Diastereomers chiral molecules

The introduction of a THP ether onto a chiral molecule results in the formation of diastereomers because of the additional stereogenic center present in the tetrahy-dropyran ring (which can make the interpretation of NMR spectra somewhat troublesome at times). Even so, this is one of the most widely used protective groups employed in chemical synthesis because of its low cost, the ease of its installation, its general stability to most nonacidic reagents, and the ease with which it can be removed. 

Consider the stereochemical relationships between these flexible stereoisomers. A flexible molecule is chiral only if each of its conformers is chiral and if no two conformers are mirror images. Which, if any, of the stereoisomers are chiral Rexible chiral molecules are enantiomers only if each of their conformers are mirror-images. Which, if any, of the stereoisomers are enantiomers and which are diastereomers ... 

B The fourth possibility arises in chiral molecules, such as (R)-2-butanol. The two — CH2- hydrogens at C3 are neither homotopic nor enantiotopic. Since replacement of a hydrogen at C3 would form a second chirality center, different diastereomers (Section 9.6) would result depending on whether the pro-R or pro-S hydrogen were replaced. Such hydrogens, whose replacement by X leads to different diastereomers, are said to be diastereotopic. Diastereotopic hydrogens are neither chemically nor electronically equivalent. They are completely different and would likely show different NMR absorptions. 

A closely related method does not require conversion of enantiomers to diastereomers but relies on the fact that (in principle, at least) enantiomers have different NMR spectra in a chiral solvent, or when mixed with a chiral molecule (in which case transient diastereomeric species may form). In such cases, the peaks may be separated enough to permit the proportions of enantiomers to be determined from their intensities. Another variation, which gives better results in many cases, is to use an achiral solvent but with the addition of a chiral lanthanide shift reagent such as tris[3-trifiuoroacetyl-Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for examples, alcohols, carbonyl compounds, amines, and so on. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

Another important use for Wilkinson s catalyst is in the production of materials that are optically active (by what is known as enantioselective hydrogenation). When the phosphine ligand is a chiral molecule and the alkene is one that can complex to the metal to form a structure that has R or S chirality, the two possible complexes will represent two different energy states. One will be more reactive than the other, so hydrogenation will lead to a product that contains predominantly only one of the diastereomers. 

Further complications may arise with the larger amino acids such as isoleucine, where the R side-chain itself contains a chiral carbon atom [R = CH3CH2C H(CH)3, where the asterisk denotes the second chiral centre]. This molecule is an example of a diastereomer - a molecule with more than one chiral centre. Diastereomers have different physical and chemical properties, and their interconversion is more complicated, and is termed epimerization. 

There are two possible approaches for the preparation of optically active products by chemical transformation of optically inactive starting materials kinetic resolution and asymmetric synthesis [44,87], For both types of reactions there is one principle in order to make an optically active compound we need another optically active compound. A kinetic resolution depends on the fact that two enantiomers of a racemate react at different rates with a chiral reagent or catalyst. Accordingly, an asymmetric synthesis involves the creation of an asymmetric center that occurs by chiral discrimination of equivalent groups in an achiral starting material. This can be done either by enan-tioselective (which involves the reaction of a prochiral molecule with a chiral substance) or diastereoselective (which involves the preferential formation of a single diastereomer by the creation of a new asymmetric center in a chiral molecule) synthesis. 

Chiral molecules interact to form complexes that are related as enantiomers or as diastereomers. Enantiomers are perfect chemical models for each other except in their interactions with polarized light or with other chiral molecules, and this provides the basis for an absolute method for demonstrating subtle differences in physical properties that might otherwise be confused with the effects of impurities. 

The ability of a chiral molecule to distinguish between the enantiomers of a second (different) chiral molecule was defined in Sect. II as a diastereomer discrimination. This phenomenon may be observed in a mixed monolayer of two chiral surfactants and may also occur when a chiral substance is dissolved in the aqueous subphase under the monolayer of a second chiral substance. As before, examples of such chiral discrimination would not include those whose difference in monolayer behavior results only from the gross structural differences of diastereomers such as the different force-area characteristics exhibited by mixed monolayers of l-oleoyl-2-stearoyl-3-s -phospha-tidylcholine with epimeric steroids (120). The relevant experiment, that of comparing the monolayer behavior of mixed monolayers of cholesterol with enantiomeric phospholipids, has been reported (121). As might be anticipated from our previous discussion of... 

The relevance of such a diastereomer discrimination to the transport of chiral molecules, such as pharmaceuticals or biochemicals, through hydrophobic barriers, such as cell membranes, is obvious. Furthermore, since poly(DL-lysine) followed the same general pattern of behavior displayed by the other three samples, the observed surface-pressure changes probably were not due to helicalization of the polypeptide. Whereas poly(L-lysine) and poly(D-lysine) form helices with opposite screw sense, the random copolymer poly(DL-lysine) is to a large extent prevented from forming helices. 

Stereoisomers that are not enantiomers are called diastereoisomers. Three classes may be distinguished configurational, geometrical, and conformational isomers. Configurational diastereomers include molecules with more than one chiral center. Thus 2,3-dichlorobutane can exist in three configurationally... 

Notice that 6 represents a chiral molecule and if HA and HB each are replaced with X we get 8 and 9, which are diastereomers (see Section 5-5). You can verify this with molecular models if necessary. Diastereomers have different... 

We have seen that individual enantiomers have identical physical properties and only can be distinguished in a chiral environment. Plane-polarized light is such a chiral environment, and one enantiomer is dextrorotatory and one is levorotatory. Another way to distinguish enantiomers is to allow them to react (or interact) with other chiral molecules. The interaction of a mixture of enantiomers with a single enantiomer of a chiral molecule produces a mixture of diastereomers as illustrated. 

Although the term prochirality is frequently used, especially by biochemists, it suffers from a limitation which arises from a corresponding limitation in the definition of chirality. Molecules may display purely stereochemical differences without being chiral cis-tram isomers of olefins and certain achiral cis-trans isomers of cyclanes are examples. Thus (Fig. 2) (Z)- and ( )-1,2-dichloroethylene (4, 5) are achiral diastereomers, as are cis- and /rtww-1,3-dibromocyclobutanes (6, 7) being devoid of chirality these compounds have no chiral centers (or other chiral elements). Thus it is inappropriate to associate stereoisomerism with the occurrence of chiral... 

Molecules in this section fall into two general categories those that are inherently achiral, and those that, in their most stable thermodynamic state, are racemic mixtures. All have at least one chromophore. The analytical approach is the same for both. They are made to form derivatives by reaction with a chiral host. In the case of racemates the derivatives are diastereomers and methods for their analytical applications have been referenced in earlier sections. Regardless of the distinction between racemic and non-racemic substances, the induced CD effects are uniformly smaller than the effects inherent to chiral molecules by one to two orders of magnitude. 

C Diastereomers of Molecules with Two or More Chirality Centers... 

Stereoisomers can be classified into two types enantiomers and dia-stereomers. Enantiomers (mirror images) have identical physical and chemical properties and therefore are not separated on the conventional reversed-phase stationary phases. Their separation will not be discussed. Diastereomers are isomers which are not mirror images of the parent. They have slightly different physical and chemical properties and can often be separated on conventional stationary phases. There are two classes of diastereomers optically active isomers when the API has two or more stereocenters and non-optically active geometric isomers, such as cis-trans, syn-anti, etc. Stereoisomers of chiral molecules must be included in the peak set. 

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