Enantiomers 2” rule

Figure 2-69. The two enantiomers of lactic acid assignment of R and S configurations to the enantiomers of lactic acid after ranking the four ligands attached to the chiral center according to the Cl P rules (OH > COjH > Me > H).

The Cahn-Ingold-Prelog (CIP) rules stand as the official way to specify chirahty of molecular structures [35, 36] (see also Section 2.8), but can we measure the chirality of a chiral molecule. Can one say that one structure is more chiral than another. These questions are associated in a chemist s mind with some of the experimentally observed properties of chiral compounds. For example, the racemic mixture of one pail of specific enantiomers may be more clearly separated in a given chiral chromatographic system than the racemic mixture of another compound. Or, the difference in pharmacological properties for a particular pair of enantiomers may be greater than for another pair. Or, one chiral compound may rotate the plane of polarized light more than another. Several theoretical quantitative measures of chirality have been developed and have been reviewed elsewhere [37-40]. 

Chemical Properties. Because of its chiral center, malic acid is optically active. In 1896, when tartaric acid was first reduced to malic acid, the levorotatory enantiomer, S(—), was confirmed as having the spatial configuration (1) (5,6). The other enantiomer (2) has the R configuration. A detailed discussion of configuration assignment by the sequence rule or the R and S system is available (7). 

Diastereomers include all stereoisomers that are not related as an object and its mirror image. Consider the four structures in Fig. 2.3. These structures represent fee four stereoisomers of 2,3,4-trihydroxybutanal. The configurations of C-2 and C-3 are indicated. Each stereogenic center is designated J or 5 by application of the sequence rule. Each of the four structures is stereoisomeric wife respect to any of fee others. The 2R R and 25,35 isomers are enantiomeric, as are fee 2R, iS and 25,3J pair. The 21 ,35 isomer is diastereomeric wife fee 25,35 and 2R,3R isomers because they are stereoisomers but not enantiomers. Any given structure can have only one enantiomer. All other stereoisomers of feat molecule are diastereomeric. The relative configuration of diastereomeric molecules is fiequently specified using fee terms syn and anti. The molecules are represented as extended chains. Diastereomers wife substituents on the same side of the extended chain are syn stereoisomers, whereas those wife substituents on opposite sides are anti stereoisomers. 

Most of the molecules we take into our bodies, whethei in food or in medicine, are chiral. As a rule, differeni enantiomers of these molecules have different biologica consequences. 

Dezocine (30) represents a class of bridged aminotetralins possessing morphine-like analgesic properties. It appears to be roughly equivalent in potency and addiction potential to morphine. The molecule combines molecular features of precedent aminotetralins and benzomor-phans and its structure fits the classical Morphine Rule. The 1-enantiomer is the more active and the p-epimer (equatorial NHj) is the active diastereomer. 

As a general rule, the reaction of a chiral reactant with an achiral reactant leads to unequal amounts of diastereomeric products. If the chiral reactant is optically active because only one enantiomer is used rather than a racemic mixture, then the products are also optically active. 

Sequence rules, 180-183, 297-298 E,Z alkene isomers and, 180-183 enantiomers and. 297-300 Serine, biosynthesis of, 1177... 

The empirical rule described above for the enantiofacial differentiation in AE of primary allylic alcohols also applies to secondary allylic alcohols. The new aspect that needs to be taken into consideration in this case is the steric hindrance arising from the presence of a substituent (R4) at the carbon bearing the hydroxy group (Figure 6.3). This substituent will interfere in the process of oxygen delivery, making the oxidation of one enantiomer much faster than the reaction of the other one. The phenomenon is so acute that in practice kinetic resolution is often achieved (Figure 6.4) [27]. 

The Cahn-Ingold-Prelog system is unambiguous and easily applicable in most cases. Whether to call an enantiomer (R) or (S) does not depend on correlations, but the configuration must be known before the system can be applied, and this does depend on correlations. The Cahn-Ingold-Prelog system has also been extended to chiral compounds that do not contain chiral atoms.A series of new rules have been proposed to address the few cases where the rules can be ambiguous, as in cyclophanes and other systems. ... 

Although four is the maximum possible number of isomers when the compound has two chiral centers (chiral compounds without a chiral carbon, or with one chiral carbon and another type of chiral center, also follow the rules described here), some compounds have fewer. When the three groups on one chiral atom are the same as those on the other, one of the isomers (called a meso form) has a plane of symmetry, and hence is optically inactive, even though it has two chiral carbons. Tartaric acid is a typical case. There are only three isomers of tartaric acid a pair of enantiomers and an inactive meso form. For compounds that have two chiral atoms, meso forms are found only where the four groups on one of the chiral atoms are the same as those on the other chiral atom. 

The precision of the data is not such as to allow non-dipole interactions to be definitively ruled out, and more detailed study of this topic by careful measurement of the full angular distribution, as opposed to detection at a single angle, will be required to provide a complete probe. In the meantime a clear observation that enantiomer PECD curves have a mirror-image relationship... 

The question was whether impurities were present in the samples analysed (Bada et al., 1983). In a more recent publication, Cronin and Pizzarello (1997) reported amino acid analyses using Murchison material in which an excess of L-enantiomers was present. Contamination with terrestrial biological material can be ruled out, as the amino acids in question are not proteinogenic a-methylamino acids, which occur either extremely seldom or not at all in terrestrial life forms, were detected. GLPC/mass spectrometry (MS) analysis gave the following enantiomeric excess (ee) values ... 

UV radiation hypothetical, but so is the transport of molecules from outer space to Earth. Recent analyses of the Murchison meteorite by two scientists from the University of Arizona, Tucson (Cronin and Pizzarello, 1997 Cronin, 1998) have shown it to contain the four stereoisomeric amino acids DL-a-methylisoleucine and DL-a-methylalloisoleucine. In both cases, the L-enantiomer is present in a clear excess (7.0 and 9.1%). Similar results were obtained for two other a-methyl amino acids, isovaline and a-methylvaline. Contamination by terrestrial proteins can be ruled out, since these amino acids are either not found in nature or are present in only very small amounts. Since the carbonaceous chondrites are thought to have been formed around 4.5 billion years ago (see Sect. 3.3.2), the amino acids referred to above must have been subject to one or more asymmetric effects prior to biogenesis. 

If the molecular species of the solute present in solution is the same as those present in the crystals (as would be the case for nonelectrolytes), then to a first approximation, the solubility of each enantiomer in a conglomerate is unaffected by the presence of the other enantiomer. If the solutions are not dilute, however, the presence of one enantiomer will influence the activity coefficient of the other and thereby affect its solubility to some extent. Thus, the solubility of a racemic conglomerate is equal to twice that of the individual enantiomer. This relation is known as Meyerhoffer s double solubility rule [147]. If the solubilities are expressed as mole fractions, then the solubility curves are straight lines, parallel to sides SD and SL of the triangle in Fig. 24. 

If solvent is added to either of the solid eutectics represented by e or e in Fig. 25a or b, the undissolved solid retains this composition while the saturated solution maintains the composition E or E, respectively. Again, Gibbs phase rule [145,146] can provide further insight into these systems. If the solid enantiomers are solvated, the compositions of the equilibrium solids are displaced symmetrically along the DS or LS axes to an extent determined by the stoichiometry of the solvates. Similarly, if the racemic compound is solvated, the stoichiometry of the equilibrium solid is displaced from R along the line RS to an extent determined by the stoichiometry of the solvate. 

Three-dimensional (3-D) descriptors of molecules quantify their shape, size, and other structural characteristics which arise out of the 3-D disposition and orientation of atoms and functional groups of molecules in space. A special class of 3-D indices is quantitative descriptors of chirality. If a molecule has one or more chiral centers, the spatial disposition of atoms can produce enantiomers, many of which will have the same magnitude of calculated and experimental physicochemical properties having, at the same time, distinct bioactivity profiles. Basak and coworkers [22] have developed quantitative chirality indices to discriminate such isomers according to their structural invariants which are based on the Cahn-Ingold-Prelog (CIP) rules. 

Another cooperativity effect, dubbed majority rule has also been noted. Where opposite enantiomer chiral groups are both present in side chains, such as (S) and (l )2-methylbutyl groups, the overall helicity is determined in a non-linear manner by the ee only, as is evident in Figure 42. 

The geometrical isomers are xxii and xxiii. The cis and trans both will exist in two optically active forms along with their one racemic modification. Therefore, the optically active forms of cis and trans will all be different and we will have two pairs of enantiomers. This is also according to the rule of 2 optically active forms where n represents the number of different chiral centres. 

With isotopes it has been possible to show that all enzyme-catalyzed reactions are stereospecific. Before the availability of isotopes, there was no way of testing this generalization. Of course there are some apparent exceptions to prove the rule. Bently has listed a considerable number (2>, Table XIII, Chapter 6). The most interesting one to me seems to be luciferase, but that is an exception that isn t an exception. Thus, the enzyme luciferase acts on its substrate luciferin (2), in the presence of ATP and O2, to oxidize the luciferin to oxyluciferin (3). The reaction consists of an initial activation of the substrate by ATP to give luciferyl adenylate, after which the oxidation takes place. When the natural enantiomer (synthesized from D-cysteine) is activated and oxidized, light is emitted. The other enantiomer is also acted on by the enzyme, and is converted to the adenylate, but oxyluciferin is not formed, and there is no bioluminescence 37,38,38a)... 

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