Chiral containers

However, the particular synthetic requirements in the preparation of conjugated polymers have thus far severely limited the number of similarly hierarchically structured examples. Pu et al. reported different types of conjugated polymers with fixed main-chain chirality containing binaphthyl units in their backbone which exhibited, for example, nonlinear optical activity or were used as enantioselective fluorescent sensors [42—46]. Some chirally substituted poly(thiophene)s were observed to form helical superstructures in solution [47-51], Okamoto and coworkers reported excess helicity in nonchiral, functional poly(phenyl acetylenejs upon supramolecular interactions with chiral additives, and they were able to induce a switch between unordered forms as well as helical forms with opposite helical senses [37, 52, 53]. 

The two examples presented exemplify the utility of this reaction. One can access either enantiomer of the product through the proper choice of chirality contained in the CBS reagent. This reagent possesses great scope in that simple, as well as complex, substrates can be reduced with high efficiency, chemical and optical yields. Additionally, these examples illustrate the relatively simplistic experimental conditions required to conduct these reduction reactions. 

Circular dicliroism has been a useful servant to tire biophysical chemist since it allows tire non-invasive detennination of secondary stmcture (a-helices and P-sheets) in dissolved biopolymers. Due to tire dissymmetry of tliese stmctures (containing chiral centres) tliey are biaxial and show circular birefringence. Circular dicliroism is tlie Kramers-Kronig transfonnation of tlie resulting optical rotatory dispersion. The spectral window useful for distinguishing between a-helices and so on lies in tlie region 200-250 nm and hence is masked by certain salts. The metliod as usually applied is only semi-quantitative, since tlie measured optical rotations also depend on tlie exact amino acid sequence. 

The chirality code of a molecule is based on atomic properties and on the 3D structure. Examples of atomic properties arc partial atomic charges and polarizabilities, which are easily accessible by fast empirical methods contained in the PETRA package. Other atomic properties, calculated by other methods, can in principle be used. It is convenient, however, if the chosen atomic property discriminates as much as possible between non-equivalent atoms. 3D molecular structures are easily generated by the GORINA software package (see Section 2.13), but other sources of 3D structures can be used as well. 

Twenty-eight chiral compounds were separated from their enantiomers by HPLC on a teicoplanin chiral stationary phase. Figure 8-12 shows some of the structures contained in the data set. This is a very complex stationary phase and modeling of the possible interactions with the analytes is impracticable. In such a situation, learning from known examples seemed more appropriate, and the chirality code looked quite appealing for representing such data. 

Therefore the 28 analytes and their enantiomers were encoded by the conformation-dependent chirality code (CDCC) and submitted to a Kohoiien neural network (Figure 8-1 3). They were divided into a test set of six compounds that were chosen to cover a variety of skeletons and were not used for the training. That left a training set containing the remaining 50 compounds. 

The target molecule above contains a chiral center. An enantioselective synthesis can therefore be developed We use this opportunity to summarize our knowledge of enantioselective reactions. They are either alkylations of carbanions or addition reactions to C = C or C = 0 double bonds ... 

This target molecule again contains a chiral center and we inspect Table 18 for help. Table 18. Some enantioselective reactions that produce difunctional products... 

The 1,6-difunctional hydroxyketone given below contains an octyl chain at the keto group and two chiral centers at C-2 and C-3 (G. Magnusson, 1977). In the first step of the antithesis of this molecule it is best to disconnect the octyl chain and to transform the chiral residue into a cyclic synthon simultaneously. Since we know that ketones can be produced from add derivatives by alkylation (see p. 45ff,), an obvious precursor would be a seven-membered lactone ring, which is opened in synthesis by octyl anion at low temperature. The lactone in turn can be transformed into cis-2,3-dimethyicyclohexanone, which is available by FGI from (2,3-cis)-2,3-dimethylcyclohexanol. The latter can be separated from the commercial ds-trans mixture, e.g. by distillation or chromatography. 

Recent syntheses of steroids apply efficient strategies in which open-chain or monocyclic educts with appropiate side-chains are stereoselectively cyclized in one step to a tri- or tetracyclic steroid precursor. These procedures mimic the biochemical synthesis scheme where acyclic, achiral squalene is first oxidized to a 2,3-epoxide containing one chiral carbon atom and then enzymatically cyclized to lanostetol with no less than seven asymmetric centres (W.S. Johnson, 1%8, 1976 E.E. van Tamden, 1968). 

Non-enzymatic cyclizations of educts containing chiral centres can lead to products with additional "asymmetric centres. The underlying effect is called "asymmetric induction . Its systematic exploration in steroid syntheses started when G. Saucy discovered in 1971 that a chiral carbon atom in a cyclic educt induces a stereoselective Torgov condensation several carbon atoms away (M. Rosenberger, 1971, 1972). 

Analogous definitions and designations apply to molecules containing a chiral centre and a prochiral tetrahedral or trigonal centre. The plane containing the chiral and prochiral centres is called a diastereo-zeroplane (Y. Izumi, 1977). 

In organic chemistry chirality most often occurs m molecules that contain a car bon that is attached to four different groups An example is bromochlorofluoromethane (BrClFCH)... 

To be optically active the sample must contain a chiral substance and one enantiomer must be present in excess of the other A subslance lhal does nol rolale fhe plane of polar ized lighl IS said lo be ophcally maclive All achiral substances are optically inactive... 

When a molecule contains two chirality centers as does 2 3 dihydroxybutanoic acid how many stereoisomers are possible ... 

Many naturally occurring compounds contain several chirality centers By an analysis similar to that described for the case of two chirality centers it can be shown that the maximum number of stereoisomers for a particular constitution is 2" where n is equal to the number of chirality centers... 

When two or more of a molecule s chirality centers are equivalently substituted meso forms are possible and the number of stereoisomers is then less than 2" Thus 2" represents the maximum number of stereoisomers for a molecule containing n chirality centers... 

Eleven chirality centers may seem like a lot but it is nowhere close to a world record It is a modest number when compared with the more than 100 chirality centers typ ical for most small proteins and the thousands of chirality centers present m nucleic acids A molecule that contains both chirality centers and double bonds has additional opportunities for stereoisomerism For example the configuration of the chirality center m 3 penten 2 ol may be either R or S and the double bond may be either E or Z There fore 3 penten 2 ol has four stereoisomers even though it has only one chirality center... 

Section 7 2 The most common kind of chiral molecule contains a carbon atom that bears four different atoms or groups Such an atom is called a chirality center Table 7 2 shows the enantiomers of 2 chlorobutane C 2 is a chi rahty center m 2 chlorobutane... 

Section 7 4 Optical activity, or the degree to which a substance rotates the plane of polarized light is a physical property used to characterize chiral sub stances Enantiomers have equal and opposite optical rotations To be optically active a substance must be chiral and one enantiomer must be present m excess of the other A racemic mixture is optically inactive and contains equal quantities of enantiomers... 

Section 7 9 A chemical reaction can convert an achiral substance to a chiral one If the product contains a single chirality center it is formed as a racemic mixture Optically active products can be formed from optically inactive... 

Achiral molecules that contain chirality centers are called meso forms Meso forms typically contain (but are not limited to) two equivalently substituted chirality centers They are optically inactive... 

Section 7 15 Certain polymers such as polypropylene contain chirality centers and the relative configurations of these centers affect the physical properties of... 

The enzyme is a single enantiomer of a chiral molecule and binds the coenzyme and substrate m such a way that hydride is transferred exclusively to the face of the carbonyl group that leads to (5) (+) lactic acid Reduction of pyruvic acid m the absence of an enzyme however say with sodium borohydride also gives lactic acid but as a racemic mixture containing equal quantities of the R and S enantiomers... 

Glyceraldehyde can be considered to be the simplest chiral carbohydrate It is an aldotriose and because it contains one chirality center exists in two stereoisomeric forms the D and l enantiomers Moving up the scale m complexity next come the aldotetroses Examining their structures illustrates the application of the Fischer system to compounds that contain more than one chirality center... 

Oligomer (Section 14 15) A molecule composed of too few monomer units for it to be classified as a polymer but more than in a dimer trimer tetramer etc Oligonucleotide (Section 28 6) A polynucleotide containing a relatively small number of bases Oligosaccharide (Section 25 1) A carbohydrate that gives three to ten monosacchandes on hydrolysis Optical activity (Section 7 4) Ability of a substance to rotate the plane of polanzed light To be optically active a sub stance must be chiral and one enantiomer must be present in excess of the other... 

A few GLC stationary phases rely on chemical selectivity. The most notable are stationary phases containing chiral functional groups, which can be used for separating enantiomers. ... 

In organic chemistry there are many important molecules that contain two or more groups each of which, in isolation, would be chiral. A simple example is that of 2,3-difluorobutane, shown in Figure 4.9. The molecule can be regarded as a substituted ethane and we assume that, as in ethane itself, the stable sttucture is one in which one CFIFCFI3 group is staggered relative to the other. 

Chiral separations are concerned with separating molecules that can exist as nonsupetimposable mirror images. Examples of these types of molecules, called enantiomers or optical isomers are illustrated in Figure 1. Although chirahty is often associated with compounds containing a tetrahedral carbon with four different substituents, other atoms, such as phosphoms or sulfur, may also be chiral. In addition, molecules containing a center of asymmetry, such as hexahehcene, tetrasubstituted adamantanes, and substituted aHenes or molecules with hindered rotation, such as some 2,2 disubstituted binaphthyls, may also be chiral. Compounds exhibiting a center of asymmetry are called atropisomers. An extensive review of stereochemistry may be found under Pharmaceuticals, Chiral. 

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