CD exciton chirality method

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. 

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... 

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. 

In addition to the CD exciton chirality method, we have recently reported that the theoretical calculation of the CD spectra by the jt-electron SCF-CI-dipole velocity MO method8-l4 has become an important tool for determination of the absolute configuration of a variety of twisted and conjugated n-electron systems. In fact, we have recently determined the absolute stereochemistry of (8aS)-(+)-l,8a-dihydro-3,8-dimethylazulene 10, a labile biosynthetic intermediate for 1,4-dimethylazulene 11 isolated from a liverwort, by application of the MO method to the theoretical calculation of the CD spectra of the twisted tetraene system (8a/ )-12.15 In that case, we have also succeeded in the experimental verification of the absolute configuration theoretically determined, by comparison of the CD spectra of the natural product with those of synthetic chiral model compounds (8a5)-(+)-... 

The CD exciton chirality method has been extensively applied to degenerate systems consisting of two identical chromophores such as dibenzoate, bis(naph-thalene), and bis(anthracene) compounds.8 In addition to such degenerate systems, the CD exciton chirality method is also useful for determination of the absolute stereochemistry of non-degenerate systems which contain two different chromophores. For example, Harada and Nakanishi determined the absolute configuration... 

The CD exciton chirality method is very powerful for the determination of the absolute stereochemistry of chiral organic compounds. To confirm the absolute... 

Substituted benzene and polyacene chromophores for the CD exciton chirality method 106... 

Determination of Absolute Configuration by the CD Exciton Chirality Method 120... 

Application of the CD exciton chirality method to acyclic 1,2-glycols 120... 

CD exciton chirality method 11 the most simple and reliable method applicable to a variety of natural products, because the exciton-coupled CD is based on the coupled oscillator theory and the mechanism of this method has already been established as will be briefly explained in the following sections. Therefore, numerical calculations using a computer are not necessary. 

The CD exciton chirality method has been successfully applied to a variety of natural products to determine their ACs. This method enables one to deduce the AC of a chiral compound without any reference compound, and therefore, it is established as a nonempirical method. The principles of the CD exciton chirality method are explained using the steroidal bis(p-dimethylaminobenzoate) shown below as a model compound, where the nonempirical nature of this method is easily proved.8 11 1... 

Figure 8 Application of the CD exciton chirality method to cholest-5-ene-3/3,4/3-diol bis(p-dimethylaminobenzoate) 1 CD and UV spectra in EtOH. Redrawn from N. Harada K. Nakanishi, Circular Dichroic Spectroscopy - Exciton Coupling in Organic Stereochemistry, University Science Books Mill Valley, CA, and Oxford University Press Oxford, 1983.

The Consistency between X-Ray Crystallographic Bijvoet and CD Exciton Chirality Methods... 

As discussed above, the CD exciton chirality method enables one to determine ACs in a nonempirical manner. A striking example proving the nonempirical nature and utility of the CD exciton chirality method is the reversal of the ACs of clerodin 7 and related diterpenes 8, 9 as briefly explained below (Figure 12). 

However, the observed positive exciton couplet of 3,6-bis(/>-Cl-benzoate) 11 derived from 3-epicaryoptin 9 disagreed with the negative one expected from the ACs of 11 and 11a (Figure 12). To explain the discrepancy between the CD and AC, the conformation 1 lb was proposed in which one of the benzoate groups adopted a twisted conformation due to an intramolecular hydrogen bond (H-bond), thus generating a positive twist (Figure 12). This result was reported as an exception of the CD exciton chirality method.34... 

As described above, 3,6-bis(/ -Cl-benzoate) 11 was reported as the exception of the CD exciton chirality method. To resolve this problem, in 1978 the steroidal model compound 12 was synthesized.38 Compounds 12 and 11 have the same relative configurations at key positions as shown in 12a and 11a (Figure 13). The CD spectrum of 12 showed a positive couplet in agreement with the positive twist of conformation 12a, indicating that the conformation of the benzoate group is not twisted by an intramolecular H-bond. Since 3,6-bis(/>-Cl-benzoate) 11 and 12 showed CD couplets of the same sign, 11a should have the same AC as 12a as shown in Figure 13. From these results, the ACs of 11, 9, and 7 were reversed.38... 

As demonstrated in Section 9.04.4.2, the transition of polyacene chromophores is ideally suitable for observing exciton-coupled CD. The UV data of some polyacenes with D2h-symmetry are shown in Figure 14. In the polyacene systems, there is no ambiguity for determining the long and short axes, and therefore the CD exciton chirality method offers more reliable and definite conclusions of AC. 

The conjugated dienes, enones, etc., shown in Figure 14 are useful chromophores for the CD exciton chirality method. The transition moment of their 7t—7t band is almost parallel to the long axis of the chromophores as depicted in the tables. 

The chromophores used for the CD exciton chirality method have to satisfy the following requirements (1) presence of an intense tt—tt transition and (2) direction of the transition moment is clear in the geometry of the chromophore. Therefore, in general, chromophores of high symmetry are desirable. 

As discussed in the above examples of natural products, the intramolecular CT or La transition (230-310nm) of /wra-substituted benzoate chromophores is useful for determining the AC of glycols.8 The intramolecular CT transition is polarized along the long axis of the benzoate chromophore, which is almost parallel to the alcoholic C-0 bond. Therefore, the AC of the glycol part can be determined from the exciton CD data. On the other hand, ortho- and mcto-substituted benzoate chromophores are not suitable for the CD exciton chirality method because their transition moments are not parallel to the alcoholic C-0 bond. 

Figure 16 Typical chromophores useful for the CD exciton chirality method, where arrows show the direction of transition moment responsible for the exciton-coupled CD.

The CD exciton chirality method is also applicable to the intramolecular CT band of benzamido groups. The transition is polarized along the long axis of the chromophore. However, in some cases, the benzamide moiety exists as a mixture of (E) and (Z) isomers, and therefore, the mutual orientation of the transition moments is uncertain. Thus, in these situations, one should be cautious in assigning AC by CD. 

The chromophore of 2,3-naphthalenedicarboximide exhibits an intense Bb transition around 260 nm, which is polarized along the long axis of the chromophore. This C2v-symmetrical chromophore is ideally suitable for the CD exciton chirality method because the long-axis-polarized transition moment is exactly parallel to the C—N bond of amine moiety. This is an advantage of the 2,3-naphthalenedicarboximide group and hence the use of this chromophore is highly recommended for primary amines. 

As discussed above, CD spectroscopy is useful for the characterization of natural products. In the following, the application of CD spectroscopy to the structural studies of natural products is exemplified and explained. The cases are (1) CD and solvent-dependent conformational change, (2) determination of AC by comparison of CD spectra, (3) application of CD exciton chirality method, (4) CD of atropisomers, (5) determination of ACs by theoretical calculation of CD spectra, and (6) supramolecular systems and CD spectra. 

To determine the ACs of acyclic 1,2-glycols, the CD exciton chirality method has been applied to their dibenzoates or bis(2-anthroates), which show typical bisignate Cotton effects (see Section 9.04.4) as exemplified in Figures 27 and 28.72,73 Acyclic dibenzoates or bis(2-anthroates) can rotate around the bond connecting two benzoate or 2-anthroate chromophores, and therefore the CD sign depends on the conformational equilibrium. From the data of many examples, general rules were derived as shown in Figures 27 and 28. 

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