Kinetics study of the photocleavage of (coumarin-4-yl)methyl esters

Photolabile coumarinylmethyl esters of biomolecules (caged compounds) are new tools for studying spatial and time-dependent aspects of signal transduction in living cells. Herein we describe a fluoresence spectroscopic method for the determination of the rate constants of the photolysis steps of such caged compounds using (6.7-dimethoxycoumarin-4-yl)methyl diethyl phosphate (DMCM-DEP) and sodium (6,7-dimethoxycoumarin-4-yl)methyl sulfate (DMCM-S). DMCM-DEP and DMCM-S are caged compounds which photorelease a proton, the corresponding acid anion, and the strongly fluorescent alcohol DMCM-OH upon excitation. The results of stationary and time-resolved measurements of the photochemistry and the luminescence of both caged compounds indicate that DMCM-OH is produced already during the excitation pulse. The quantitative analysis of the data demonstrates that the first step of the reaction--heterolytic bond cleavage of the coumarinylmethyl ester leading to the ion pair of a DMCM cation and an acid anion--is very fast with a rate constant of k1 approximately 2 x 10(10) s(-1). Recombination of the ion pair occurs with a rate constant of k(rec) approximately 2.3 x 10(9) s(-1) and is about 10 times faster than the competing hydrolysis reaction of the DMCM cation yielding DMCM-OH and a proton. Thus, both caged compounds belong to the fastest phototriggers known.     

Deactivation behavior and excited-state properties of (coumarin-4-yl)methyl derivatives. 2. Photocleavage of selected (coumarin-4-yl)methyl-caged adenosine cyclic 3',5'-monophosphates with fluorescence enhancement

A series of axial and equatorial diastereomers of (coumarin-4-yl)methyl-caged adenosine cyclic 3',5'-monophosphates (cAMPs), 1-6, having methoxy, dialkylamino, or no substituent in the 6- and/or 7-positions, and their corresponding 4-(hydroxymethyl)coumarin photoproducts 7-12 have been synthesized. The photochemical and UV/vis spectroscopical properties (absorption and fluorescence) of 1-6 and 7-12 have been examined in methanol/aqueous HEPES buffer solution. Donor substitution in the 6-position causes a strong bathochromic shift of the long-wavelength absorption band, whereas substitution in the 7-position leads only to a weak red shift. The photochemical cleavage of the caged cAMPs was investigated, and the photoproducts were analyzed. Photochemical quantum yields, fluorescence quantum yields, and lifetimes of the excited singlet states were determined. The highest values of photochemical quantum yields (photo-S(N)1 mechanism) were obtained with caged cAMPs having a donor substituent in the 7-position of the coumarin moiety, caused by electronic stabilization of the intermediately formed coumarinylmethyl cation. With donor substitution in the 6-position, the resulting moderate electronic stabilization of the coumarinylmethyl cation is overcompensated by the strong bathochromic shift, reducing the energy gap between the excited-state S(1) and the corresponding coumarinylmethyl cation. The rate constant for the ester cleavage and liberation of cAMP is about 10(9) s(-1), estimated for the axial isomer of 6 by analysis of the fluorescence increase of the alcohol 12 formed upon laser pulse photolysis.     

Mass spectrometry of N-(Pyrimidin-2-yl)amino acids and their methyl esters

N(Pyrimidin-2-yl)-glycine, -alanine and -phenylalanine (1-3) and their methyl esters (4-6) were investigated using electron impact (EI) mass Spectrometry. The results showed that EI-induced decomposition occurs on the carboxylic group or involves the loss of R₂OH. In contrast to earlier investigations on N-(pyrimidin-4-yl)amino acids, elimination of water (in 1-3) or methanol (in 4-6) was found to be of EI-induced nature. The loss of 'COOH from M⁺ of ester 4 suggests the occurrence of a skeletal rearrangement leading to the isomeric N-methylamino acid.     

Ortho effect in the mass spectrometric behaviour of N(pyrimidin-4-yl)aminobenzoic acids and their methyl esters

Ortho-. meta- and para-isomers of N-(pyrimidin-4-yl)aminobenzoic acid and their methyl esters were investigated by electron impact mass Spectrometry. Their fragmentation was found to be strongly dependent on the position of the substituent in the aminobenzoic moiety. Two different kinds of ortho effect were studied and confirmed with the aid of deuterium-labelled derivatives.     

Reactivity of methyl (3,6-dichloropyridazin-4-yl)acetate towards nucleophiles

Methyl (3,6-dichloropyridazin-4-yl)acetate (II), prepared from methyl (3,6-dihydroxypyrid-azin-4-yl)aeetate (1) by chlurination with phosphorus oxychloride, was used for studies of nucleo-philic displacement reactions and it has been found that only the chlorine atom at position 6 was displaced with hydrazine. With diluted hydrochloric acid both chlorine atoms were displaced with the 6-oxo isomer predominating. By turning the aromatic ring of pyridazine into an o-quinoid system, the chlorine atom at position 3 became mobile. Cyelization of (6-hydrazino-s-triazolo-[4,3-b ]pyridazin-7-yl)acetic acid hydrazide (XIX) gave 6-aminopyrrolo[3,2-e ]s-triazlo[ 4,3-b ]-pyridazm-7(8H)one (XXI).     

4-(3-Dialkylamino-2,5-dioxopyrrolidin-1-yl)benzoic acid esters

Reactions of alkyl 4-aminobenzoates with maleic anhydride give the corresponding alkyl 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoates, and the latter are converted into 4-(3-dialkylamino-2,5-dioxo-2,3,4,5-tetrahydro-1H-pyrrol-1-yl)benzoates by treatment with secondary amines.     

Synthesis of Some 2-(3-Alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles as Novel Antibacterial Agents

Abstract

Herein, we describe a one-pot synthesis of some novel 2-(3-alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) involving the reaction of 3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazole-1-thiocarboxamides (3) with 3-bromoacetylcoumarins (5) in the presence of sodium carbonate in ethanol. Reaction of 3 with 5 in the absence of sodium carbonate, however, resulted in the formation of 2-(3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles, which were subsequently dehydrated to 6 by refluxing in ethanol in the presence of sodium carbonate. The structure of the synthesized compounds (6) was confirmed by infrared (IR), mass, ¹H NMR, and ¹³C NMR spectra and elemental analysis data. Newly synthesized compounds (6) showed moderate to good activity against Gram-positive bacteria.     

The uses of 3-α-bromoacetylcoumarin in a novel syntheses of 3-(coumarin-3-yl) pyridazine and 3-(coumarin-3-yl) ketoximothiophene derivatives

Novel syntheses of bromohydrazones and ketoximes could be realized by reactions of 3-α-bromoacetylcoumarin with a variety of reagents. Such compounds reacted readily with nucleophiles to give unique heterocyclic systems. © 1996 John Wiley & Sons, Inc.     

Synthesis and Crystal Structure of N-methyl-N-((2-(p-tolyl)quinolin-4-yl)methyl)aniline

Compound 1, N-methyl-N-((2-(p-tolyl)quinolin-4-yl)methyl)aniline (C24H22N2), as a potential drug for the treatment of acid-related diseases has been synthesized via palladium-catalyzed intramolecular hydroarylation. The compound was characterized by MS and NMR spectra. Meanwhile, the crystal of 1 was obtained and determined by X-ray single-crystal diffraction. Crystal data: triclinic system, space group Pī, a = 5.548(5), b = 11.545(10), c = 14.546(12), α = 90.427(15), β = 90.727(14), γ = 101.099(16)°, V = 914.1(13)3, Z = 2, F(000) = 360, Dc = 1.230 g/cm3, μ = 0.072 mm-1, R = 0.0564 and wR = 0.1616 for 9768 independent reflections (Rint = 0.0447) and 3003 observed ones (I > 2σ(I)).     

Synthesis of methyl esters of 6-dialkylamino-2-(carbethoxy)-methylthiopyrimidine-4-carboxylic acids

A preparative method is proposed for the synthesis of methylesters of 6-dialkylamino-2-(carbethoxy)methylthiopyrimidine-4-carboxylic acids form the butyl ester of orotic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 818–821, June, 1986.     

Selective N-methylation of ethyl esters of 3-(1H-imidazol-4-yl)-2-propenoic acid

Methods of selective methylation of the nitrogen atoms of the ethyl ester of 3-(1H-imidazol-4-yl)-2-propenoic acid are reported. The nitrogen atom α to the ethylenic chain was methylated after protection of the β nitrogen with a phenacyl group.     

Synthesis and properties of bis(heteroazulen-3-yl)methyl cations and bis(heteroazulen-3-yl)ketones

The synthesis and properties of a novel type of bis(heteroazulen-3-yl)methyl cations, bis(2-oxo-2H-cyclohepta[b]furan-3-yl)methyl cation salt and nitrogen analogues, (9a-c·PF₆⁻) and (9a-c·BF₄⁻), as well as bis(heteroazulen-3-yl)ketones (12a-d) are studied. The synthetic method was based on a TFA-catalyzed electrophilic aromatic substitution on the heteroazulenes (6a-d) with paraformaldehyde to afford the corresponding disubstituted methane derivatives 7a-d, followed by oxidative hydrogen abstraction with DDQ, and subsequent exchange of the counter-anion by using aq. HPF₆ or aq. HBF₄. In addition, the reaction of 7a-d with 2.2 equiv. amounts of DDQ afforded carbonyl compounds 12a-d. The delocalization of the positive charge of 9a-c was evaluated by the ¹H and ¹³C NMR spectral data. The thermodynamic stability of cations 9a-c was evaluated to be in the order 9a<9b<9c on the basis of their reduction potentials measured by cyclic voltammetry (CV) and pK_R+ values (2.6-10.3) obtained spectrophotometrically. The reduction waves of cations 9a-c were irreversible, suggesting the dimerization of the radical species generated by one-electron reduction. This was demonstrated by the reduction of 9a·BF₄⁻ with Zn powder to give dimerized product 14a. In addition, the quenching of 9a·BF₄⁻ with MeOH/NaHCO₃ gives ether derivative 15a, which is proposed for the precursor for synthesizing tris(heteroazulene)-substituted methyl cations bearing two different heteroazulene-units.     

4-Hydroxy-2-quinolones. 35. Synthesis and study of antithyroid properties of 1H-2-oxo-3-(coumarin-3-yl)-4-hydroxyquinolines

The methyl ester of 1H-2-oxo-4-hydroxyquinoline-3-acetic acid is condensed in pyridine with salicylaldehydes to 1H-2-oxo-3-(coumarin-3-yl)-4-hydroxyquinolines. We present the results of a study of the effect of the synthesized compounds on thyroid function.Ukrainian Pharmaceutical Academy, Kharkhov 310002. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1100–1104, August, 1997.