Exciton-chirality method

The configuration of the 4R,5R-dihydrodiol was established by application of the exciton chirality method (6). To minimize undesired interactions between the electric transition dipoles of the two j>-N,N-dimethylaminobenzoate chromophores and the dihydrodiol chromo-phore, a 4,5-dihydrodiol enantiomer was first reduced to 1,2,3,3a,4,5,7,8,9,10-decahydro and 4,5,7,8,9,10,11,12-octahydro derivatives (6). We found that it is not necessary to reduce the chrysene chromophore of a BaP 4,5-dihydrodiol enantiomer (Figure 2). Similarly, the absolute configurations of the K-region dihydrodiol enantiomers of BA (7), 7-bromo-BA (8), 7-fluoro-BA (9), 7-methyl-BA (10). and 7,12-dime thy 1-BA (DMBA) (7 ) can also be determined by the exciton chirality method without further reduction. 

The absolute configuration of the 7,8-dihydrodiol metabolite was also established to be 7R,8R by the exciton chirality method (11.12), Our result (Figure 2) is in agreement with those reported earlier (11.12). 

The absolute configuration of the 9,10-dihydrodiol metabolite was established to be 9R,10R both by nuclear magnetic resonance spectroscopy and by the structures of the hydrolysis products formed from the svn and anti 9,10-dihydrodio 1-7,8-epoxides which were synthesized from the same 9,10-dihydrodiol enantiomer (13). The absolute configuration of a BaP trans-9.10-dihvdrodiol enantiomer, after conversion to a tetrahydro product, can also be determined by the exciton chirality method (Figure 2) (19.20). 

Harada N, Nakanishi K, Exciton chirality method and its application to configurational and conformational studies of natural products, Accounts Chem Res 5 257-263, 1972. 

The Cotton effects may be classified into three types168 those arising from chirally perturbed local achiral chromophores (ketones, /i.y-unsaturated ketones, double bonds, benzoates, aromatic compounds) those arising from inherently achiral chromophores, such as conjugated dienes or a,/3-unsaturated ketones those arising from interaction of the various electric transition moments when two or more chromophores which are chirally disposed are positioned nearby in space, intra- or intermolecularly (exciton chirality method)169. 

In special cases of nonracemic compounds, both relative and absolute configuration can be determined by means of circular dichroism. Thus, the relative and absolute configurations of acyclic 1.2-, 1,2,3-, 1,2,3,4-, and 1,2,3,4,5-polyols can be determined by the bichromophoric exciton chirality method after a two-step derivatization [primary and secondary hydroxy groups are selectively esterified with 9-anthroyl chloride (2) and ( )-3-(4-methoxyphenyl)-2-propenoyl chloride (4), respectively] and comparison of the CD curves with references curves265. 

For example, compounds 5 obtained from 1,2,3-triols of type 1 provide CD spectra which distinguish characteristically and predictably between stereoisomers (bichromophoric exciton chirality method). Thus, relative and absolute configuration of such 1,2,3-triols can be deduced from a single measurement180. 

The following discussion is divided into three subsections the ketone chromophore (Section 4.4,1.1.), for which configurational assignments are based on the effect of ring dissymmetry and substitution pattern on the rotatory power of the n-rt transition. For conjugated chro-mophores (Section 4.4.1.2.) it is both the helicity of the chromophore and the vicinal substituent effect that determines the rotatory power of the 71-71 transition. Finally, the versatile stereochemical method, exciton chirality method (Section 4.4.2.), is based on the chiral interaction between the electric dipoles of the allowed transitions in two or more chromophores. 

Many chromophores are suitable for use in the exciton chirality method. One of the features required for such a chromophore is its planarity or near-planarity. Nonplanar (inherently dissymmetric) chromophores would contribute to the CD spectra by other mechanisms. The other limiting factor is the position of the transition in the spectral region studied. For example, the 1B transition in the alkyl-substituted benzene chromophore appears near the short-wavelength recording limit around 200 nm, making its use in the exciton chirality method less attractive. Furthermore, the direction of polarization of the lB transition in alkyl-substituted benzene derivatives is not readily determined. In such cases calculation of the rotatory strength is more reliable than qualitative analysis. 

Table 7 lists some of the most common chromophores used in stereochemical studies by the exciton chirality method. 

Table 7. Chromophores and Polarization of Transitions Useful for Application in the Exciton Chirality Method...

The power of the exciton chirality method lies in its applicability to molecules having functional groups which are not chromophores in the usual sense (such as hydroxy, amino or thiol groups), but can be converted to a chromophoric derivative, such as an unsaturated or aromatic acyl derivative. This procedure is extremely useful for the determination of the absolute configuration of products of stereoselective synthesis having a hydroxy, amino or thiol group at the stereogenic center. 

The dibenzoate chirality rule 155, 156 extends the application of the exciton chirality method to molecules containing no suitable chromophore, but, rather two hydroxy groups which can be converted to benzoates or cinnamates. For example, the dibenzoate 1, obtained by benzoy-lation of the ra-diol, from microbial oxidation of ethylbenzene, displays a negative exciton Cotton effect and is hence assigned the 1 S.2R configuration157. 

The absolute configuration of a molecule bearing three or more hydroxy groups attached to the acyclic skeleton can also be determined in a nonempirical way through application of the exciton chirality method. The amplitude of the polybenzoate exciton Cotton effect is a sum of amplitudes of Cotton effects of the component pairs of benzoates. This additivity relationship allows characterization of pyranoses through their 4-bromobenzoate exciton Cotton effects168 (Figure 20). 

The secondary structure of poly(iV-alkynylamides) is influenced by the position of the chiral center and amide group.The position of the chiral center mainly affects the helical pitch, which becomes short when the chiral center is positioned away from the main chain. The stability of the helical structure is also influenced by the position of the amide group. Based on molecular orbital study, it is concluded that poly(iV-propargylamides) with right-handed helical structure display a plus Cotton effect around 390 nm. This is also confirmed by the exciton chirality method using porphyrin as a chromophore. ... 

The absolute stereochemistry of forskolin (45) and of the C(6) and C(j) dibenzoyl derivative (46) was unequivocally assigned by applying the exciton chirality method, thus placing R3 (OAc in 45) substituent at -position134. 

The absolute configuration of Wieland-Miescher ketone analogues bearing an angular protected hydroxymethyl group was unambiguously determined after regio- and stereoselective reduction of the saturated ketone function to cis -alcohols and application of the exciton chirality method to bicyclic enone-benzoate chromophoric systems 155-158352. 

The (4R)-absolute configuration of a new chromophore of native visual pigment (159) (negative Cotton effect at 375 nm, negative Cotton effect at 254 nm) was established by the CD exciton chirality method applied to the 4-(dimethylamino)cinnamate (160). The split negative (381 nm) and positive (338 nm) exciton effects of 160 show a counterclockwise helicity between pentaenal and a-4-(dimethylamino)cinnamate chromophores355. 

The experimental CD spectra of these donor-acceptor cyclophanes were very well reproduced by the theoretical calculations at the TD-DFT-BH-LYP/TZV2P level [32]. The amount of the exact exchange in the functional to be used turned out to be important for better agreement with experiment. The analysis of the configuration contributions showed that the observed CD spectra essentially resulted from simple overlap of the Cotton effects of pure n-n transitions in the donor and acceptor parts, in addition to the CT transitions. Thus, the exciton chirality method cannot be applied to the absolute configuration determination for these cyclophanes. The experimental CD spectrum of more congested donor-acceptor cyclophane 22 was reproduced in a less satisfactory manner compared to the cases of 20 and 21. The absolute configuration was safely determined by a comparison of the experimental spectrum with the theoretical data at the TD-DFT level however, the satisfactory reproduction of the whole CD spectrum of 22 was only possible by... 

Furo T, Mori T, Wada T, Inoue Y (2005) Absolute configuration of Chiral [2.2]paracyclo-phanes with intramolecular charge-transfer interaction. Failure of the exciton chirality method and use of the sector rule applied to the cotton effect of the CT transition. J Am Chem Soc 127 7995-8006 and 1638... 

Figure 26. Exciton chirality method for the determination of the absolute configuration of steroidal diols. The clockwise (+) and counterclockwise (-) directionality of two dipoles is determined by the configuration of the diol.

Picrodendrins E (65) and F (66) more closely resemble pretoxin (59) and dendro-toxin (60) (55). X-ray analysis of the monobromobenzoate of picrodendrin F (66) was impeded by the fact that the two molecules of the asymmetric unit have different conformations. However, it was possible to determine the relative conhg-uration of the stereogenic centers. The CD exciton chirality method conducted on the 16,18-bisbromobenzoate of picrodendrin F (66) revealed its absolute conhgu-ration. Comparison of the spectra of picrodendrin F (66) and of pretoxin (59) with those of picrodendrin E (65) allowed the determination of its stmcture. Shifts and... 

For the description of the CD spectra of molecules with two (or more) identical or at least similar chromophores in a chiral arrangement the method of coupled oscillators (exciton chirality method) has proven particularly successful. Such systems can occur either as chiral dimers, or they can be obtained by introducing suitable chromophores into a chiral molecule. The best-known example is given by the dibenzoates derived from 1,2-cyclo-hexanediol of the general formula 4 ... 

Specific optical rotation, circular dichroism (CD), and the newly developed exciton chirality method [96] for functionalized carbohydrates bearing specific chromophores are particularly... 

To determine the absolute configuration of optically active organic compounds, there are two nonempirical methods. One is the Bijvoet method in the X-ray crystallographic structure analysis, which is based on the anomalous dispersion effect of heavy atoms. - The X-ray Bijvoet method has been extensively applied to various chiral organic compounds since Bijvoet first succeeded in determination of the absolute stereochemistry of tartaric acid in 1951. The second method is a newer one based on the circular dichroism (CD) spectroscopy. Harada and Nakanishi have developed the CD dibenzoate chirality rule, a powerful method for determination of the absolute configuration of glycols, which was later generalized as the CD exciton chirality method. 8 The absolute stereochemistry of various natural products has been determined by application of this nonempirical method. 

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