In chiral structures

The culmination of the studies on asymmetric photodimerization reactions in the solid state was the successful elaboration of chemical systems that are achiral but crystallize in chiral structures, and that yield, on irradiation, dimers, trimers, and higher oligomers in quantitative enantiomeric yield (175,258). 

Systematic studies of topochemical reactions of organic solids have led to the possibility of asymmetric synthesis via reactions in chiral crystals. (A chiral crystal is one whose symmetry elements do not interrelate enantiomers.) (Green et al, 1979 Addadi et al, 1980). This essentially involves two steps (i) synthesis of achiral molecules that crystallize in chiral structures with suitable packing and orientation of reactive groups and (ii) performing a topochemical reaction such that chirality of crystals is transferred to products. The first step is essentially a part of the more general problem of crystal engineering. An example of such a system where almost quantitative asymmetric induction is achieved is the family of unsymmetrically substituted dienes ... 

Finally, it should be noted that other spectral analyses such as Raman, nuclear magnetic resonance, and fluorescence spectroscopies, which are correlated to more local chemical entities or individual atoms in the molecular systems, complement the CD data. Although other spectral approaches may provide more effective tools for analyzing a local structure or individual atoms in the molecular systems than the CD does, the CD approach is indispensable for the estimation of change or population in chiral structures on the average. 

The crystallization of achiral molecules in chiral space groups, while rare and unpredictable, is well documented. Molecules with a C2 symmetry axis tend to crystallize in chiral structures, according to Jacques and coworkers, but despite impressive work on crystal engineering, predictions of a correlation between crystal symmetry and molecular structures are still hard to make [6]. 

We have thus far discussed in this section some of the factors associated with crystallization in chiral structures, and pointed out that the molecules in such structures must adopt conformations which are to some extent chiral, whether or not they do so in disperse phases. Because of the chirality of both the molecule and of its environment, if the molecule takes part in a topochemically controlled solid-state reaction it is conceivable that chiral non-racemic products would be produced. In fact two successful asymmetric syntheses of this sort have been carried out in this laboratory. 

Two such systems are of particular interest from the point of view of asymmetric polymers, and both of them would be expected to lead to quantitative optical yields if the contacts shown below are the only ones leading to reaction. Both involve monomers with two, non-identical double bonds, in chiral structures. In the first [9], transoid diene molecules are translationally related, with the non-identical double bonds suitable spaced and oriented to give topochemical photocyclopolymerization. 

The solution to our problem lies in the choice of an unsymmetrically substituted diene which will crystallize in a chiral structure with the required packing arrangement [29]. To guide our choice we utilized a number of empirical facts. Thus we avoided the use of carboxylic acids and amides, since these generally lead to centrosymmetric structures [37, 38]. Esters, nitriles, and ketones, on the other hand, frequently crystallize in chiral structures. 

Finally, a word about the use of chiral handles. Until there is a much deeper understanding of the factors which induce achiral molecules to crystallize in chiral structures, the trial-and-error method of attempting to achieve such crystallizations is likely to be very ineffective. The use of chiral handles completely transforms this picture and makes it possible to utilize a wide variety of monomer types and be relatively confident of achieving chiral crystal structures. 

If compounds have the same topology (constitution) but different topography (geometry), they are called stereoisomers. The configuration expresses the different positions of atoms around stereocenters, stereoaxes, and stereoplanes in 3D space, e.g., chiral structures (enantiomers, diastereomers, atropisomers, helicenes, etc.), or cisftrans (Z/E) configuration. If it is possible to interconvert stereoisomers by a rotation around a C-C single bond, they are called conformers. 

Chiral carbon atoms are common, but they are not the only possible centers of chirality. Other possible chiral tetravalent atoms are Si, Ge, Sn, N, S, and P, while potential trivalent chiral atoms, in which non-bonding electrons occupy the position of the fourth ligand, are N, P, As, Sb, S, Se, and Te. Furthermore, a center of chirality does not even have to be an atom, as shown in the structure represented in Figure 2-70b, where the center of chirality is at the center of the achiral skeleton of adamantane. 

The neighborhoods of the atoms directly bonded to tbe chiral center must be defined. The neighborhood of an atom A. dircetly bonded to the ehiral eenter, is dc-fned as the set of atoms whose distance (in number of bonds) to A is less than their distance to any of the other three atoms bonded to the chiral center (Figure 8-9. In cyclic structures different neighborhoods can overlap. 

FIGURE 7 12 Chohc acid Its 11 chirality centers are those carbons at which stereochemistry is indicated in the structural drawing at the left The molecular model at the right more dearly shows the overall shape of the molecule... 

Liquid Crystalline Structures. In certain ceUular organeUes, deoxyribonucleic acid (DNA) occurs in a concentrated form. Striking similarities between the optical properties derived from the underlying supramolecular organization of the concentrated DNA phases and those observed in chiral nematic textures have been described (36). Concentrated aqueous solutions of nucleic acids exhibit a chiral nematic texture in vitro (29,37). 

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. ... 

Chiral Controller. (Synonymous with Chiral Auxiliary). A chiral structural unit which when attached to a substrate enhances stereoselectivity in the formation of new stereocenter(s). 

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

Whereas the utility of these methods has been amply documented, they are limited in the structures they can provide because of their dependence on the diazoacetate functionality and its unique chemical properties. Transfer of a simple, unsubstituted methylene would allow access to a more general subset of chiral cyclopropanes. However, attempts to utilize simple diazo compounds, such as diazomethane, have never approached the high selectivities observed with the related diazoacetates (Scheme 3.2) [4]. Traditional strategies involving rhodium [3a,c], copper [ 3b, 5] and palladium have yet to provide a solution to this synthetic problem. The most promising results to date involve the use of zinc carbenoids albeit with selectivities less than those obtained using the diazoacetates. 

The need for an overall and combined chemical structure and data search system became clear to us some time ago, and resulted in the decision to build CHIRBASE, a molecular-oriented factual database. The concept utilized in this database approach is related to the importance of molecular interactions in chiral recognition mechanisms. Solely a chemical information system permits the recognition of the molecular key fingerprints given by the new compound among thousands of fingerprints of known compounds available in a database. 

In this chapter, we will discuss the present status of CHIRBASE and describe the various ways in which two (2D) or three-dimensional (3D) chemical structure queries can be built and submitted to the searching system. In particular, the ability of this information system to locate and display neighboring compounds in which specified molecular fragments or partial structures are attached is one of the most important features because this is precisely the type of query that chemists are inclined to express and interpret the answers. Another aspect of the project has been concerned with the interdisciplinary use of CHIRBASE. We have attempted to produce a series of interactive tools that are designed to help the specialists or novices from different fields who have no particular expertise in chiral chromatography or in searching a chemical database. 

The ending caine stems from cocaine, the first clinically employed local anaesthetic. Procaine and tetracaine are ester-linked substances, the others are amides. Amide bonded local anaesthetics usually contain two i s in their name, ester-bonded only one. In the structure drawings, the lipophilic portion of the molecule is depicted at the left, the amine at the right. The asterisk marks the chiral centre of the stereoisomeric drugs. Lipid solubility is given as the logarithm of the water octanol partition coefficient, log(P). 

In addition to the sensitivity to ring structure, slight alterations of the hydrocarbon chain may lead to dramatic differences in electro-optic performance in chiral compounds [43]. For example, in some electroclinic Sm-A materials it has been reported that if the chain is shortened or if a double bond is localised at the end of the hydrocarbon chain, the tilt angle, electroclinic coefficient, and switching time are significantly suppressed [43]. 

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