Conformational enantiomers

A homodimer of a tetra-urea calix[4]arene consisting of identical phenolic units A is composed of two enantiomers with C4-symmetry, which results in overall S8-symmetry. Consequently, a heterodimer with a second calixarene consisting of four units B must be chiral, but this chirality is due only to the directionality of the hydrogen-bonded belt or (in other words) to the orientation of the carbonyl groups [42,43]. Rotation around the (four) aryl-NH bonds leads to the opposite enantiomer (conformational chirality). 

Butane exists as three conformational isomers, one anti and two gauche (Sec. 3.5). The gauche conformers, II and III, are mirror images of each other, and hence are (conformational) enantiomers. Conformers I and II (or I and III) are not mirror images of each other, and hence are (conformational) diastereomers. 

Bystricky S, Malovlikova A, Sticzay T (1991) Interaction of acidic polysaccharides with polylysine enantiomers. Conformation probe in solution. Carbohyd Pol 15 299-308... 

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. 

The value of embodies the conformation-independent 3D arrangement of the atoms of the ligands of a chirality center in distance space and thus cannot distinguish between enantiomers. This distinction is introduced by the descriptor S , , . 

The number of discrete values of/cocc(i ) determines the resolution of the chirality code. Again, is a smoothing factor. An example with the conformation-dependent chirality codes for the enantiomers of 4 in two different conformations is shown in Eigurc 8-1 f. 

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. 

Structures A and A are nonsuperimposable mirror images of each other Thus although as 1 2 dichloro cyclohexane is chiral it is optically inactive when chair-chair interconversion occurs Such interconver Sion IS rapid at room temperature and converts opti cally active A to a racemic mixture of A and A Because A and A are enantiomers interconvertible by a conformational change they are sometimes re ferred to as conformational enantiomers... 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Annelation can introduce large conformational barriers, to the extent of making possible the resolution into enantiomers of a tribenzoxepine (71CB2923). Chapters 5.16, 5.17, 5.18 and 5.19 contain much more information on inversion barriers, bond lengths and bond angles. 

Incorporation of stereogenic centers into cyclic structures produces special stereochemical circumstances. Except in the case of cyclopropane, the lowest-eneigy conformation of the tings is not planar. Most cyclohexane derivatives adopt a chair conformation. For example, the two conformers of cis-l,2-dimethylcyclohexane are both chiral. However, the two conformers are enantiomeric so the conformational change leads to racemization. Because the barrier to this conformational change is low (lOkcal/mol), the two enantiomers arc rapidly interconverted. 

FIGURE 7.10 Stereoisomeric 2,3-butanediols shown in their eclipsed conformations for convenience. Stereoisomers (a) and (b) are enantiomers of each other. Structure (c) is a diastereo-mer of (a) and (b), and is achiral. It is called meso-2,3-butanediol. 

Consider the stereochemical relationships between these flexible stereoisomers. A flexible molecule is chiral only if each of its conformers is chiral and if no two conformers are mirror images. Which, if any, of the stereoisomers are chiral Rexible chiral molecules are enantiomers only if each of their conformers are mirror-images. Which, if any, of the stereoisomers are enantiomers and which are diastereomers ... 

Now, consider the physical properties of these stereoisomers. Enantiomers should have many of the same physical properties, such as energy and dipole moment, but diastereomers should not. Obtain the energy of each conformer and use equation (1) to calculate the composition of a large sample of each stereoisomer at 298 K. Then, obtain the dipole moment of each conformer and use equatiori (2) to calculate the dipole moment of a large sample of each stereoisomer at 298 K. Do enantiomers have the same dipole moment Do diastereomers have different dipole moments ... 

Do you think it would be possible to resolve DCBP into different enantiomers at room temperature Answer this question by calculating the effective energy barrier, AE, for internal rotation (choose the lowest possible barrier), and then calculating the half-life of the favored conformers at 298 K (use equation 1). 

One interesting phenomenon was the effect of the boron substituent on enantioselectivity. The stereochemistry of the reaction of a-substituted a,/ -unsatu-rated aldehydes was completely independent of the steric features of the boron substituents, probably because of a preference for the s-trans conformation in the transition state in all cases. On the other hand, the stereochemistry of the reaction of cyclopentadiene with a-unsubstituted a,/ -unsaturated aldehydes was dramatically reversed on altering the structure of the boron substituents, because the stable conformation changed from s-cis to s-trans, resulting in production of the opposite enantiomer. It should be noted that selective cycloadditions of a-unsubsti-tuted a,/ -unsaturated aldehydes are rarer than those of a-substituted a,/ -unsatu-... 

Fig. 8-1. Schematic representations of the interaction of the (R)NapEtNH enantiomer guest with a chiral pyridine-18-crown-6 host (S,S)-1 and possible conformations of the (R)NapEt com-...

Temperature can also be used to optimize enantioselectivity in SFC. The selectivity of most CSPs increases as temperature decreases. For this reason, most chiral separations in SFC are performed at ambient or subambient temperatures [50, 74]. Subambient temperatures are particularly useful for compounds having low conformational stability [75]. Stringham and Blackwell explored the concept of entropically driven separations [76]. As temperature increased, enantioselectivity decreased until the enantiomers co-eluted at the isoelution temperature. Further increases in temperature resulted in reversal of elution order of the enantiomers. The temperature limitations of the CSP should be considered before working at elevated temperatures. 

In the case of 1,2-dibenzoylbenzene systems 3, however, it is possible to obtain the 1,4-diazocine derivatives 4 on reaction with benzene-1,2-diamines.13 - 18 The eight-membered ring exists in a tub conformation, which exhibits such a high inversion barrier that in the case of unsym-metrically substituted systems it is possible to isolate the corresponding enantiomers. 

The cyclic dimer, tetramer, and hexamer can be crystallized in acetonitrile, and also in chloroform (the former two oligomers). X-ray analysis of the crystals of the cyclic dimer47 disclosed that it consisted of a pair of different enantiomers of 53 and that all of the four substituents attached to the two tetrahydropyran rings occupied the axial position as illustrated in Fig. 54s). Such a conformation is in... 

The conformational symbols for enantiomers are different. It is therefore important to state in the context whether the d or the L form is under consideration. Enantiomers have the same reference plane (see 2-Caib-7.3), and it should be noted that the mirror image of a-D-glucose-4Ci is a-L-glucose-C4. 

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