Chirality, conformational nomenclature

Inositol is a deceptively simple molecule. On closer study, a number of sophisticated stereochemical, prochiral, chiral, and conformational issues associated with inositols and their derivatives become evident. Inositols, in particular myo-inositol, play a central role in cellular metabolism. An array of complicated molecules that incorporate the inositol moiety are found in nature. Structural heterogeneity of inositol derivatives is compounded by the presence of stereo- and regioisomers of the inositol unit. Because of the large number of isomeric inositols and their derivatives present in nature, a detailed understanding of the structural, stereochemical, and nomenclature issues involving inositol and its derivatives is essential to investigate biological aspects. A discussion of the stereochemical, conformational, prochiral, chiral, and nomenclature issues associated with inositols and the structural variety of insoitol derivatives is presented in this chapter. 

The X hgands in (80), (81) can be replaced by another chelate ring to give, for example, [M(en)3] +. Now, four conformers can be constructed for each absolute configuration A(82), or A(83) viz, XXX, XX8, X88, and 888 with A(XXX) energetically equivalent to A 888). This classification is usefid when separate enantiomers are available, but with the racemate, a chirality invariant nomenclature can be... 

Alternatively, a chirality invariant nomenclature can be used, in which the two possible conformations of an individual chelate ring in M(en)3 are named lei and ob, respectively, where the central C—C bond of the ring is (approximately) paral/e/ and oWique with respect to the C3 or pseudo-Cs symmetry axis in M(en)5" (13). Thus the four conformers are symbolized as /e/3, leliob, fe/062 and oZ 3, with lelj being equivalent to A(AAA) [or A(55 )]. 

Macropolycyclic ligands, 2,942 classification, 2,917 metal complexes binding sites, 2, 922 cavity size, 2,924 chirality, 2, 924 conformation, 2,923 dimensionality, 2, 924 electronic effects, 2, 922 shaping groups, 2,923 structural effects, 2,922 molecular cation complexes, 2,947 molecular neutral complexes, 2,952 multidentate, 2,915-953 nomenclature, 2,920 Macro tetrolide actins metal complexes, 2,973 Macrotricycles anionic complexes, 2,951 cylindrical... 

There is another point of nomenclature that must be discussed, namely where a chiral center is involved. Taking the simple case of 2-butanol, CH3CH(OH)CH2CH3, we can explain the point as follows (Scheme 1). Two configurations are possible at the chiral center. In both the R and the S series, three conformations are possible. The +sc form in the R series and the -sc form in the S series are enantiomers and their free energies must be the same under achiral conditions. However, the - sc form in the R and that in the S series differ in free energies. Therefore, it is not sufficient to call a conformation -sc if a chiral center is involved. In this case we may have to call such conformations - sc(R) and — sc(S) to distinguish them. 

One of the most extensively studied systems is that of [Co(dien)2]3+ (Table 7.1). The mer- isomer is chiral (C2) because of the two possible orientations of the proton at the secondary nitrogen atomst38,39], the unsym-fac-vsoiasi is also chiral (C2) while the sym-fac-isomer is achiral (Q). For the five-membered chelate rings all possible combinations of S and X conformations (see Fig. 6.5 for the SIX nomenclature) have to be considered, leading to a total of 40 isomers and conformers (some conformers are calculated to be unstable and may therefore be neglected144,451). The calculated distribution is based on partition functions (Eqs. 7.1, 7.2) ... 

The first three chapters constitute a review of bonding and an introduction to organic compounds. Functional groups are introduced. Resonance is covered extensively, and numerous examples are provided. Acid-base chemistry is discussed in Chapter 4, and this reaction is used to introduce many of the general features of reactions, including the effect of structure on reactivity. Nomenclature of all of the functional groups is covered in Chapters 5 and 12. In this edition, stereochemistry is covered in two chapters to break up the material Chapter 6 discusses cis trans isomers and conformations, and Chapter 7 addresses chiral molecules. 

We now consider the chair conformations of cyclohexanes that carry two substituents and examine their stereochemistry and nomenclature. Where appropriate, chirality is considered. We deal firstly with cases in which both substituents can be axial, and then those in which only one substituent can be axial at any one time. Attention is focused principally on chair conformations,... 

If two substituents are not identical, the same principles of cis/trans nomenclature still apply. However, the degeneracy is removed in the case of cis-1,3- and cw-l,2-disubstituted compounds. For example, cis-3-fluorocyclohexanecarboxylic acid (27), shown in the more populated chair conformation, is now chiral, unlike the meso 15/16. 

Conformation In a molecule of a given constitution and configuration, the spatial array of atoms affording distinction between stereoisomers that can be interconverted by rotation around single bonds. The chirality sense of conformations may be specified using the P, M nomenclature. 

A description of the molecular stereochemistry is also included in both the structural formula and nomenclature. Each ring junction can exist in either a cis or trans conformation, yielding six centers of asymmetry or chirality (C-5, 8, 9, 10, 13, 14). Hence, 64 stereoisomers are possible for the ring system alone. With the C-17 side-chain forming a seventh site of asymmetry, the theoretical number of stereoisomers increases to 128. However, in practice, the isomeric possibilities are restricted by the overall conformational limitations of the ring system. 

Often symmetry operations cannot be used in a simple way to classify chiral forms because, e.g., the molecule consists of a number of conformations. Therefore, independent of the symmetry considerations, a chemical approach to describe chiral molecules has been introduced by the use of structural elements such as chiral centers, chiral axis, and chiral planes. Examples for a chiral center are the asymmetric carbon atom, i.e., a carbon atom with four different substituents or the asymmetric nitrogen atom where a free electron pair can be one of the four different substituents. A chiral axis exists with a biphenyl (Figure 3.2) and chiral planes are found with cyclo-phane structures [17]. Chiral elements were introduced originally to classify the absolute configuration of molecules within the R, S nomenclature [16]. In cases where the molecules are chiral as a whole, so-called inherent dissymmetric molecules, special names have often been introduced atropiso-mers, i.e., molecules with hindered rotation about a helical molecules [18], calixarenes, cyclophanes [17], dendrimers [19], and others [20]. 

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