Racemates s. Stereoisomers

Racemates s. Stereoisomers Racemization s. under Radical reactions Radical reactions... 

Conduritols and inositols are cyclic polyalcohols with significant biological activity. The presence of four stereogenic centers in the stmcture of conduritols allows the existence of 10 stereoisomers. Enzymatic methods have been reported for the resolution of racemic mixtures or the desymmetrization of meso-conduritols. For example, Mucor miehei lipase (MML) showed enantiomeric discrimination between all-(R) and all-(S) stereoisomers ofconduritol E tetraacetate (Figure 6.52). Alcoholysis resulted in the removal of the four acetyl groups ofthe all-(R) enantiomer whereas the all-(S) enantiomer was recovered [141]. 

Resuscitation from bupivacaine cardiovascular toxicity is extremely difficult. However, prompt resuscitation has been successful with standard cardiopulmonary support, including the prompt correction of acidosis by hyperventilation and administration of bicarbonate as well as epinephrine, atropine, and bretylium. Local anesthetics, especially bupivacaine, also inhibit basal and epinephrine-stimulated cAMP production. This finding places greater emphasis on aggressive epinephrine therapy during bupivacaine-induced cardiotoxicity. The (SJ-isomer, levobupivacaine, appears to have a lower propensity for cardiovascular toxicity than the racemic mixture or the (R)-isomer and has recently been approved for clinical use. Ropivacaine, another newer local anesthetic, has clinical effects similar to those of bupivacaine but may be associated with a lower potential for cardiovascular toxicity. Ropivacaine is available only as the (S)-stereoisomer, which has inherently less affinity for the cardiac sodium channel. 

Regarding production of bulk drug substances, specifications for contaminants should be established for all solvents used in the process. A comparison should be performed between the manufacturer s Certificate of Analysis and the submitted specifications, and any discrepancies should be justified. A full description for the route of synthesis should be given, as this is important for the testing and control of impurities and process solvent residues. The FDA expects that, at the time of submission, it will be determined if the drug substance exists in a multiple solid state form (racemic mixture stereoisomer) and whether this affects the dissolution and bioavailability of the drug product. 

To illustrate this strategy, we begin again with the two enantiomers of Ai-acetyl alanine, which were prepared by treating a racemic mixture of R)- and (S)-alanine with acetic anhydride (Section 28.3A). Enzymes called acylases hydrolyze amide bonds, such as those found in Ai-acetyl alanine, but only for amides of L-amino acids. Thus, when a racemic mixture of Ai-acetyl alanines is treated with an acylase, only the amide of L-alanine (the S stereoisomer) is hydrolyzed to generate L-alanine, whereas the amide of D-alanine (the R stereoisomer) is untouched. The reaction mixture now consists of one amino acid and one Ai-acetyl amino acid. Because they have different functional groups with different physical properties, they can be physically separated. 

Most albuterol sulfate preparations contain an equimolar, racemic mixture of the (R)- and (S)-stereoisomers (Page Morley 1999). (R)-albuterol has bronchodilator and bronchoprotec-tive activity. (S)-Albuterol does not activate P2 adrenoceptors and does not modify the activation of these receptors by (R)-albuterol. (S)-Albuterol is metabolized more slowly than (R)-albuterol and is retained preferentially in the airways. Until recently, (S)-albuterol was considered biologically inert however, it has been shown to intensify allergic bronchospasm and eosinophilic activation in laboratory animals and appears to have the potential to induce paradoxical reactions in some asthmatic patients. In horses, (S)-albuterol does not have bronchodilatory activity and stimulates acetylcholine release via prejunctional 2 adrenoceptor stimulation (Zhang et al 1998). Levalbuterol (homochiral (R)-albuterol) has been marketed recently and reportedly dramatically reduces the incidence of the side-effects associated with racemic albuterol in some patients. 

Although not explicitly shown, both (f )-(-)-3-methyl-2-butanol and racemic 3-methy 1-2-butanol produce spectra identical to the spectrum of the S stereoisomer. The diastereomeric effect is not limited to a solution of one pure enantiomer, free of the other. 

In these, racemic means a racemic mixture of R.R and S,S stereoisomers. 

In contrast, when ethyl acetoacetate is reduced with sodium borohydride in methanol, the reaction yields a 50-50 mixture of the (R) and (S)-stereoisomers. A racemic mixture is formed because the reaction is not being conducted in a chiral medium. 

Proceed Because it functions in both roles in this reaction, the transformation occurs rapidly. Each time displacement occurs, the stereocenter undergoes stereochemical inversion. Because the process is fast, it takes place multiple times for every substrate molecule, inverting the stereochemistry each time. Ultimately, this leads to an equilibrium (i.e., racemic) mixture of (P) and (S) stereoisomers of the starting (and ending) compound. 

Thus, the reaction will produce a racemic mixture consisting of the (R) and (S) stereoisomers of 2-methoxy-4-methylpentane. 

Recall from Section 7.13 that a stereospecific reaction is one in which each stereoisomer of a particular starting material yields a different stereoisomeric form of the reaction product. In the examples shown, the product from Diels-Alder cycloaddition of 1,3-butadiene to c/s-cinnamic acid is a stereoisomer of the product from trans-cinnamic acid. Each product, although chiral, is formed as a racemic mixture. 

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

Addition of metalated, enantiomerically pure a-sulfinyl dimethylhydrazones (e.g., 9) to racemic a-chiral aldehydes 10 proceeds with good to excellent diastereo- and enantioselectivi-ty12. Diastereomeric ratios increase with increasing steric demand of the acetaldehyde substituent R1 compared to the methyl group, and each diastereomer is obtained with high enantiomeric excess. In the aldol-lype addition to 2-phenylpropanal, one of the four possible stereoisomers is formed selectively. The relative (syn) and absolute (R.R) configuration is in accord with Cram s and related rules as well as H-NMR data of closely related compounds. 

Usually, stereocenters are drawn with dashes and wedges to show the configuration. If the dashes and wedges are not drawn, then we assume that there is a mixture of equal amounts of both configurations (which we call a racemic mixture). In fact, in the compound above, there is a second stereocenter. Can you find it Each of the two stereocenters in the compound above can be either R or S. Since there are two stereocenters, there will be four possibilities R,R and R,S and S,R and S,S. Since neither stereocenter has been drawn with dashes and wedges, we must assume that we have all four possible stereoisomers. 

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