Coumarin, addition

Phytoalexins are low molecular weight compounds produced in plants as a defense mechanism against microorganisms. They do, however, exhibit toxicity to humans and other animals in addition to microbes (30). Coumarins, glycoalkaloids, isocoumarins, isoflavonoids, linear furanocoumarins, stilbenes, and terpenes aU. fall into the category of phytoalexins (31). Because phytoalexins are natural components of plants, and because their concentration may increase as a response to production and management stimuli, it is useful to recogni2e the possible effects of phytoalexins in the human diet. 

Fibrous stmctures represent a grain refinement of columnar stmcture. Stress-reHeving additives, eg, saccharin or coumarin, promote such refinement, as do high deposition rates. These may be considered intermediate in properties between columnar and fine-grained stmctures. 

The Perkin reaction is of importance for the iadustrial production of coumarin and a number of modifications have been studied to improve it, such as addition of a trace of iodine (46) addition of oxides or salts of metals such as iron, nickel, manganese, or cobalt (47) addition of catalytic amounts of pyridine (48) or piperidine (49) replacement of sodium acetate by potassium carbonate (50,51) or by cesium acetate (52) and use of alkaU metal biacetate... 

The couplings of vicinal protons in 1,2-disubstituted alkenes lie in the range 6-12 Hz for cis protons (dihedral angle 0°) and 12-17 Hz for trans protons (dihedral angle 180°), thus also following the Karplus-Conroy equation. Typical examples are the alkene proton AB systems of coumarin (16a, cis) and tra 5-cinnamic acid (16b), and of the cis-trans isomers 17a and b of ethyl isopente-nyl ether, in addition to those in problems 3, 4, 8, 11, 13 and 38. 

In addition to their work on naphthocoumarins, Sen and Kakaji showed that 4-t-butyl-2-hydroxyphenones 50 gave exclusively coumarins 51 when treated with various anhydrides in the presence of their corresponding sodium carboxylates. They saw similar results with 4-t-amyl-2-hydroxyphenones. 

The reaction of relatively simple starting materials, coumarin 40, piperidone 37 and ammonium acetate, leads in a single step to the complex bridged tetracyclic compound 44. The reaction can be rationalized by assuming formation of the iminc 38 from reaction of 37, with ammonia. Conjugate addition of the eneamine-like tautomer 39 to the excellent Michael acceptor 40 will... 

The 2D chromatograms reveal additional components of the natural mixtures. They also give a map of the essential oil, which is helpful in the identification of the components by the position and the characteristic colours of the derivatives on the plate. A further, considerable improvement in the separation performance can be obtained by using overpressured layer chromatography (OPLC). Harmala et al. (70) used 2D OPLC for the separation of coumarins from the genus Angelica. Figure 10.15 shows the one-dimensional (a) and two-dimensional (b) OPLC separations of 16 coumarins. 

In addition to effects on biochemical reactions, the inhibitors may influence the permeability of the various cellular membranes and through physical and chemical effects may alter the structure of other subcellular structures such as proteins, nucleic acid, and spindle fibers. Unfortunately, few definite examples can be listed. The action of colchicine and podophyllin in interfering with cell division is well known. The effect of various lactones (coumarin, parasorbic acid, and protoanemonin) on mitotic activity was discussed above. Disturbances to cytoplasmic and vacuolar structure, and the morphology of mitochondria imposed by protoanemonin, were also mentioned. Interference with protein configuration and loss of biological activity was attributed to incorporation of azetidine-2-carboxylic acid into mung bean protein in place of proline. 

These observations indicated that an intermolecular double condensation to give a bis N-(methylene-4-oxocoumarinyl)-l,4 aromatic diamine had occurred. Data from the elemental analysis indicated that the calculated and observed values were within the acceptable limits ( 0.4%) and in conformity with the assigned structure. In the addition of molar equivalents of 1,4-aromatic binucleophilic compounds to compound 72 we did not observe any heterocyclic compounds resulting from the further intermolecular nucleophilic attack on the single condensation product. Since the condensation of 3-(dimethylaminomethylene)-chromane-2,4-dione with aromatic binucleophilic compounds is the only route to the new coumarinic compounds, this represents a useful synthetic method. 

FIG. 4 Time-resolved fluorescence Stokes shift of coumarin 343 in Aerosol OT reverse micelles, (a) normalized time-correlation functions, C i) = v(t) — v(oo)/v(0) — v(oo), and (b) unnormalized time-correlation functions, S i) = v i) — v(oo), showing the magnitude of the overall Stokes shift in addition to the dynamic response, wq = 1.1 ( ), 5 ( ), 7.5 ( ), 15 ( ), and 40 (O) and for bulk aqueous Na solution (A)- Points are data and lines that are multiexponential fits to the data. (Reprinted from Ref 38 with permission from the American Chemical Society.)... 

In the emission spectra of coumarins 9a, 10a, 10c, and 9d in BSA/SDS mixture, the most pronounced bands revealed similar wavelengths to those in the presence of BSA. Observed Stokes shifts values for dyes 9a-d and lOa-d occurred between 8 and 102 nm. The fluorescence increase of the dye upon BSA/SDS addition varied from 2.5 times (9b) to 330 times (lOd), while the brightest complex resulted from dye 10a, its quantum yield being about 0.27. Despite the observed emission enhancement value, the fluorescence intensity of other coumarin dyes in the presence of BSA/SDS mixture was only low to moderate. 

B. Coumarilic acid. In a 5-1. three-necked flask fitted with a mechanical stirrer and reflux condenser, 450 g. (8 moles) of solid potassium hydroxide is dissolved in 700 ml. of absolute alcohol. The solution is cooled to 15° by immersing the flask in an ice bath, and 215 g. (0.7 mole) of finely divided coumarin dibromide is added in 10- to 15-g. portions to the well-stirred basic solution. The rate of addition is controlled so that the temperature never rises above 20° the addition requires about 30 minutes. After all the dibromide has been added, the reaction mixture is refluxed, with stirring, for 30 minutes (Note 7). One and a half liters of water is added, and the resulting solution is steam-distilled until 2.5 1. of distillate has been collected (Note 8). The residue is cooled to room temperature by the addition of 1 kg. of cracked ice (Note 9) and is then acidified by the addition of 1.2 1. of 6 N hydrochloric acid. The crude coumarilic acid is collected on a filter and stirred with 600 ml. of cold water. The acid is separated from the water by filtration, sucked as dry as possible on the filter, and then crystallized from a mixture of 250 ml. of alcohol and 250 ml. of water (Note 10). The recrystallized coumarilic acid is colorless, weighs 93-100 g. (82-88%) (Note 11), and melts at 190-193°. 

Coumarin dibromide has been prepared by the addition of bromine to coumarin in chloroform solution. 1-2... 

Besides their essential roles in nature, isoprenoids are of commercial importance in industry. Some isoprenoids have been used as flavors, fragrances, spices, and food additives, while many are used as pharmaceuticals to treat an array of human diseases, such as cancer (Taxol), malaria (artemisinin), and HIV (coumarins). In contrast to the huge market demand, isoprenoids are present only in low abundance in their host organisms. Thus, isolation of the required isoprenoids consumes a large quantity of natural resources. Furthermore, owing to their structural complexity, total chemical synthesis is often not commercially feasible. For these reasons, metabolic engineering may provide an alternative to produce these valuable isoprenoids [88,89]. 

Simple phenolic compounds include (1) the phenylpropanoids, trans-cinnamic acid, p-coumaric acid and their derivatives (2) the phenylpropanoid lactones called coumarins (Fig. 3.4) and (3) benzoic acid derivatives in which two carbons have been cleaved from the three carbon side chain (Fig. 3.2). More complex molecules are elaborated by additions to these basic carbon skeletons. For example, the addition of quinic acid to caffeic acid produces chlorogenic acid, which accumulates in cut lettuce and contributes to tissue browning (Fig. 3.5). 

Michael addition and intramolecular aldol condensation-elimination process to afford coumarin derivatives 523 and 524, respectively [236]. 

In an alternative strategy functionalized phenols, such as iodophenol, were involved in palladium-catalyzed carbonylation of alkynes or allenes, producing coumarin or chromone derivatives (Scheme 23) [130-133]. After oxidative addition of the iodoarene to the Pd(0) catalyst the order of insertion of either CO or the unsaturated substrate mainly depends on the nature of the substrate. In fact, Alper et al. reported that CO insertion occurs prior to allene insertion leading to methylene- or vinyl-benzopyranone derivatives [130]. On the contrary, insertion of alkynes precedes insertion of CO, affording couma-rine derivatives, as reported by Larock et al. According to the authors, this unusual selectivity can be explained by the inability of the acyl palladium species to further react with the alkyne, hence the decarbonylation step occurs preferentially [131-133]. 

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