)amino]propyl]oxy]methyl]-7,8,9, 10-tetrahydronaphthacene-5,12-dione hydrochloride ((-)-12). (8R)-8-Acetyl-6,8-dihydroxy-11-[[(alpha-L-daunosaminyl)oxy]methyl]-7,8,9,10-tetrahydronaphthacene-5,12-dione hydrochloride ((-)-13), a mimic of idarubicin, was also prepared. Absorbance and fluorescence titration experiments showed (-)-8, (-)-9, and (-)-10 to intercalate calf thymus DNA whereas (-)-11, (-)-12, and (-)-13 did not. The best intercalator was (-)-9 (K(b) = (1.1 +/- 0.1) x 10(5) M(-)(1)) with the [(4'-aminobutyl)oxy]methyl chain. Inhibition of topoisomerase II-induced DNA strand religation was observed for (-)-8 at a concentration of 50 &mgr;M.     

An efficient reduction of azide to amine: a new methodology to synthesize ethyl 7-amino-1-ethyl-6,8-difluoroquinolone-3-carboxylate and its spectroscopic characterization

Most of the quinolone antibacterial research has been focused on the functionality at C-7 position where the nature of substituents is responsible for antibacterial spectrum, potency, bioavailability, and side effects of the quinolones. Then, a 7-amino-fluoroquinolone could be the starting point of a wide variety of potentially useful compounds like tetracyclic and tricyclic quinolones or secondary amines with side chain derivatives. This attracted our attention to synthesize a 7-azide-fluoroquinolone, which could be converted to amine performing a photochemical reaction using CuI as catalyst. FT-IR and H¹ NMR spectra of the final product, ethyl 7-amino-1-ethyl-6,8-difluoroquinolone-3-carboxylate, suggests the formation of dimers, a feature already observed in norfloxacin.     

Behaviour of 2-subst1tuted 6,8-dibromo-3,1-benzoxazin-4-ones towards o-phenylenediamine and anthranilic acid ; a case of unusual cleavage of 6,8-d1bromo-2-methyl-3,1-benzoxazin-4-one

6,8-Dibromo-2-methyl-3,l-benzoxazin-4-one (1) reacts with o-phenylenediamine to give a mixture of 3,5-dibromoanthranilic acid (2), 2-methylbenzimidazole (3) and 3-(o-aminophenyl)-6,8-dibromo-2-methylquinazolin-4-one (4). However, when the reaction was conducted in ethanol or in the absence of solvent at elevated temperature, a mixture of (2) & (3) was obtained. A similar cleavage of (1) took place when it was allowed to react with anthranilic acid yielding a mixture of (2) and N-acetylanthranilic acid (6). The reaction of o-phenylenediamine with 6,8-dibromo-2-phenyl-3,1-benzoxazin-4-one (7) proceeded normally to give 3-(o-aminophenyl)6,8-dibromo-2-phenylquinazolin-4-one (8) or 2-benzoyl-amino-3, 5-dibromo-N-(o-aminophenyl)benzamide (9), depending upon the reaction conditions.     

Synthesis and Crystal Structure of 4-(2-Methylene-1-ethyl-3,3-dimethylindoline-2'-yl)-6,8-dibromo- 1'-ethyl-3',3'-dimethylspiro-[3,4-dihydro-2H-1-benzopyran-2,2'-indoline]

The title compound of 4-(2-methylene-1-ethyl-3,3-dimethylindoline-2'-yl)-6,8-dibro-mo-1'- ethyl-3',3'-dimethylspiro[3,4-dihydro-2H-1-benzopyran-2,2'-indoline],C33H36Br2N2O,as a dicondensed spiropyran (DC) has been synthesized by indoline in ethanol with 3,5-dibromo-salicyaldehyde.The compound was characterized by elemental analysis and IR spectra.Meanwhile,the crystal of the compound was obtained and determined by X-ray single-crystal diffraction.Crystal data: monoclinic system,space group P21/n,a=12.9699(15),b=12.5196(13),c=19.327(2) (A),β=106.493(3)°,Mr=636.46,V= 3009.1(6) (A)3,Z=4,F(000)=1304,Dc=1.405 g/cm3,μ=2.722 mm-1,R=0.0554 and wR=0.1176 for 6892 independent reflections (Rint=0.0354) and 5699 observed reflections (I>2σ(I)).     

Synthesis and Crystal Structure of 4-（2-Methylene-1-ethyl-3,3-dimethylindoline-2＇-yl）-6,8-dibromo-1＇-ethyl-3＇,3＇-dimethylspiro-[3,4-dihydro-2H-1-benzopyran-2,2＇-indoline]

The title compound of 4-(2-methylene-1-ethyl-3,3-dimethylindoline-2'-yl)-6,8-dibro-mo-1'-ethyl-3',3'-dimethylspiro[3,4-dihydro-2H-1-benzopyran-2,2'-indoline],C33H36Br2N2O,as a dicondensed spiropyran(DC) has been synthesized by indoline in ethanol with 3,5-dibromo-salicyaldehyde.The compound was characterized by elemental analysis and IR spectra.Meanwhile,the crystal of the compound was obtained and determined by X-ray single-crystal diffraction.Crystal data:monoclinic system,space group P21/n,a=12.9699(15),b=12.5196(13),c=19.327(2),β=106.493(3)°,Mr=636.46,V=3009.1(6) 3,Z=4,F(000)=1304,Dc=1.405 g/cm3,μ=2.722 mm-1,R=0.0554 and wR=0.1176 for 6892 independent reflections(Rint=0.0354) and 5699 observed reflections(Ⅰ 2σ(Ⅰ)).     

Synthesis of 7-benzoxazol-2-yl and 7-benzothiazol-2-yl-6-fluoroquinolones

The fluoroquinolones, 7-benzoxazol-2-yl-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 7-benzothiazol-2-yl-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, were synthesized. The compounds were obtained by use of the Gould-Jacobs route to the quinoline ring system. The required anilines, 3-benzoxazol-2-yl-4-fluorophenylamine and 3-benzothiazol-2-yl-4-fluorophenylamine were obtained by the cyclodehydration reaction of 5-amino-2-fluorobenzoic acid with 2-aminophenol or 2-aminothiophenol respectively using polyphosphoric acid.     

Reactivity of some 3-substituted-6,8-dimethylchromones toward some nucleophilic reagents

The reactivity of 3-substituted-6,8-dimethylchromone derivatives 1 - 5 was investigated toward selected nucleophilic reagents namely; 3-amino-1,2,4-triazole, 2-aminobenzimidazole, 7-chloro-4-hydrazinoquinoline, and 5,6-diphenyl-3-hydrazino-1,2,4-triazine. These nucleophiles were allowed to react with 6,8-dimethylchromone-3-carboxaldehyde ( 1 ) through condensation with the aldehyde group with opening of γ-pyrone ring giving compounds 6 , 7 , 10, and 11 . Reactions with 6,8-dimethylchromone-3-carbonitrile ( 2 ), and 6,8-dimethylchromone-3-carboxylic acid ( 3 ) occur via attack at position 2 in both compounds followed by cycloaddition onto the nitrile function (in case of carbonitrile 2 ) or decarboxylation and cyclocondensation with the carbonyl group (in case of carboxylic acid 3 ). The current nucleophilic reagents reacted with simple condensation products 4 and 5 , in boiling dioxane, through nucleophilic addition at the exocyclic vinyl bond followed by addition at the CN group giving 6,8-dimethylchromone linked various heterocyclic systems 20 - 27 .     

Synthetic antibacterials. VIII. 7-(1′-alkylhydrazino)-1,8-naphthyridines and related compounds

Synthesis and in vitro antibacterial activity of 7-(1′-alkylhydrazino)-1,8-naphthyridines related to nalidixic acid were investigated. Namely, treatment of 7-alkylamino-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids 1a-d with sodium nitrite in the presence of hydrochloric acid gave the 1-ethyl-1,4-dihydro-7-(N-nitrosoalkylamino)-4-oxo-1,8-naphthyridine-3-carboxylic acids 2a-d , which upon reacting with zinc dust in acetic acid gave the 7-(1′-alkylhydrazino)-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacids 3a-d. The compound 3a was alternately obtained by the reaction of 7-chloro-1-ethyl-1,4-dihydro-4-oxo-1,8-naphth-yridine-3-carboxylic acid ( 4 ) with methylhydrazine. The reaction of 7-chloro-4-hydroxy-1,8-naphthyridine-3-carboxylic acid ( 5 ) with methylhydrazine gave the 4-hydroxy-7-(1′-methylhydrazino)-4-oxo-1,8-naphthyridine-3-carboxylic acid ( 6 ), which upon treatment with alkyl halides afforded the 1-alkyl-1,4-dihydro-7-(1′-methyl-hydrazino)-4-oxo-1,8-naphthyridines 3a and 3e-g. The reaction of the appropriate 3 with ketones gave the corresponding 7-(1′-methylalkylidenehydrazino)-1,8-naphthyridines 7a-c and 8a-b. Among the compounds prepared, certain 3 and 7 exhibited good activity against Gram-negative bacteria.     

Bioactive isocoumarins from a terrestrial Streptomyces sp. ANK302

Four isocoumarins have been isolated from the terrestrial Streptomyces sp. ANK302, namely 6,8-dimethoxy-3-methylisocoumarin (1), 6,8-dihydroxy-3-methylisocoumarin (2), 6,8-dihydroxy-7-methoxy-3-methylisocoumarin (3), and 6,7,8-trimethoxy-3-methylisocoumarin (4). Compound 1 is a new naturally-occurring isocoumarin, and 2 was isolated as a new bacterial product. The structures 1-4 were deduced from high resolution mass, 1D and 2D NMR spectra and by comparison with related compounds from the literature. Compound 2 showed a strong zoosporicidal activity at a concentration of 5 microg/mL against a phytopathogenic oomycete, Plasmopara viticola, and 1 was active against     

Reactions of tetrafluoroethene oligomers. Part 4. Some reactions of the major hexamer oligomer with nucleophiles based on oxygen and sulphur

The major hexamer oligomer of tetrafluoroethene [perfluoro-2-(1-ethyl-1-methylpropyl)-3-methyl-pent-1-ene] (1) reacted with sodium hydroxide under vigorous conditions to afford perfluoro-[(1-ethyl-1-methylpropyl) (1-methylpropyl)]keten (3). Reaction of (1) with methoxide ion in methanol afforded 4-methoxycarbonyl-heneicosafluoro-3,5-dimethyl-5-ethyl-hept-3-ene (5) whereas reaction with methanol In the presence of triethylamine initially afforded (5), but on further reaction yielded (E, Z)-4H-heneicosafluoro-3,5-dimethyl-5-ethylhept-3-ene (4). Reaction of (1) with potassium-t-butoxide in t-butanol afforded (3) whilst with water/triethylamine (4) was obtained. With ethanethiol and sodium benzylthiolate, respectively, hexamer (1) gave ethyl and benzyl [tricosafluoro-3-ethyl-3-methyl-2-(1-methylpropyl)pent-1-enyl]sulphides (6) and (7). With aqueous potassium cyanide 1-cyanotricosafluoro-3-ethyl-3-methyl-2-(1-methylpropyl)pent-1-ene (8) was obtained.     

Synthesis and theoretical study of pyrrole formiate derivatives through ring contraction of 1,4-dihydropyridines

Pyrrole formiate derivatives were synthesized through ring contraction of corresponding 3-carboxylate-1,4-dihydropyridines (3-CDHPs) mediated by 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). 2-Carboxylate-3-aryl-1H-pyrroles (2) and 3-carboxylate-4-aryl-1H-pyrroles (3) were obtained under readily accessible reaction conditions. To gain deep insights into this transformation, DFT calculations were carried out to establish the plausible reaction mechanism. The result revealed that the processes, including release of hydrogen, coupling with TEMPO, ring-opening of DHP scaffold, cleavage of ON bond in TEMPO moiety, fabrication of pyrrole scaffold and dissociation of formyl were incorporated in the transformation, which was confirmed further by the characterization of a byproduct and the detection of key intermediates using the LC-MS method.     

Stereoselective synthesis from D-glucose of (−)-∂-multistriatin (component of the European elm bark beetle, Scolytus multistriatus, aggregation pheromone).

A six step stereoselective synthesis of (−)-∂-multistriatin [(1S,2S,4S,5R)-5-ethyl-2,4-dimethyl-6,8-dioxabicyclo[3.2.1]octane, 1] is presented, starting from 2,4-O-ethylidene-D-erythrose (2), which is readily available from D-glucose.     

Rearrangement of some chlorosubstituted 3-amino-3,4-dihydro-1-hydroxycarbostyrils in hydrogen halide acids

The general conditions and results of rearrangement studies of the 5-, 6-, 7-, and 8-chloro-substituted 3-amino-3,4-dihydro-1-hydroxycarbostyrils in concentrated hydrochloric and hydro-bromic acids to the corresponding dihalosubstituted 3-amino-3,4-dihydrocarbostyrils have been described. The 5-, 7- and 8-chlorocarbostyrilhydroxamic acids undergo nucleophilic displacement by either chloride or bromide ion preferentially at the 6-position to form the respective 5,6-, 6,7- and 6,8-dihalolactams. However, with the 3-amino-6-chloro-3,4-dihydro-1-hydroxycarbo-styril where the 6-position is blocked, nucleophilic displacement by halide ions occurs at the 8-position to afford the 6,8-dihalolactams. The 6,8-dichloro- and 6,8-dibromolactams were also prepared by alternative halogenation procedures for purposes of comparison with the rearrangement products.     

Studies on quinoline derivatives and related compounds. VI. A novel displacement reaction of 1-ethylquinolinium iodides with nucleophiles

The reaction of 4-amino- ( 3a ) and 4-anilino-3-carbethoxy-1-ethyl-6,7-methylenedioxy-quinolinium iodide ( 3b ) with nucleophilic reagents produced 7-substituted 4-amino-3-carboxy-1-ethyl-6-hydroxyquinolinium betaines ( 5b-d ) and 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-phenylimino-3-quinolinecarboxylic acid ( 6b-d ), respectively, which led to 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-oxo-3-quinolinecarboxylic acids ( 1b-d ) by alkaline hydrolysis. With a variety of 1-ethyl-1,4-dihydroquinoline carboxylates ( 16a-e ) these novel displacement reactions were attempted.