Stereoisomers, racemic mixtures

Epoxidation of alkenes is a stereospecific syn addition Which stereoisomer of 2 butene reacts with peroxyacetic acid to give meso 2 3 epoxybu tane Which one gives a racemic mixture of (2/ 3/ ) and (25 35) 2 3 epoxybutane ... 

The separation of a racemic mixture into its enantiomeric components is termed resolution The first resolution that of tartaric acid was carried out by Louis Pasteur m 1848 Tartaric acid IS a byproduct of wine making and is almost always found as its dextrorotatory 2R 3R stereoisomer shown here m a perspective drawing and m a Fischer projection... 

DUactide (5) exists as three stereoisomers, depending on the configurations of the lactic acid monomer used. The enantiomeric forms whereia the methyl groups are cis are formed from two identical lactic acid molecules, D- or L-, whereas the dilactide formed from a racemic mixture of lactic acid is the opticaUy iaactive meso form, with methyl groups trans. The physical properties of the enantiomeric dilactide differ from those of the meso form (6), as do the properties of the polymers and copolymers produced from the respective dilactide (23,24). 

When additional substituents ate bonded to other ahcycHc carbons, geometric isomers result. Table 2 fists primary (1°), secondary (2°), and tertiary (3°) amine derivatives of cyclohexane and includes CAS Registry Numbers for cis and trans isomers of the 2-, 3-, and 4-methylcyclohexylamines in addition to identification of the isomer mixtures usually sold commercially. For the 1,2- and 1,3-isomers, the racemic mixture of optical isomers is specified ultimate identification by CAS Registry Number is fisted for the (+) and (—) enantiomers of /n t-2-methylcyclohexylamine. The 1,4-isomer has a plane of symmetry and hence no chiral centers and no stereoisomers. The methylcyclohexylamine geometric isomers have different physical properties and are interconvertible by dehydrogenation—hydrogenation through the imine. 

The structure of a natural product is shown without any specification of stereochem-istiy. It is a pure substance which gives no indication of being a mixture of stereoisomers and has zero optical rotation. It is not a racemic mixture because it does not yield separate peaks on a chiral HPLC column. When the material is completely hydrolyzed, it gives a racemic sample of the product shown. Deduce the complete stereochemical structure of the natural product fiom this information. 

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. 

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]. 

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. 

Percentage cross-reactivity is defined as the ratio of the IC50 of the testing substance (ractopamine stereoisomer or metabohte) and the IC50 of the ractopamine racemic mixture, expressed as a percentage. 

Lactide (LA), the cyclic diester of lactic acid, has two stereogenic centers and hence exists as three stereoisomers L-lactide (S,S), D-lactide (R,R), and meso-lactide (R,S). In addition, rac-lactide, a commercially available racemic mixture of the (R,R) and (S,S) forms, is also frequently studied. PLA may exhibit several stereoregular architectures (in addition to the non-stereoregular atactic form), namely isotactic, syndiotactic, and heterotactic (Scheme 15). The purely isotactic form may be readily prepared from the ROP of L-LA (or D-LA), assuming that epimerization does not occur during ring opening. The physical properties, and hence medical uses, of the different stereoisomers of PLA and their copolymers vary widely and the reader is directed to several recent reviews for more information.736 740-743... 

CAS 64285-06-9 92142-32-0 (Stereoisomer) 85514-42-7 (Racemic mixture) 92844-80-9 (p-Toluenesulfonate salt) 92216-03-0 (Hydrochloride salt) 70470-07-4 (Hydrochloride salt) 122564-82-3 (Butenedioate salt)... 

Weevils do not seem to be very sensitive to the presence of non-natural stereoisomers of their pheromones, since racemic mixtures proved to be active in the field. This greatly facilitates their use in large-scale integrated pest management. Some species also contain ketones, corresponding to the pheromone alcohols however, they do not show behavioural activity. 

The two forms of mirror images are called enantiomers, or stereoisomers. All amino acids in proteins are left-handed, and all sugars in DNA and RNA are right-handed. Drug molecules with chiral centers when synthesized without special separation steps in the reaction process result in 50/50 mixtures of both the left- and right-handed forms. The mixture is often referred to as a racemic mixture. 

Table 3.4. Possible advantages of the single stereoisomer over the racemic mixture...

Many of these substituted lactones possess at least one chiral center and are thus present as a mixture of stereoisomers. The simplest case is based on the polymerization of lactones with one chiral center, which is thus a mixture of two R and S enantiomers. These stereochemical aspects have been completely overlooked in many works the polymerization is carried out on a racemic mixture and no stereo selectivity is reported or even discussed. It is worth pointing out that several metal-based catalysts were successfully designed for the stereoselective polymerization of... 

A C2-symmetric ansa metallocene is a racemic mixture of an enantiomeric pair—an example is rac-(dimethylsilyl)bis(l-indenyl)zirconium dichloride (XXXIV), abbreviated as rac-(CH3)2SiInd2ZrCl2. The enantiomers are designated as (R, R) and (S, S) to describe the two coordination sites in each enantiomer. Actually, the synthesis of a C2 ansa metallocene usually produces a mixture of the racemic pair plus the meso compound (R, S). The meso compound, which is a diastereomer of the racemic pair, can be separated from the racemic mixture by physical techniques such as recrystallization. The meso stereoisomer possesses Cs symmetry, and its stereoselectivity is very different from that of the enantiomeric pair (Sec. 8-5a-3). 

Sharpless Asymmetric Epoxidation This is a method of converting allylic alcohols to chiral epoxy alcohols with very high enantioselectivity (i.e., with preference for one enantiomer rather than formation of racemic mixture). It involves treating the allylic alcohol with tert-butyl hydroperoxide, titanium(IV) tetra isopropoxide [Ti(0—/Pr)4] and a specific stereoisomer of tartaric ester. For example,... 

Definitions It is important to define precisely the stereochemical terms that will be employed in this discussion. The term racemization has often been used loosely by chemists to describe any situation in which a mixture of enantiomers or diastereomers is produced as a result of an amide-bond-forming reaction, without regard to the ratio of stereoisomers formed. For the purposes of this discussion though, the term racemization will be used to describe the situation leading toward the formation of an exact 1 1 mixture of stereoisomers. Racemization, therefore, is a process that occurs to a collection of molecules, and can happen to a single residue or to one residue in a peptide sequence (Scheme 1). This is a macroscopic event, as the result is detected subsequent to the amide bond formation. 

Ibuprofen is a popular analgesic and anti-inflammatory drug. There are two stereoisomeric forms of ibuprofen. This drug can exist as (S)- and (/ )-stereoisomers (enantiomers). Only the (5)-form is active. The (/ )-form is completely inactive, although it is slowly converted in the body to the active (5)-form. The drug marketed under the trade names, commercially known as Advil , Anadin , Arthrofen , Brufen , Nurofen , Nuprin , Motrin etc., is a racemic mixture of (/ )- and (5)-ibuprofen. 

Dobutamine is a directly acting synthetic catecholamine with predominant effects at pi receptors. It has weak 32 and a effects. It is a racemic mixture and both stereoisomers are p-adrenoceptor agonists. The (+) isomer is approximately ten times more potent as a p-receptor agonist than the (-) isomer, which is mainly responsible for the o-adrenoceptor activity. Unlike dopamine, dobutamine does not act by releasing noradrenaline or via dopaminergic receptors. 

Resuscitation from bupivacaine cardiovascular toxicity is extremely difficult even for experienced clinicians. Recent studies suggest that propofol can be useful in resuscitating patients acutely exposed to toxic levels of bupivacaine. The (S)-isomer, levobupivacaine, appears to have a lower propensity for cardiovascular toxicity than the racemic mixture or the (7 >isomer and has been approved for clinical use. The clinical effects of ropivacaine are similar to those of bupivacaine, but ropivacaine is allegedly associated with a lower potential for cardiovascular toxicity. Ropivacaine is available only as the ( SJ-stereoisomer, which has inherently less affinity for the cardiac sodium channel. However, both cardiac toxicity and CNS toxicity have been reported when large doses of ropivacaine were used for peripheral nerve blocks. 

Stereoisomer Assays. There are many drugs that are administered as racemic mixtures. They may undergo stereoselective metabolism and/or elimination, and one isomer may be more active than the other. Therefore, there is the need to develop and validate bioanalytical assays for stereoselective determination in bioavailability/bioequivalence studies. All methods used for measurement of stereoisomer should be validated (with emphasis on stereospecificity). For bioequivalence studies of an existing racemic product, a stereospecific assay is not required if the rate and extent of profiles are superimposable (within the usual statistical boundaries) [3,23]. 

It is remarkable that virtually all amino acid residues in proteins are L stereoisomers. When chiral compounds are formed by ordinary chemical reactions, the result is a racemic mixture of d and l isomers, which are difficult for a chemist to distinguish and separate. But to a living system, D and L isomers are as different as the right hand and the left. The formation of stable, repeating substructures in proteins (Chapter 4) generally requires that their constituent amino acids be of one stereochemical series. Cells are able to specifically synthesize the l isomers of amino acids because the active sites of enzymes are asymmetric, causing the reactions they catalyze to be stereospecific. 

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