Predictability of Enantioselectivity

This theoretical receptor that considers neurotensin as part of the DA receptor accommodates DA agonists and antagonists of diverse structure (116). It Is suited to the dopaminergic 3-ben-zazepines, but it is not predictive of enantioselectivity. 

Caetano, S., Aires-de-Sousa, J., Daszykowski, M. and Vander Heyden, Y. (2005) Prediction of enantioselectivity using chirality codes and classification and regression trees. Anal. Chim. Acta, 544, 315-326. 

The excellent agreement between the experimental data and the proposed model fit shown in Figures 1 and 2 reveal the power of this simple two-step mechanism in rationalizing complex (and heretofore inexplicable) observed relationships between reaction variables. Further support for this model comes from its prediction of enantioselectivities at pressures outside the range used in its development, corroborated by independent experimental data. 

Within these general terms, the interpretation and prediction of enantioselectivity depends on the binding of the particular reactant in the catalyst pocket. A wide range... 

Darcel C, Moulin D, Henry JC, Lagrelette M, Richard P, Harvey PD, Juge S (2007) Modular F-chirogenic aminophosphane-phosphinite ligands for Rh-catalyzed asymmetric hydrogenation a new model for prediction of enantioselectivity. Eur J Org Chem 13 2078-2090... 

Computational Calculations Determination and/or Prediction of Enantioselectivity of Syndiospecific... 

Haeffner F, Norm T. 1999. Molecular modeling of lipase-catalyzed reactions. Prediction of enantioselectivity. Chem Pharm Bull 47 591-600. 

The molecular modeling methods have limited value as a general tool in prediction of enantioselectivity. However, it is expected that their usefulness will increase as modeling algorithms and computing facilities get better. Probably rational design of enantioselective syntheses will in the future be based on known enzyme structures. 

Lipase catalysis is a very diverse and broad field where, still, little is known about lipase mechanisms on a molecular level. The extensive research currently going on is expected to reveal important information regarding the controlled tailoring of lipase en-antioselectivity. Important aspects other than steric effects are the involvement of water, the nature of die solvent, and the enhropic influence on substrate binding and transition state stabilization. This knowledge will provide an understanding of tiie details of lipase catalysis and facilitate the development of quantitative computer models for prediction of enantioselectivity in the very near future. 

In chemoinformatics, chirality is taken into account by many structural representation schemes, in order that a specific enantiomer can be imambiguously specified. A challenging task is the automatic detection of chirality in a molecular structure, which was solved for the case of chiral atoms, but not for chirality arising from other stereogenic units. Beyond labeling, quantitative descriptors of molecular chirahty are required for the prediction of chiral properties such as biological activity or enantioselectivity in chemical reactions) from the molecular structure. These descriptors, and how chemoinformatics can be used to automatically detect, specify, and represent molecular chirality, are described in more detail in Chapter 8. 

The chiral center in 2-butyl bromide is created when Br adds to 2-butyl cation. The key, then, is to predict the enantioselectivity of this step. 2-Butyl cation exists as a mixture of three conformers planar, perpendicular A, and perpendicular B. Compare their energies and use equation (1) to calculate the relative amounts of each conformer at 298 K. Should all three conformers participate in the reaction to a significant extent ... 

Methanol remains the most widely used modifier because it produces highly efficient separations, but it does not always produce the highest selectivity [8]. Recent studies have provided insight into the role of the modifier in enantioselectivity in SFC [69]. Blackwell and Stringham examined a series of phenylalanine analogues on a brush-type CSP and developed a model that allowed prediction of selectivity based on the bulk solvation parameters of various modifiers [70]. Careful choice of modifiers can be used to mask or enhance particular molecular interactions and ultimately provide control of selectivity [71]. 

The tertiary structure of glutamate racemase has already been resolved and it has also been shown that a substrate analog glutamine binds between two cysteine residues. These data enabled us to predict that the new proton-donating amino acid residue should be introduced at position 74 instead of Gly for the inversion of enantioselectivity of the decarboxylation reaction. 

The interpretation and prediction of the relationship between the configuration of the newly formed chiral center and the configuration of the amine are usually based on steric differentiation of the two faces of the imine anion. Most imine anions that show high stereoselectivity incorporate a substituent which can hold the metal cation in a compact transition state by chelation. In the case of entry 2 in Table 1.3, for example, the observed enantioselectivity is rationalized on the basis of transition state L. 

The usefulness of protein-type CSPs has already been shown in particular Chiral-AOP and Ultron ES-OVM (see Table 2) have a very broad range of enantioselectivity. It is not, however, possible to systematically predict the resolution on such CSPs, but the overall retention, selectivity and efficiency can be modified to a certain extent by altering several key variables ... 

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