Stereoisomers optical

The a-carbon of each amino acid is attached to four different chemi cal groups and is, therefore, a chiral or optically active carbon atom. Glycine is the exception because its a-carbon has two hydro gen substituents and, therefore, is optically inactive. [Note Amino acids that have an asymmetric center at the a-carbon can exist in two forms, designated D and L, that are mirror images of each other (Figure 1.8). The two forms in each pair are termed stereoisomers, optical isomers, or enantiomers.] All amino acids found in proteins are of the L-configuration. However, D-amino acids are found in some antibiotics and in bacterial cell walls. (See p. 250 for a discus sion of D-amino acid metabolism.)... 

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). 

Asymmetric cyclization using chiral ligands has been studied. After early attempts[142-144], satisfactory optical yields have been obtained. The hexahy-dropyrrolo[2,3-6]indole 176 has been constructed by the intramolecular Heck reaction and hydroaryiation[145]. The asymmetric cyclization of the enamide 174 using (S j-BINAP affords predominantly (98 2) the ( )-enoxysilane stereoisomer of the oxindole product, hydrolysis of which provides the ( l-oxindole aldehyde 175 in 84% yield and 95% ec. and total synthesis of (-)-physostig-mine (176) has been achieved[146]. 

Only three not four stereoisomeric 2 3 butanediols are possible These three are shown m Eigure 7 10 The (2R 3R) and (2S 3S) forms are enantiomers of each other and have equal and opposite optical rotations A third combination of chirality centers (2R 3S) however gives an achiral structure that is superimposable on its (2S 3R) minor image Because it is achiral this third stereoisomer is optically inactive We call achiral mole cules that have chnahty centers meso forms The meso form m Eigure 7 10 is known as meso 2 3 butanediol... 

Multiple Chiral Centers. The number of stereoisomers increases rapidly with an increase in the number of chiral centers in a molecule. A molecule possessing two chiral atoms should have four optical isomers, that is, four structures consisting of two pairs of enantiomers. However, if a compound has two chiral centers but both centers have the same four substituents attached, the total number of isomers is three rather than four. One isomer of such a compound is not chiral because it is identical with its mirror image it has an internal mirror plane. This is an example of a diaster-eomer. The achiral structure is denoted as a meso compound. Diastereomers have different physical and chemical properties from the optically active enantiomers. Recognition of a plane of symmetry is usually the easiest way to detect a meso compound. The stereoisomers of tartaric acid are examples of compounds with multiple chiral centers (see Fig. 1.14), and one of its isomers is a meso compound. 

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 steric bulk of the three iodine atoms in the 2,4,6-triiodoben2ene system and the amide nature of the 1,3,5-substituents yield rotational isomers of the 5-A/-acyl-substituted 2,4,6-triiodoisophthalamides. Rotational motion in the bonds connecting the side chains and the aromatic ring is restricted. These compounds also exhibit stereoisomerism when chiral carbon atoms are present on side chains. (R,5)-3-Amino-l,2-propanediol is incorporated in the synthesis of iohexol (11) and ioversol (12) and an (3)-2-hydroxypropanoyl group is used in the synthesis of iopamidol (10). Consequendy, the resulting products contain a mixture of stereoisomers, ie, meso-isomers, or an optical isomer. 

Physical constants (2) for the optically pure stereoisomers of 2-butanol have been reported as follows ... 

Since chirality is a property of a molecule as a whole, the specific juxtaposition of two or more stereogenic centers in a molecule may result in an achiral molecule. For example, there are three stereoisomers of tartaric acid (2,3-dihydroxybutanedioic acid). Two of these are chiral and optically active but the third is not. 

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. 

By the dry distillation of trimethyl - thujylammonium hydroxide, Tschugaeff obtained a thujene quite similar to the above, but of considerably higher optical rotation. He therefore considers that two stereoisomers may result from different methods of preparation from thujone. 

The concept of using continuous chromatography for the separation of stereoisomers or optical isomers is very old and was probably proposed for the first time by Martin and Kuhn in 1941 [28]. The suggested implementation was different from today s SMB technology, though the basic concept is the same. The chromatographic media is moved continuously in a conveyor belt, the feed is injected continuously at a fixed point, and the pure enantiomers are recovered at fixed points. In the idea of Martin and Kuhn, benefits were taken from the possibility of modulating the adsorption of the products at different temperatures. 

Draw all possible stereoisomers of L,2-cyclobutanedicarboxvlic acid, and incli cate the interrelationships. Which, if any, are optically active Do the same fo 1,3-cyclobutanedicarboxylic acid. 

How many stereoisomers of 2,4-dibromo-3-chloropentane are there Draw them, and indicate which are optically active. 

Assume that you have carried out a radical chlorination reaction on (P)-2-chloro-pentane and have isolated (in low yield) 2,4-dichIoropentane. How many stereoisomers of the product are formed and in what ratio Are any of the isomers optically active (See Problem 10.24.)... 

The [2n + 2n] cycloaddition of the optically active ketene 31 to various 1,2-diazepines 30 gives mixtures of the stereoisomers 32A and 32B, in which the former predominate.79... 

Chrysanthemumic acid may exist in four stereoisomers, because of the two asymmetric carbon atoms in the cyclopropane ring. The natural acid has the D-trans configuration and this has been shown to be more insecticidally active than any of the other isomers or the racemic form. Harper et al, (4,18) have synthesized, separated, and optically resolved all of the isomers of this acid. 

Although they are built from the same numbers and kinds of atoms, structural isomers have different chemical formulas, because the formulas show how the atoms are grouped in or outside the coordination sphere. Stereoisomers, on the other hand, have the same formulas, because their atoms have the same partners in the coordination spheres only the spatial arrangement of the ligands differs. There are two types of stereoisomerism, geometrical and optical. 

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