Methoxycoumarin

A different approach to design a self-calibrating dye was proposed [70], in which a viscosity-sensitive molecular rotor (2-cyano-3-(4-dimethylaminophenyl) prop-2-enoic acid) was covalently linked to a reference dye, 7-methoxycoumarin-3-carboxylic acid, which exhibited no viscosity sensitivity (40, Fig. 13). A ratiometric measurement, that is, rotor emission relative to reference emission, was shown to be widely independent of dye concentration [70]. However, the design of such a ratiometric dye poses some challenges because of resonance energy transfer from... 

Berthelot, T, Talbot, J. C, Lain, G, Deleris, G. and Latxague, L. (2005). Synthesis of N epsilon-(7-diethylaminocoumarin-3-carboxyl)-and N epsilon-(7-methoxycoumarin-3-carboxyl)-L-Fmoc lysine as tools for protease cleavage detection by fluorescence. J. Pept. Sci. 11,153-160. 

Ito, K., and Sawanobori, J. (1982) 4-Piazomethyl-7-methoxycoumarin as a new type of stable aryldia-zomethane reagent. Synth. Comm. 12, 665. 

Furanocoumarins from Ruta graveolens possess antifungal activity to several plant pathogenic fungi. 7-Hydroxycoumarin, 4-hydroxycoumarin, and 7-methoxycoumarin were active against Colletotrichum species that cause Anthracnose disease of strawberry. 

Carbonylazides can also be used for fluorescent labeling of both primary and secondary hydroxyl groups. Including in this class of reagents are 7-me-thoxycoumarin-3-carbonylazide and 7-methoxycoumarin-4-carbonylazide (181). 

Fluorometric detection has been mainly employed for the determination of aminopenicillins such as amoxicillin and ampicillin in edible animal products because it confers the advantages of selectivity and sensitivity. Fluorometric detection of penicillins, however, necessitates their precolumn derivatization to produce the corresponding fluorescent derivatives. The most commonly used derivatizing reagents are formaldehyde (100, 117, 118), salicylaldehyde (83), and mercury dichloride (91). 4-Bromomethyl-7-methoxycoumarin has also been employed as a fluorescence label for the selective and sensitive detection of seven penicillins in milk (96). 

A comparison of the photobehavior of two crystals, 7-methoxycoumarin (19) and methyl m-bromo-cinnamate (20), exemplifies the importance of the need for the existence of free volume close to the reaction site [133-135]. Neither of these molecules is topologically oriented for efficient reaction in the crystal, meaning that the reactive pairs need to undergo some inter-molecular realignment before they can dimerize. 

Figure 22. Packing arrangement of 7-methoxycoumarin in the crystals—a unit cell representation. Note the two reaction centers (darkened circles) are twisted with respect to each other.

The reaction of 2,2-dimethyl-4,6-dioxo-l,3-dioxane (Meldrum s acid 394) and its analogues with 3-dialkylaminophenols has been used to prepare some fluorescent 7-dialkylamino-4-hydroxycoumarins (Scheme 127) (77M499). The substituted malonic acid (395) or its dehydration product is a possible intermediate, since it is known that diaryl-malonic esters are accessible from phenols and the 1,3-dioxane. 3-Methoxyphenol yields the pyrano[3,2-c]benzopyran-2,5-dione (396) in this reaction, presumably by annelation of another ring on to initially formed 4-hydroxy-7-methoxycoumarin. 

Several approaches have been made to calculate 13C chemical shifts of coumarins by MO methods. Good correlations were found between the 13C chemical shift values of coumarin (also protonated) and the n charge densities calculated by the CNDO/2 method [962], and of coumarins with it charge densities calculated by the Hiickel MO method (which, however, fails for methoxylated coumarins) [965]. Chemical shifts of mono- and dimethoxycoumarins have been correlated with parameters determined by refined INDO MO calculations, in which n bond orders, atom-atom polarizabilities, excitation energies and electron-nucleus distances were taken into consideration [966], In 3-substituted 4-hydroxy and 4-hydroxy-7-methoxycoumarins chemical shifts were found to be related to Swain and Lupton s parameters iF and M [388], according to equation 5.4 (SE = Substitution Effect) ... 

Fig. 8 Serum PC molecular species distribution after 6 weeks of treatment for both the placebo control group (A) and the drug-treated group (B). The molecular species were derivatized with 7-methoxycoumarin-3-carbonyl azide prior to analysis and detected by fluorescence with excitation at 340 nm and emission at 370 nm. (Reprinted from Ref. 91 with the permission of the Journal of Lipid Research.)...

Figure 1. Disposition of the Reactive Double Bonds C(3)-C(4) and C(3 )-C(4 ) of 7-Methoxycoumarin in the Asymmetric Unit.

Figure 4 Duration of irradiation versus yield-irradiation time given in hours for 7-methoxycoumarin and 7-chlorocoumarin (topochemical reaction) irradiation in days for 4-methyl-6-chlorocoumarin (defect-initiated reaction)...

The case of 7-methoxycoumarin with no associated nonrigid groups was analyzed for librational motion about the molecular axes using the program THMB... 

Figure 9 Molecular packing of 7-methoxycoumarin in the unit cell (top) and relative orientation of the reacting parameters.

With the exception of 7-methoxycoumarin, the examples discussed are all with only one molecule in the asymmetric unit in the unit cell, and the reaction takes place between this molecule and the one obtained by a symmetry operation—either a center of inversion or translational symmetry. Table 9 records a few examples where the unit cell has two independent molecules (A and B) in the asymmetric unit. 

Lam, S. and Grushka, E., Labeling of fatty acids with 4-bromomethyl-7-methoxycoumarin via crown ether catalyst for fluorimetric detection in high-performance liquid chromatography, J. Chromatogr., 158, 207, 1978. 

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