Stereoisomers recognizing

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

Stereoselectivity, in particular, enantioselectivity, is the most important feature of enzymes. It should be stressed that enzymes are capable of recognizing any type of chirality of the substrates. It does not seem necessary to prove here how important the synthesis of sterically defined products is, because the differences in biological activity of particular stereoisomers of a given substance are well known. There are three approaches to the synthesis of enantiomerically enriched... 

The importance of the three stereogenic centers became evident as two of the stereoisomers [(2S,3S,7S) and (2S,3R,7R)] were recognized early as sex pheromones and that other enantiomers and diastereoisomers were often found to be inhibitory to the attractive response. Recently, the sawfly pheromone field has undergone a major advance with the recognition that several sawfly species synthesize and utilize sex pheromones of different structural types than the 3,7-dimethylpentadecan-2-ols. Shorter and longer chain lengths (undecan-2-ols 2 and tridecan-2-ols 3) and an additional methyl group in position 9 or 11 (4 and 5) characterize these new pheromone discoveries (Fig. 1). With an ad-... 

To see why this is important, consider a butene (2-butene) in which the double bond is between the two central carbon atoms CH3—CH—CH—CH3. If we think about it for a bit, we can recognize that there are really two of these structures they are stereoisomers that are not enantiomers and not constitutional isomers. Such stereoisomers are termed diastereomers. Diastereomers in this class are also known by the older and largely obsolete term geometrical isomers. They differ in the way that the two methyl groups at the ends of the molecule are disposed with respect to each other. The two possibilities are ... 

Stereoisomers, on the other hand, are compounds with the same molecular formula, and the same sequence of covalently bonded atoms, but with a different spatial orientation. Two major classes of stereoisomers are recognized, conformational isomers and configurational isomers. 

By definition, it is necessary to recognize geometric isomers, isotopomers and stereoisomers as distinct species. Moreover, there is the pragmatic issue that regio-selectivity, isotopic labeling and stereo-chemical investigations are three very important avenues of mechanistic enquiry. 

Figure 1.11 Stereoisomers a carbon atom bonded to fonr different substituents in a chiral carbon or a stereogenic center. Such molecules cannot be superimposed upon their mirror image. A receptor will recognize one stereoisomer but not another. Such stereoisomers are designated as either R or S. Stereoisomerism may also occur around double bonds, producing cis or trans orientations of the substituents on either face of the double bond.

All of the threonine stereoisomers 19-22 are chiral substances that is, they are not identical with their mirror images. However, it is important to recognize that not all diastereomers are chiral. To illustrate this point, we return to the tartaric acids mentioned previously in connection with Pasteur s discoveries (Section 5-1C). 

The enantiomeric separation of the D- from the L-stereoisomers of amino acids is an area of growing interest. It is generally recognized that heat- and alkali-treatment of proteins can result in the racemization of L-isomers of amino acid residues to the D-analogs. Almost without exception, humans cannot utilize the D-isomers of amino acids, and some are thought to be toxic (although... 

The desired synthetic route becomes apparent when it is recognized that the Z alkene stereoisomer may be obtained from an alkyne, which, in turn, is available by carboxylation of the anion derived from the starting material. 

At the instant Pasteur recognized the existence of stereoisomers (objects), he also accepted the existence of stereoprocesses (operations). For the notion of isomer carries with it criteria of distinguishability among these is the possibility that a given isomer can be formed, separated, or altered in a way which differentiates it from other isomers. This applies equally to isomers with many properties in common, e.g. optical antipodes, or to those with essentially all different properties, e.g. cis-trans, syn-anti, gauche-anti, erythro-threo, or axial-equatorial pairs. Now, the stereo-path may be part of an overall conversion which, if described in some detail, we term a mechanism. Our present task is to attempt to understand those elementary or single-step processes by which stereochemical choices are made. 

This chapter introduces a new type of stereoisomer, the most subtle that we will encounter. This type of stereoisomer arises because of the tetrahedral geometry of singly bonded carbon. After this stereoisomerism is described, a discussion of how to recognize when these stereoisomers occur is presented. Next, a method to designate the configuration of these stereoisomers is described. After a discussion of when their properties differ, more complex examples are described. Finally, how they are prepared and how they are separated are considered. 

We may divide the large number of known cases (and the even greater number of hypothetical cases) of inorganic isomerism into two very broad classes (1) position isomers having the same sets of atoms but different sets of bonds (as is the ease with ethyl alcohol and dimethyl ether) and (2) stereoisomers having the same atoms, the same sets of. bonds, but differing somehow in the orientation of these bonds. Werner and many workers after him recognized a number of subclasses of position isomerisms. 

Isomerism types of isomerism in organic compounds, and we will cover them in detail in Chapter 5 (Stereochemistry). For now, we need to recognize the two large classes of isomers constitutional isomers and stereoisomers. 

Recognize structures that have stereoisomers, and identify the relationships between the stereoisomers. 

You ve probably recognized that there s a simple mathematical relationship between the number of stereogenic centres and the number of stereoisomers a structure can have. Usually, a structure with n stereogenic centres can exist as 2 stereoisomers. These stereoisomers consist of 2 diastereoisomers, each of which has a pair of enantiomers. This is an oversimplification to be used cautiously because it works only if all diastereoisomers are chiral. We recommend that you find out how many diastereoisomers there are in every new molecule before considering enantiomers. 

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