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.     

Detection of 210 kDa receptor protein for a leaf-movement factor by using novel photoaffinity probes

Circadian rhythmic plant leaf-movement, called nyctinasty, is controlled by a time-course change in the internal concentration of the leaf-movement factor in the plant body. We revealed that specific binding proteins (210 and 180 kDa) for the leaf-movement factor, potassium lespedezate (1), are contained in the plasma membrane of the plant motor cell by using novel synthetic photoaffinity probes. These proteins are localized on the motor cell in the plant body, and would be potential receptors for the leaf-movement factor to control the leaf-movement. Our study is a rare successful result of the detection of membrane receptors by using a synthetic photoaffinity probe designed on a biologically active natural product. And these results also advance a guideline for probe design towards successful photoaffinity labeling.     

Iodine/Et3SiH: a novel reagent system for the synthesis of 3-aryl-1H-indenes from 1,3-diaryl propargyl alcohols

1,3-Diaryl propargyl alcohols undergo smooth intramolecular Friedel-Crafts cyclization with triethylsilane in the presence of 10 mol % iodine 3-aryl-1H-indene derivatives in good yields in short reaction times. This is the first example on the synthesis of substituted indenes from 1,3-diaryl propargyl alcohols. The use of inexpensive and readily available molecular iodine makes this method quite simple, more convenient, and practical.     

Iodine/MeOH: a novel and efficient reagent system for thiocyanation of aromatics and heteroaromatics

Indoles, pyrroles, oxindoles and aromatic amino compounds undergo smooth thiocyanation with ammonium thiocyanate in the presence of molecular iodine in methanol under mild conditions to afford the corresponding 3-indolyl, 2-pyrrolyl and 4-aryl thiocyanates, respectively, in excellent yields with high selectivity. The reactions proceed rapidly at room temperature without heating or the use of strong Lewis acids.     

Synthesis of ferrocenylcarbodiimide as a convenient electrochemically active labeling reagent for nucleic acids

Ferrocenylcarbodiimides carrying different redox potentials, 1 and 2, were designed and synthesized as convenient electrochemically active labeling reagents for nucleic acids, which may be used as dually labeling reagents of nucleic acids like Cy3 and Cy5 dyes. These reagents could react with the imino unit of thymine or guanine base on DNA or of uracil base on RNA under a basic buffer condition to yield a labeled product quantitatively in a short period of time. The current responses of the labeled DNAs in square wave voltammetric (SWV) measurement showed a good linear correlation with the amount of the hybridized ones. DNAs labeled with the two different reagents, 1 and 2, could be detected electrochemically at different potentials after hybridization with a DNA probe-immobilized gold electrode.     

1-Decanethiol, a new reagent for the odorless deprotection of aryl methyl ethers

1-Decanethiol has been found to be an excellent reagent for the deprotection of aryl methyl ethers. This newly developed protocol afforded the corresponding phenols in good to excellent yields. A clear advantage of 1-decanethiol over the more commonly used thiols is the easy extraction of both the deprotecting reagent and the reaction byproduct into the aqueous phase, which allows an essentially odorless work-up.     

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.     

FeCl3-NaI mediated reactions of aryl azides with 3,4-dihydro-2H-pyran: a convenient synthesis of pyranoquinolines

The tetrahydroquinoline moiety is an important structural component of a number of natural products. The reaction of aryl azides with 3,4-dihydro-2H-pyran in the presence of FeCl₃-NaI affords the corresponding tetrahydroquinoline derivatives in an efficient manner. Most of the cyclizations exhibited cis selectivity.     

Photodecarboxylative benzylations of phthalimide in pH 7 buffer: a simple access to 3-arylmethyleneisoindolin-1-ones

Photoadditions of phenylacetates to phthalimide in pH 7 buffer solution give the corresponding benzylated-hydroxyphthalimidines in moderate to high yields of up to 94%. In a micro-structured reactor, higher conversions and purities are achieved. With branched phenylacetates, photoaddition affords diastereoisomeric mixtures with low to moderate de values. Subsequent acid-catalyzed dehydration furnishes the corresponding 3-arylmethyleneisoindolin-1-ones in good to excellent yields and with high E-selectivities. Irradiation of the parent 3-phenylmethyleneisoindolin-1-one under oxidative conditions only leads to cis/trans-isomerization.     

Synthesis of a library of 2-aryl-2H-tetrazole-5-carboxamides for photoaffinity labeling of aminergic G-protein coupled receptors

A four-step approach to 2-aryl-2H-tetrazole-5-carboxamides bearing GPCR-focused N-substituted piperazine residues involves ‘SAFE’ diazotransfer onto 1-(piperazin-1-yl)butane-1,3-diones followed by [3+2] cycloaddition of arenediazonium cations at the intermediate ααα-diazo acetamides. The compounds prepared are intended for photoaffinity labeling of aminergic G-protein coupled receptors.     

Photolysis of 2-azidopyridines. the behavior of 1-(2-azido-6-chloropyrid-4-yl)-3-phenylurea,a photoaffinity labeling reagent for probing cytokinin-binding proteins

The photolysis of l-(2-azido-6-chloropyrid-4-yl)-3-phenylurea ( 1 ) was studied under various conditions. In alcohols or in hexane, complex mixtures of products were obtained. Methoxide anions or diethylamine gave rise in high yield to 1,3-diazepines resulting from ring enlargement of the intermediate nitrene with addition of one molecule of the nucleophile, and nucleophilic substitution of the chlorine atom. A similar reaction was observed in water, when Pyrex filtered light was used. However, with unfiltered light produced by a powerful lamp, the main reaction was photodechlorination. The reagent 1 is expected to bind covalently to cytokinin-binding proteins through different ways upon photolysis.     

Addition of aryl cuprates to azides: a novel approach for the synthesis of unsymmetrical diaryl amines

Aryl and benzyl azides react smoothly with aryl cuprates, generated in situ from aryl magnesium bromide and CuCN in THF to furnish a variety of unsymmetrical diaryl amines in good yields. This is the first report on the synthesis of diarylamines from aryl azides and aryl bromides via an organometallic approach.     

Synthesis and antitumor evaluation of C3/C3 fluoroquinolone dimers (I): Tethered with a fused heterocyclic s-triazolo[2, 1-b][1, 3, 4]thiadiazole

Five C3/C3 fluoroquinolone dimers tethered with a fused heterocyclic ring of s-triazolo[2,1-b][1,3,4]thiadiazole derived from antibacterial quinolones were synthesized and characterized, and their in vitro antitumor activity against L1210, CHO cell lines was evaluated via the respective IC50 values.     

Synthesis of functionalised cephalosporins : Diphenylmethyl(1S,6R,7S)-3-bromomethyl-7-formamido-7-methoxyceph-3-em-4-carboxylate-1-oxide: a useful intermediate in the preparation of 7α-methoxycephalosporins

The N-formamido cephalosporins 4a and4b undergo direct methoxylation at the Pα-position to give the 7α-methoxy derivatives 5a and 5b. These were converted to other 7β-acylamido compounds by the sequence : oxidation, deformylation, acylation and reduction. The 3-bromomethyl derivatives 2b,6b and 8b proved amenable to nucleophilic substitution with 5-mercapto-1-methyltetrazole.     

Development of a new protein labeling strategy, oxidation labeling. part 1: Preliminary evaluation and synthesis of tautomycin containing a metal coordinating unit

In the current work we present our preliminary evaluation of a new protein labeling strategy, namely oxidation labeling. We found that a bis(2-picolyl) amine analogue coordinating Cu⁺ was able to oxidize histidine to oxo-histedine in a small peptide by generating reactive oxygen species upon exposure to hydrogen peroxide. The bis(2-picolyl) amine unit was then incorporated into the natural product tautomycin via an oxime linker. The compound, which showed good activity toward protein phosphatase 1γ (PP1γ), will be used in oxidation labeling studies with PP1γ.     

exo-N-[2-(4-Azido-2,3,5,6-tetrafluorobenzamido)ethyl]-dC: a novel intermediate in the synthesis of dCTP derivatives for photoaffinity labelling

An alternative route for the synthesis of a photoaffinity labelling (PAL) dCTP derivative is reported. This method involves the intermediacy of exo-N-[2-(4-azido-2,3,5,6-tetrafluorobenzamido)ethyl]-dC. The latter is prepared from the coupling of known N-(2-aminoethyl)-4-azido-2,3,5,6-tetrafluorobenzamide, prepared in an improved three-step sequence, with an activated 4-triazolyl derivative of dU, followed by deprotection. ¹⁹F NMR spectroscopy proved extremely useful in following the synthetic transformations, and enabled control of any adventitious reduction of the azides.     

DMP （1,1,1-Triacetoxy- 1,1-dihydro- 1,2-benziodoxol-3（1H）-one）： A novel catalyst for synthesis of 2-substituted benzimidazoles derivatives

Various 2-arylbenzimidazoles were synthesized from o-phenylenediamine and aldehydes via one-step process using DMP (Dess-Martin-periodinane) reagent as an oxidant.The method was proved to be simple,convenient and the products were isolated with good yields(80-90%).     

1-bromo-1-lithioethene: a practical reagent for the efficient preparation of 2-bromo-1-alken-3-ols

A reliable preparative-scale synthesis of 1-bromo-1-lithioethene is reported. This reagent undergoes clean 1,2-addition with a range of aldehydes and ketones at -105 degrees C to afford the corresponding 2-bromo-1-alken-3-ols in moderate to excellent yield. Efficient diastereoselective addition to alpha-siloxy and alpha-methylcyclohexanones, as well as protected 3-keto furanose sugars, is achieved in the presence of 10 mol % CeBr(3). The resulting bromoallylic alcohol adducts have considerable potential as synthetic building blocks. [reaction: see text]     

1,3,5,7-Tetramethyl-8-aminozide-difluoroboradiaza-s-indacene as a new fluorescent labeling reagent for the determination of aliphatic aldehydes in serum with high performance liquid chromatography

A BODIPY-based fluorescent derivatization reagent with a hydrazine moiety, 1,3,5,7-tetramethyl-8-aminozide-difluoroboradiaza-s-indacene (BODIPY-aminozide), has been designed for aldehyde labeling. An increased fluorescence quantum yield was observed from 0.38 to 0.94 in acetonitrile when it reacted with aldehydes. Twelve aliphatic aldehydes from formaldehyde to lauraldehyde were used to evaluate the analytical potential of this reagent by high performance liquid chromatography (HPLC) on C₁₈ column with fluorescence detection. The derivatization reaction of BODIPY-aminozide with aldehydes proceeded at 60 °C for 30 min to form stable corresponding BODIPY hydrazone derivatives in the presence of phosphoric acid as a catalyst. The maximum excitation (495 nm) and emission (505 nm) wavelengths were almost the same for all the aldehyde derivatives. A baseline separation of all the 12 aliphatic aldehydes (except formaldehyde and acetaldehyde) is achieved in 20 min with acetonitrile–tetrahydrofuran (THF)–water as mobile phase. The detection limits were obtained in the range from 0.43 to 0.69 nM (signal-to-noise = 3), which are better than or comparable with those obtained by the existing methods based on aldehyde labeling. This reagent has been applied to the precolumn derivatization followed with HPLC determination of trace aliphatic aldehydes in human serum samples without complex pretreatment or enrichment method.