S enantiomers

Application of the CCM to small sets (n < 6) of enzyme inhibitors revealed correlations between the inhibitory activity and the chirality measure of the inhibitors, calculated by Eq. (26) for the entire structure or for the substructure that interacts with the enzyme (pharmacophore) [41], This was done for arylammonium inhibitors of trypsin, Di-dopamine receptor inhibitors, and organophosphate inhibitors of trypsin, acetylcholine esterase, and butyrylcholine esterase. Because the CCM values are equal for opposite enantiomers, the method had to be applied separately to the two families of enantiomers (R- and S-enantiomers). 

Recently Desimoni et used the same bis(oxazoline) ligand in the magnesium(II) catalysed Diels-Alder reaction of the N-acyloxazolidinone depicted in Scheme 3.4. In dichloromethane a modest preference was observed for the formation of the S-enantiomer. Interestingly, upon addition of two equivalents of water, the R-enantiomer was obtained in excess. This remarkable observation was interpreted in terms of a change from tetrahedral to octahedral coordination upon the introduction of the strongly coordinating water molecules. 

Figure 7 7 shows why equal amounts of (R) and (5) 1 2 epoxypropane are formed m the epoxidation of propene There is no difference between the top face of the dou ble bond and the bottom face Peroxyacetic acid can transfer oxygen to either face with equal facility the rates of formation of the R and S enantiomers of the product are the same and the product is racemic... 

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance The best examples are found m biochemical processes Most bio chemical reactions are catalyzed by enzymes Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment m which chemical reaction can take place Ordinarily enzyme catalyzed reactions occur with such a high level of stereo selectivity that one enantiomer of a substance is formed exclusively even when the sub strate is achiral The enzyme fumarase for example catalyzes hydration of the double bond of fumaric acid to malic acid m apples and other fruits Only the S enantiomer of malic acid is formed m this reaction... 

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... 

Organic chemists often use enantiomencally homogeneous starting materials for the synthe SIS of complex molecules (see Chiral Drugs p 296) A novel preparation of the S enantiomer of compound B has been descnbed using a bacterial cyclohexanone monooxygenase enzyme system... 

During a resolution process, the R- and S-enantiomers compete for the free enzyme to form the noncovalent enzyme—substrate complexes ES and ER. These proceed to form transition-state intermediates [ES] and [ER] ... 

Porcine liver esterase (PLE) gives excellent enantioselectivity with both dimethyl 3-methylglutarate [19013-37-7] (lb) and malonate (2b) diester. It is apparent from Table 1 that the enzyme s selectivity strongly depends on the size of the alkyl group in the 2-position. The hydrolysis of ethyl derivative (2c) gives the S-enantiomer with 75% ee whereas the hydrolysis of heptyl derivative (2d) results in the R-monoester with 90% ee. Chymotrypsin [9004-07-3] (CT) does not discriminate glutarates that have small substituents in the 3-position well. However, when hydroxyl is replaced by the much bulkier benzyl derivative (Ic), enantioselectivity improves significantly. 

The numerical constants were obtained over the temperature range of 5°C to 45°C and a concentration range of 0 to 0.5 volume fraction of ethanol inn-hexane.The effect of temperature and solvent composition on solute retention can, again, be best displayed by the use of 3-D graphs, and curves relating both temperature and solvent composition to the retention volume of the (S) enantiomer of 4-benzyl-2-oxazolidinone are shown in Figure 23. Figure 23 shows that the volume fraction of ethanol in the solvent mixture has the major impact on solute retention. 

FIGURE 7.6 Ball-and-spoke models (/eft), wedge-and-dash drawings (center), and Fischer projections (right) of the R and S enantiomers of bromochlorofluoromethane. 

Enantiomers must have equal and opposite specific rotations. Diastereomers can have different rotations, with respect to both sign and magnitude. Thus, as Eigure 7.8 shows, the (2/ ,3/ ) and (2.S,3.S) enantiomers (I and II) have specific rotations that aie equal in magnitude but opposite in sign. The (2/, 3S) and (2S,3/i) enantiomers (III and IV) likewise have specific rotations that aie equal to each other but opposite in sign. The magnitudes of rotation of I and II aie different, however, from those of their diastereomers III and IV. 

Most of the biochemical reactions that take place in the body, as well as many organic reactions in the laboratory, yield products with chirality centers. Fo example, acid-catalyzed addition of H2O to 1-butene in the laboratory yield 2-butanol, a chiral alcohol. What is the stereochemistry of this chiral product If a single enantiomer is formed, is it R or 5 If a mixture of enantiomers i formed, how much of each In fact, the 2-butanol produced is a racemic mix ture of R and S enantiomers. Let s see why. 

The S enantiomer of ibuprofen soothes the aches and pains of athletic injuries much more effectively than the R enantiomer. 

The synthesis of an a-amino acid from an achiral precursor by any of the methods described in the previous section yields a racemic mixture, with equal amounts of S and R enantiomers. To use an amino acid in the laboratory synthesis of a naturally occurring protein, however, the pure S enantiomer must be obtained. 

---