Coumarins structure determination

Coumarins are pharmacologically active and have been used in the treatment of a diverse range of diseases. The great diversity of coumarin structures and their wide range of polarities present special problems for their simultaneous analysis. The separation of seven closely related coumarins by CZE was studied. Optimized conditions tallied with a 200 mM boric acid—50 mM tetraborate buffer pH 8.5 and were applied to the determination of coumarins in extracts from roots and aerial parts from the plant Chrysanthemum segetum. Baseline separation of six coumarins was achieved in 10 min. 

This limitation is well Illustrated by the failure of those methods to uncover the presence of another important group, the flavanoid, coumarin and cinnamic acid phenols (85 - 117). On the other hand, some 32 of these compounds were identified when isolation procedures specific for these types of compounds were employed. Using isolation and identification techniques which are particularly useful for alkaloids, it would be possible to determine whether any representatives of this class are present and, if so, to conduct subsequent studies for structure determination. 

Non-phenolic coumarins are relatively stable to oxidative conditions. Various oxidative methods were used extensively in structure determinations of natural flavones. 

The Laboratory of Lactones, Coumarins, and Terpenoids (headed by Prof. G.P Sidyakin) studied various plants for lactone content, particularly for the lactones leucomisine and austricine, which were isolated from Artemisia leucodes. Both lactones possess pronounced anti-inflammatory action. As a compound possessing pronounced angio-protective, hypolipidemic, hypo-cholesterolemic, and anti-inflammatory actions, leucomisine has passed medical tests and has been introduced into medical practice under the preparation name Oligvon. Since 1970, systematic studies of chemical compounds found in various species of the genus Ferula, which grows in the territory of Uzbekistan and adjacent republics, have been conducted. As a result, more than 50 species of Ferula have been investigated, from which more than 250 new terpenoids, coumarins, and esters have been isolated and their chemical structures determined. Natural esters of mono- and sesquiterpene alcohols with aromatic acids were discovered for the first time in this lab (Kurmukov and Akhmedkhodzhaeva 1994). 

Although predictions on the course of chemical progress can be widely off the mark, the main outlines of coumarin chemistry seem to be broadly established if one takes as a criterion, the new coumarin structures reported in the past decade. With the exception of a series of 3-substituted 4-hydroxy-5-methylcoumarins, probably biosynthesized from acetate and largely confined to the tribe Vernonieae (Compositae), most of the structures of new coumarins reported in this period are predictable variants of established structural patterns. Methods of coumarin isolation and structure determination are straightforward by modern standards. The literature contains a sizable data base of spectroscopic parameters making structure determination a fairly routine procedure. 

Lo, L. Liao, Y Kuo, C. Chen, C. A novel coumarin-type derivatizing reagent of alcohols Application in the CD exciton chirality method for microscale structural determination. Org. Lett. 2000, 2,683-685. 

In the early 1970 s potent acaricidal activity in 3-aryl-4-hy-droxy-coumarins. III, and 2-aryl-l,3-indanediones, IV, and their enol esters was discovered at Union Carbide (1,2). Extensive synthesis and screening of analogs in the dione and enol ester series led to the field test candidates Va and Vb, active against both motile forms (mite) and eggs. Va and Vb embodied certain structural and physicochemical features shown by published QSAR studies (2,3) to be important in determining the level of activity in the 1,3-indanedione series (1) the dimension D2 across the aryl ring must be near 7A and symmetry is preferred (2) the... 

Both direct and heavy-atom methods have been used to determine structures of substituted coumarins. Examples include 4-hydroxycoumarin and its 3-bromo derivative (65AX927, 66AX646) and the 7,8- and 6,7-dihydroxycoumarins, daphnetin and esculetin, respectively <76AX(B)946, 77AX(B)283). In the last compounds, hydrogen bonds link the molecules in the crystal. The stacking distances are comparable to those for other substituted coumarins <75AX(B)1287). A study of the structure of 7-hydroxy-4-methylcoumarin contains... 

Similarly, a substituted coumarin is converted into a benzofuran-2-carboxylic acid (291), a reaction which is useful in the determination of structure (73JCS(Pl)278l). 

An intriguing problem in the structure elaboration of coumarinolignans is the determination of the exact mode of linkage of the phenylpropanoid unit to the coumarin nucleus or, in other words, to decide which of two possible regioisomers the compound in question may be. This difficulty arises because no significant differences in conventional H- and NMR spectroscopic data are expected between two isomers under consideration and hydrogenolysis of the benzyl ether linkage has so far been unsuccessful. One of the earliest NMR methods used to... 

In the case of 7-diethylamino-4-(trifluoromethyl)coumarin ( coumarin-35 ), which has an amino group that is free to rotate, another competitive solvent-dependent decay path has been proposed rotation of the amino group of the planar ICT excited-state molecule can lead to a twisted intramolecular charge-iransfer (TICT) excited-state molecule, from which a radiationless decay to the ground-state molecule occurs [341], Solvent-dependent rate constants for both the radiative and nonradiative decay of excited-state coumarin dyes have been determined [341]. For critical discussions concerning the electronic structure of the excited states of 7-(dialkylamino)coumarins and 7-aminocoumarin ( coumarin-151 ), see references [341d, 341e]. 

Simultaneously, the advanced technology of mass screening was applied to an extensive chemical database [70], This process resulted in numerous hits including the coumarin and pyrone, 29 and 30, shown in Table 6. Both inhibitors exhibited micromolar potency. Because of their small size, achiral nature and their inhibitory activity, they became the prototypes for biological and chemical studies as well as for X-ray determination. The mass screening approach was also applied elsewhere and resulted in a very similar warfarin hit [71]. In both cases, the initial micromolar leads were elaborated to potent inhibitors through structure-... 

An X-ray cocrystal structure of racemic 44b bound into HIV-1 protease was obtained (Figure 15). The general core interactions were consistent with those found in the coumarin X-ray and the dihydropyrone model. The presence of electron density in both S and S2 indicates a mixed population for the thiophenethyl group between the two pockets. It was hoped that only the more potent enantiomer would be bound in the active site but the X-ray indicated that both enantiomers of 44b were present. Therefore, an accurate determination of the preference for the phenyl and n-pentyl groups to reside in St or S2 could not be obtained from the electron density. What is clear is that the substituents (phenyl and n-pentyl) fill both S2 and Sp thus increasing the potency of these... 

For example, simple fluorescence intensity measurements on dispersed hydrocarbon probes such as anthracene [17], perylene [18], pyrene [6,17,22], 9,10-dimethylanthracene (DMA) [60], and coumarin dyes [62] have confirmed that PMAA displays pH-dependent solution behavior. A marked decrease in the intensity of the probe occurs between pH 5 and 6, which coincides with the conformational transition of PMAA as determined by classical methods [2-4,47-50]. Two interrelated effects account for this behavior the solubilizing capacity of the polymer promotes an increase in the concentration of the probe in the solution [6,17,18,60,62] and because the intensity of the fluorescence observed is proportional to the excited state population the resulting emission is enhanced. The hydrocarbons may also be considered to be preferentially solubilized within the hydrophobic domains or structures of the hypercoiled state [6,22]. This results in a degree of protection from the deactivating effects of the aqueous phase and a concomitant increase in the fluorescence observed [6,17,18,22,60,62]. 

Scheme 8. Enantioselective Photoreactions in TADDOL Inclusion Compounds with a Cou-marin, a Methacryl Anilide, and an Oxocyclohexenyl-carboxamide. In the first case, the packing of the coumarin molecules in the mixed crystal is such that the double bonds are predisposed for the (2+2) cycloaddition. In the second example, a photochemical electrocychc reaction is followed by a sigmatropic H shift. The third reaction is an intramolecular (2+2) cycloaddition with dia- and enantioselective formation of three new stereogenic centers. There are several more reactions of this type, described in the literature [54], and the Toda group has determined the crystal structures of a number of inclusion compounds to show the correlation between the crystal packing and the configuration of the photoproducts. EMastereoselective solid-phase reactions of chiral guests in TADDOL-host lattices have also been described by the...

As noted above, PC is the by far most frequently investigated phospholipid [40, 82, 83], and consequently was one of the first PLs to be studied using MALDI-TOF-MS [46, 75]. As the pioneer in this field, Harvey [46] investigated, as early as 1995, a variety of PLs to determine which matrix would provide the best spectral quality. Among other matrices, a-cyano-4-hydroxycinnamic acid, 6,7-dihydroxy-coumarin and DH B gave the best results. Today, DHB is the most frequently used matrix for lipid analysis by MALDI-MS, and is regarded as the work horse of the field because essentially all Hpids-irrespective of their structure-are detectable with DH B. A comprehensive list of usefijl matrices for the lipid field is available in Refs [41] and [84]. 

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