Searching chiral centres

A major trend in organic synthesis, however, is the move towards complex systems. It may happen that one needs to combine a steroid and a sugar molecule, a porphyrin and a carotenoid, a penicillin and a peptide. Also the specialists in a field have developed reactions and concepts that may, with or without modifications, be applied in other fields. If one needs to protect an amino group in a steroid, it is advisable not only to search the steroid literature but also to look into publications on peptide synthesis. In the synthesis of corrin chromophores with chiral centres, special knowledge of steroid, porphyrin, and alkaloid chemistry has been very helpful (R.B. Woodward, 1967 A. Eschenmoser, 1970). 

Although many questions are still open, peptide nucleic acids are easier to synthesize via simple reaction routes than is natural RNA. The PNAs have another important advantage they are achiral and uncharged, i.e., they contain no chiral centres in the polymeric backbone (see Sect. 9.4). Unfortunately, however, they do not fulfil all the necessary conditions for molecular information storage and transfer. Thus, the search for other possible candidates for a pre-RNA world continues. 

Using simple rules, a structure is represented by a string of characters unique to that structure. It can also be used to specify stereochemistry at double bonds and chiral centres. SMARTS is a further extension that allows substructure searching. 

Examples of (a) are quite common and of (b) much less common. A few are shown in Table 1. It should be observed that there are numerous d-d and d-l pairs reported as melting as the same temperature, as for example the diethyl esters of d- and tartaric acid (M.P. 17 °C). Where the chiral centre is sequestered within the molecule, and has httle or no influence on the packing shape, differences of packing energy may well be too small to be measured except under the most refined conditions (see also Section 1.12). The effects of chemical contamination must in any case put in doubt the interpretation of small differences in the search for evidence of discrimination. 

Chapters T, K and Y contain many natural products with one or two chiral centres, and the user scanning the Atlas for a compound of a particular stereochemical type should search these chapters as well as Chapter A. In order to find any individual compound, the Index should be used. 

Similarly, in creating a stereochemical designation for each chiral centre, every molecule in the database must first be oriented according to the same rules, and the same method of designating the attachments must be used for every chiral centre. In addition, the program must be able to access specific atomic information for every chiral substituent, allowing for more flexible substructure searching. 

The pharmaceutical industry is constantly searching for new drugs. Their research chemists have discovered that most of these drugs contain at least one chiral centre (see page 195). Remember that a molecule containing a carbon atom bonded to four different atoms or groups of atoms can exist as two non-superimposable mirror images. 

Oin search for a discontinuous physical property of a single molecide is discomaged, or at least diverted, by the development of the concept of continuous symmetry measures [127]. Some time ago, Zabrodsky et al. advocated that it was more natural to analyse symmetry properties in terms of a continuous scale rather than in terms of yes and no . In order to justify their view they invoked examples such as symmetry distortions due to vibrations, changes in the aUowedness of electronic transitions due to deviations from an ideal symmetry and so forth. In a similar vein and around the same time Buda et aL [128] defined a degree of chirality as a continuous function that is zero if, and only if, the object is achiral Kanis et al. [129] were motivated to use continuous symmetry measures in their study of the hyperpolarisabihty of non-Unear optic materials in order to provide correlations between structure and physical or chemical properties. Their continuous symmetry metric provided a quantitative characterisation of the extent to which the inversion centre is present for a particular geometry. It then allowed the comparison of computed hyperpolarisabUities with the extent to which the inversion centre remains. 

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