Stereoisomerism asymmetric carbon atoms

Stereoisomerism in the Cinchona Bases It was at first common practice to number the four asymmetric carbon atoms indicated in the general formula (I), 1, 2, 3 and 4, but this is now replaced by the more general system introduced by Rabe, who suggested the name ruban for (HI), which can be regarded as the parent substance of the natural cinchona alkaloids, and rubatoxan (IV) for that of the quinicines (quinatoxines). The formifiae, with notation, for ruban (III) and rubatoxan (IV) are shown below, and the general formula (I) for cinchona bases has been numbered in accordance with that scheme. 

A second question of general importance relates to the quantities in which the two stereoisomeric products are obtained on the generation of a new asymmetric carbon atom. Starting with nonracemic optically inactive starting materials, only racemic products are... 

On the other hand let us study the case of 2 chloro 3 hydroxy succinic acid which has two asymmetric carbon atoms and which are not identical. This compound exists in four stereoisomeric forms as predicted by 22 formula. The various projection formula are ... 

Since all the molecules are asymmetric and have no plane of symmetry, all are optically active. Further structures I and II are enantiomorphs and so are structures III and IV. But structures III and I or IV and I are although stereoisomers but are not enantiomorphs. Such pairs of steroisomers which possess chirality but are not the mirror images of each other are called diastereomers. Thus III and IV are diastereomers of 1. So diastereomers will always be formed when the compound contains two dissimilar asymmetric carbon atoms and will exist in four stereoisomeric forms. 

Therefore it should exist in eight stereoisomeric form according to 23. But since the asymmetric carbon atoms are identical, the number of active forms would be less than eight. It exists in two active and two meso forms. 

So for a molecule with two different asymmetric carbon atoms we will have not more than four stereoisomeric forms. Similarly other cyclic molecules show a similar stereoisomerism. However, with even-numbered rings certain molecules show only geometrical isomerism as in 1-methyl-3 -chlorocyclobutane. 

The dissection of a molecular model into those components that are deemed to be essential for the understanding of the stereochemistry of the whole may be termed factorization (9). The first and most important step toward this goal was taken by van t Hoff and Le Bel when they introduced the concept of the asymmetric carbon atom (10a, 1 la) and discussed the achiral stereoisomerism of the olefins (10b,lib). We need such factorization not only for the enumeration and description of possible stereoisomers, important as these objectives are, but also, as we have seen, for the understanding of stereoselective reactions. More subtle differences also giving rise to differences in reactivity with chiral reagents, but referable to products of a different factorization, will be taken up in Sect. IX. 

The polymerization of enantiomerically pure monomers presents no relevant stereochemical problems when the asymmetric carbon atom is not involved in the reaction and no new centers of stereoisomerism are formed. This is the case, for example, in polycondensation of chiral diacids with diamines (274) and in ring-opening polymerization of substituted lactams (275) and A -carboxyanhy-drides of a-amino acids (276). Interest here lies mainly in the properties of the polymer. Accidental racemization may sometimes occur but is not necessarily related to the mechanism of polymerization. 

As this compound contains two asymmetric carbon atoms, four stereoisomeric forms are possible by synthesis these must occur in two inactive forms. These forms Leuchs separated by crystallisation of the copper salts, the more insoluble acid being termed (a)-7-oxy-proline, the other (b)-7-oxyproline. 

Pyrrolizidine derivatives with at least one substituent, and particularly the pyrrolizidine alkaloid components, have one or more asymmetric carbon atoms. The stereochemistry of pyrrolizidine was clarified for the most part in the course of investigation of the naturally occurring pyrrolizidine alcohols. Here, the problems of relative and absolute configuration and of stereoisomeric transformations will be considered. 

Two structures that constitute a stereoisomeric pair are referred to as enantiomers. The two enantiomers for alanine are illustrated in figure 3.8. These two isomers are called L-alanine and D-alanine, according to the way in which the substituents are arranged about the asymmetric carbon atom. The naming by D and l (for dextrorotatory and levorotatory see chapter 6) refers to a convention established by Emil Fischer many years ago. According to this convention all amino acids found in proteins are of the l form. Some D-amino acids are found in bacterial cell walls and certain antibiotics. 

Any molecule with n asymmetric carbon atoms can exist in the form of 2 stereoisomers including 2W enantiomeric (mirror image) pairs. When the number of asymmetric carbon atoms exceeds two, so-called dia-stereoisomeric forms become possible. They possess different physical properties and are not mirror images. Enantiomers, however, are identical in physical properties with the exception of their behavior toward polarized light. The aldohexoses comprise 16 stereoisomers (8 enantiomeric pairs) belonging to the respective series. Within the d or l series the individual aldohexoses are diastereoisomers. The aldoses in D series are shown in Fig. 2-3. 

The molecular helices and propellers discussed above contain no center of chirality, and the P and M nomenclature is thus the only way of describing their absolute configuration. This nomenclature, however, is also applicable to some series of chiral compounds which display several centers of chirality. As will be discussed in Section 6, the presence in a molecule of two or more centers of chirality usually implies the existence of several stereoisomers, but steric reasons may reduce down to two the possible number of stereoisomeric forms. Thus, 2,3-epoxycyclohexanone contains two asymmetric carbon atoms, but for steric reasons only two stereoisomers, namely the (2S 3S)-(—)- and the (2/ 3/J)-( + )-enantiomer, exist the former is depicted in diagram XL [49]. 

Stereoisomerism occurs in vinyl polymers when one of the carbon atoms of the monomer double bond carries two different substituents. It is formally similar to the optical isomerism of organic chemistry in which the presence of an asymmetric carbon atom produces two isomers which are not superimposable. Thus glyceraldehyde exists as two stereoisomers with configurations shown in 4-13. (The dotted lines denote bonds below and the wedge signifies bonds above the plane of the page.) Similarly, polymerization of a monomer with structure... 

It is of paramount importance to look for stereochemistry-related compounds, i.e., those compounds that have similar chemical structure but different spatial orientation. These compounds can be considered impurities in the API. Included in this group are various stereoisomers. The simplest case of chirality can be seen in a molecule that has one or more tetrahedral carbons with four different substituents (asymmetric carbon atom) such that its mirror image is not superimposable. Chiral molecules may also occur for a number of other reasons and must be factored into any evaluation of impurities.10-12 Stereoisomerism is possible in molecules that have any of the following characteristics ... 

Menthol (1-methyl-4-isopropylcyclohexan-3-ol) is a monocyclic monoterpenoid, which possesses three asymmetric carbon atoms and therefore exists in eight stereoisomeric forms as shown in Figure 4.23. 1-Menthol is the most highly desired of these since it produces a physiological cooling effect. That is, when applied to skin or mucus membranes, 1-menthol creates the sensation of cooling independent of the... 

One problem with a special emphasis in the pharmaceutical industry involves the isolation of stereoisomers (optical isomers). An organic molecule with no asymmetric carbon atoms is denoted as achiral, but if it contains one or more asymmetric carbon atoms, it would be denoted as a stereoisomer. If a single asymmetric carbon exists, there will be two enantiomers, while with two asymmetric carbon atoms the molecule forms four diastereomers. A reader not familiar with the general concept of steriochemistry should refer to a introductory organic chemistry text. Biological systems are inherently based on enantiomeric or stereoisomeric biochemistry. Thus, there has been a trend toward selecting a single stereoisomer as a new chemical entity for pharmaceuticals (Collins et al. 1997 Stinson 1999). 

If a molecule has two asymmetric carbon atoms, provided that these are non-identical, there can be four possible stereoisomeric forms, and hence two completely different racemates. The relationship between an enantiomer from... 

For the classification of ordered or regular polymers, we shall be concerned only with stereoisomerism in the main chain. In the main chain, or, as is sometimes said, the backbone of the polymer, two kinds of stereoisomerism can exist. The first arises from asymmetric carbon atoms in the chain, and the second from double bonds that form part of the links in the backbone. The backbone is thus made up of repeating units, each of which can be a source of stereoisomerism. If the units are disposed in an ordered way we have what is called a tactic polymer. This will later be defined more specifically. 

The other factor that can seriously affect crystallinity is stereoisomerism, which occurs in polymers that contain asymmetric carbon atoms, that is, carbon chain atoms having both a hydrogen atom and another group R ... 

In the same year he received his doctor s degree, he pubhshed the first explanation of optical activity based on the stereoisomerism of an asymmetric carbon atom. Similar ideas were pnblished independently two months later by the French chemist Joseph Le Bel. 

It is possible for stereoisomerism to exist among certain polymers that have chemically identical chain repeating units. The concentration and sequence distribution of the stereoisomers along the chain have an important bearing on the crystallization and melting of such polymers. An important class of polymers possessing asymmetric or pseudo-asymmetric carbon atoms are those that adhere to the general formula... 

Flavanones are 2,3-dihydroflavones, while flavanonols are 2,3-dihydroflavonols. Indeed, flavanols are also termed dihydroflavonols and individual members may be named both from the plant source and from the derived flavonoL The most common flavanonol, for example, is known both as dihydroquercetin and as tax-ifolin. Reduction of the 2,3-double bond introduces an asymmetric carbon atom at C-2 and flavanones are capable of existing in two stereoisomeric forms. In fact, most if not all naturally occurring flavanones are laevorotatory and probably belong to the same (2S) configurational series. This has been proved rigorously for (-)-liquiritigenin (24). 

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