Chiral materials

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

The main strategy for catalytic enantioselective cycloaddition reactions of carbonyl compounds is the use of a chiral Lewis acid catalyst. This approach is probably the most efficient and economic way to effect an enantioselective reaction, because it allows the direct formation of chiral compounds from achiral substrates under mild conditions and requires a sub-stoichiometric amount of chiral material. 

A large number of the organic compounds in food and beverages are chiral molecules. In addition, a significant number of the additives, flavours, fragrances, pesticides and preservatives that are used in the food industry are also chiral materials. 

Extension of this aldol reactivity to the preparation of chiral materials via condensation reactions of the chiral enolate species 2 and 3 is discussed in the following sections. 

For generic bioequivalence the generic manufacturer would be expected to use the same chiral material as the innovator (most probably a racemic mixture or pure active isomer, though it is possible that in some rare instances the innovator might have discovered a valid reason for using some mixture of R and S other than 50/50). Thus, as with development bioequivalency, it would not normally seem necessary to use stereoselective assays for the separate determination of R and S isomers. However, one can conceive of possible situations where clinically significant differences in R-to-S ratios could be caused by even relatively small differences in absorption rate [6,7]. 

The above results are valuable in that an optically active compound is produced in bulk from achiral material. Only a few successful examples of photochemical conversion of achiral into chiral material in the absence of a chiral source have been reported hitherto 49, and in these cases the conversion was carried out on a fragment of a chiral crystal. In our case, chiral crystals are available in bulk, and mass production of the chiral compound is possible. 

There are two reasons to think this situation might occur. The first reason is experimental. As discussed in Sections 2-5, in most experiments on chiral materials, tubules and helical ribbons are observed with only one sense of handedness. However, there are a few exceptions in experiments on diacetylenic phospholipids,144 diacetylenic phosphonate lipids,145 146 and bile.162 In these exceptional cases, some helices are observed with the opposite sense of handedness from the majority. In the work on diacetylenic phospholipids, the minority handedness was observed only during the kinetic process of tubule formation at high lipid concentration,144 which is a condition that should promote metastable states. Hence, these experiments may indeed show a case of biased chiral symmetry-breaking in which the molecular chirality favors a state of one handedness and disfavors a mirror image state. 

Chiral Materials for Second-Order Nonlinear Optical Applications... 

The study of chiral materials with nonlinear optical properties might lead to new insights to design completely new materials for applications in the field of nonlinear optics and photonics. For example, we showed that chiral supramolecular organization can significantly enhance the second-order nonlinear optical response of materials and that magnetic contributions to the nonlinearity can further optimize the second-order nonlinearity. Again, a clear relationship between molecular structure, chirality, and nonlinearity is needed to fully exploit the properties of chiral materials in nonlinear optics. 

Nonlinear optical techniques are extremely useful in characterizing the chiral properties of materials, as is pointed out by Verbiest and Persoons in Chapter 9. These authors give an in-depth discussion of this tool, both from an experimental and theoretical point of view, paying special attention to the characterization of chiral surfaces and thin films. In the second part of their contribution they highlight the role chiral materials can play in the field of nonlinear optics and photonics, which opens the way for a variety of applications. 

Hydride reductions of C = N groups are well known in organic chemistry. It was therefore obvious to try to use chiral auxiliaries in order to render the reducing agent enantioselective [88]. The chiral catalyst is prepared by addition of a chiral diol or amino alcohol, and the active species is formed by reaction of OH or NH groups of the chiral auxiliary with the metal hydride. A major drawback of most hydride reduction methods is the fact that stoichiometric or higher amounts of chiral material are needed and that the hydrolyzed borates and aluminates must be disposed of, which leads to increased costs for the reduction step. 

Figure 1-12. Basic structures of chiral materials used as the stationary phase in gas chromatographic resolution via hydrogen bonding.

The reasons for the increasing acceptance of enzymes as reagents rest on the advantages gained from utilizing them in organic synthesis Isolated or wholecell enzymes are efficient catalysts under mild conditions. Since enzymes are chiral materials, optically active molecules may be produced from prochiral or racemic substrates by catalytic asymmetric induction or kinetic resolution. Moreover, these biocatalysts may perform transformations, which are difficult to emulate by transition-metal catalysts, and they are environmentally more acceptable than metal complexes. 

These compounds derived from 3-acetylthiazolidine-2-thione are very versatile chiral materials, capable of being transformed into various synthetic intermediates as previously demonstrated (30). Furthermore, in the stannous enolate mediated aldol-type reactions of 3-(2-benzyloxyacetyl)thiazolidine-2-thione, the stereochemical course of the reaction is dramatically altered by the addition of TMEDA as a ligand. High asymmetric induction is also achieved by the addition of a chiral diamine derived from (S)-proline (31). 

Chromatographic Techniques. If a chromatographic column consists of a chiral substance, it may be possible to resolve a racemic mixture. This is a very useful protocol and several chiral materials are now commercially available. 

Note 6 Chiral materials form chiral smectic F mesophases denoted by SmF. ... 

In practice, any of these four approaches might be the most effective for a given synthesis. If they are judged on the basis of absolute efficiency in the use of chiral material, the ranking is resolution < natural source < chiral auxiliary < enantioselective catalyst. A resolution process inherently employs only half of the original racemic material. A starting material from a natural source can, in principle, be used with 100% efficiency, but it is consumed and cannot be reused. A chiral auxiliary can, in principle, be recovered and reused, but it must be used in stoichiometric amount. A chiral catalyst can, in principle, produce an unlimited amount of an enantiomerically pure material. 

Amphetamine (1) is a very simple phenethylamine, described in the chemical literature as early as 1887 (Edeleano, 1887). Smith, Kline and French (now GSK) filed a patent on the synthesis and use of amphetamine in 1930 (Nabenhauer, 1930), and the enantiomers were assigned in 1932 (Leithe, 1932 V-Braun and Friehmelt, 1933). Not surprisingly, early access to chiral material relied on classical crystallization-based resolutions (Gillingham, 1962 Nabenhaur, 1942). The early, racemic syntheses of amphetamine fall into four major classifications according to the method used to make the C-N bond ... 

In order to place later chapters in proper context, the first chapter offers a comprehensive overview of industrially important catalysts for oxidation and reduction reactions. Chapters 2 and 3 describe the preparation of chiral materials by way of the asymmetric reduction of alkenes and ketones respectively. These two areas have enjoyed a significant amount of attention in recent years. Optically active amines can be prepared by imine reduction using chiral catalysts, as featured in Chapter 4, which also discloses a novel reductive amination protocol. 

Progress has also been made in asymmetric synthesis through the use of a chiral metal catalyst, so-called catalytic asymmetric synthesis, which is one of the most promising methods for obtaining optically active compounds, since a small amount of chiral material can produce a large amount of chiral product [4]. 

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