Chiral specificity

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

In addition, three types of lipophilic conjugates have been found in pyrethroid metabolism studies (Fig. 4). They are cholesterol ester (fenvalerate) [15], glyceride (3-PBacid, a common metabolite of several pyrethroids) [16], and bile acid conjugates (fluvalinate) [17]. It is noteworthy that one isomer out of the four chiral isomers of fenvalerate yields a cholesterol ester conjugate from its acid moiety [15]. This chiral-specific formation of the cholesterol ester has been demonstrated to be mediated by transesterification reactions of carboxylesterase(s) in microsomes, not by any of the three known biosynthetic pathways of endogenous cholesterol esters... 

Table 19 reports multicollisional dissociation thresholds of the selected complexes. A direct correlation exists between them and the proton affinity (PA) of the guest. However, although chiral specificity has been observed in similar systems using ligand-exchange reactions (see previous sections), the results of Table 19 show no such specificity. The differences in binding of the Ala and Phe enantiomers are evidently too small to be measured with this method. 

Shafiee, A., Motamedi, H. and King, A., Purification, characterization and immobilization of an NADPH-dependent enzyme involved in the chiral specific reduction of the keto ester M, an intermediate in the s3mthesis of an anti-asthma drug, montelukast, from Microbacterium campoquemadoensis (MB5614). App/. Microbiol. Biotechnol., 1998, 49, 709-717. 

In this model we can pick out the chain of six carbon atoms, numbered 1-6, of which five carry OH groups. So each of these carbon atoms carries the functional group characteristic of alcohols. Note that five of the carbon atoms are chiral. Specifically, carbons 1-5 all possess four distinct substituents and are, therefore, chiral. Finally, note that carbon-1 is linked to two oxygen atoms, one in the hydroxyl group and the one in the ring. 

A large proportion of NCEs will have one or more chiral centres. Only single enantiomers can be used nowadays, whereas previously a racemic mixture would have been tested. Different enantiomers produce different pharmacological responses, with one enantiomer usually being more active by at least an order of magnitude. There has been considerable debate on the administration of racemates versus the single active enantiomer or eutomer however, the current trend is to develop only the active optical isomer. The synthetic route employed will, if required, have to utilise chiral-specific reagents and catalysts or the compound will have to be purified after synthesis. With this type of compound, an additional specification or limit is required for the presence of the inactive enantiomer. ... 

If there are chiral centers, are the bioactivities chiral specific ... 

Hobson K. R., Wood D. L., Cool L. G., White P. M., Ohtsuka T., Kubo I. and Zavarin E. (1993) Chiral specificity in responses by the bark beetle Dendroctonus valens to host kairomones. J. Chem. Ecol. 19, 1837-1846. 

There are three possible approaches to the separation of chiral species by CE (1) addition of chiral selectors to the buffer, (2) use of a chiral stationary phase, and (3) precolumn derivatization. These correspond to the approaches in HPLC, and the separation mechanisms are described in Section 2.8. In the first approach, additives are added to CZE, CGE, or MECC buffers to effect the separation. In the second approach, chiral selectors can be immobilized on the capillary wall, although that is a difficult process. Alternatively, capillaries filled with enantiospecific packings can be employed for CEC. In the third approach, enantiomers are derivatized with chirally specific reagents prior to CZE or MECC. Addition of chiral selectors to the buffer is the most common approach. 

Isomerism (chiral) The most common type of chirality in biochemistry is tetrahedral. The tetrahedral chiral specification ( or ) is written as an atomic property following the atomic symbol of the chiral atom. Looking at the chiral center from the direction of the from atom (preceding the chiral atom), (or 1) means the other three atoms (following the chiral atom) are listed anti-clockwise (or 2) means clockwise. If the chiral atom has a nonexplicit hydrogen, it will be listed inside the chiral atom s brackets as [C H]—for example,... 

Fig. 3.4.4. Reciprocal chiral specificity. (A) The selected d-RNA sequence (aptamer) binds to the unnatural synthetic L-adenosine but not to D-adenosine and the corresponding l-RNA sequence (spiegelmer) recognizes naturally occurring D-adenosine but not L-adenosine. (B) The non-cognate interactions are approx. 9000-fold weaker than the intended interactions. (C)...

Some of the aggregation pheromones of scolytid beetles also appear to be synthesized with great chiral specificity. The flight response of both sexes of the western pine beetle Dendroctonus brevicomis to (lR,5S,7R)-(+)-exo-brevicomin (XX), host terpenes, and racemic frontal in (XXI) was much greater than the response when the antipode of brevicomin was substituted (160). Similarly, (lS,5R)-(-)-frontalin was a much more powerful attractant than its antipode when tested in admixture with... 

These results clearly demonstrate that insects possess chiral chemoreceptors which have enabled them to exploit chemical signals with maximum acuity and sensitivity. It is probable that the olfactory world of insects will be found to be characterized by a diversity of chiral specificities which have maximized their responsiveness as targets for enantiomeric signal molecules. 

Abstract Understanding the origin of chirality in nature has been an active area of research since the time of Pasteur. In this chapter we examine one possible route by which this asymmetry could have arisen, namely chiral-specific chemistry induced by spin-polarized electrons. The various sources of spin-polarized electrons (parity violation, photoemission, and secondary processes) are discussed. Experiments aimed at exploring these interactions are reviewed starting with those based on the Vester-Ulbricht hypothesis through recent studies of spin polarized secondary electrons from a magnetic substrate. We will conclude with a discussion of possible new avenues of research that could impact this area. 

Chiral-specific photochemistry using CPL depends on the circular dichroism (A = r l) of the reactants, i.e., the differences in the absorption coefficients or right and left CPL. The rate of the reaction depends on the amount of light absorbed so if A > 0, there will be a bias towards one of the enantiomers leading either to its preferential enhancement or destruction and an ee The enantiomeric purity of the chiral product is determined by the anisotropy factor, g, where g - A / and = 0.5( r+ l). For optically active compounds g values are fairly small, 0.01. 

The possible role of SEs in conjunction with the above high energy polarized electron experiments was first noted by Walker. He pointed out that any chiral effects of the high energy electrons would be seriously diluted by the unpolarized SEs produced in the samples [84]. Subsequent years saw the research into electron-induced chiral-specific reactions shift to the use of low energy electrons. 

In contrast, liquid chromatography lends itself to chiral separations and there are two basic procedures for separating optically active solutes. Firstly, reversed phase chromatography can be employed and a chiral substance can be added at low concentrations in the mobile phase. The chiral additive will be absorbed onto the surface of the reversed phase and act as an adsorbed stationary phase having chiral activity. This approach makes chiral detection more difficult, as it provides a background of optical activity in the mobile phase that will be many orders greater than that from the chirally active solutes. This is inevitably accompanied by a high noise level and consequent poor sensitivity. The second approach is to employ specific chirally active materials that are bonded to a silica or polymer surface to provide chirally specific interactions with the solutes. 

Parity, or space inversion, is the symmetry operation that interconverts a chiral molecule into its mirror image. All coordinates (x, v, <) are replaced everywhere by (—X, — y, —z) under space inversion [2]. A chirality specific response in liquids and gases requires that the isotropic component of the susceptibility is odd under parity. Further, since the isotropic part of any tensor is necessarily a scalar, it follows that pseudoscalars - independent of the choice of coordinate axes and of opposite sign for enantiomers - underlie chiral observables in fluids. The isotropic medium may... 

Table 1.. Some chirality. specific susceptibilities in fluids and the operators that enter the numerator of the corresponding quantum mechanical expressions...

Figure 7. Dispersion of the chirality specific (chiral) pseudoscalar relative to for the SFG process in optically active l,l -bi-2-naphthol. Configuration Interaction Singles SOS calculation with the cc-pVDZ basis, damping = 3000 cm...

Symmetry arguments show that parity-odd, time-even molecular properties which have a non-vanishing isotropic part underlie chirality specific experiments in liquids. In linear optics it is the isotropic part of the optical rotation tensor, G, that gives rise to optical rotation and vibrational optical activity. Pseudoscalars can also arise in nonlinear optics. Similar to tlie optical rotation tensor, the odd-order susceptibilities require magnetic-dipole (electric-quadrupole) transitions to be chirally sensitive. 

At the synthetic level we may expect increased emphasis on enantioselective catalysis usin metal complex catalysts as a key component of the manufacturing process (84). For biocatalysts there will unquestionably continue to be increasing interest in the "custom synthesis" of enzymes engineered for specific functions and conditions. The first example of the "ultimate" enzyme has been reported with the synthesis of the all-D form of HIV-1 protease (85-87). This enzyme exhibits a chiral specificity opposite to that of the naturally occurring L form and it may be generally predicted that enantiomeric proteins will exhibit reciprocal chiral specificity in all aspects of their interactions. These reciprocal chiral... 

Chiral chromatography16 For the separation of enantiomers using a chiral-specific stationary phase. Both NPC and RPC chiral columns are available. 

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