Configurational isomers stereoisomerism

Isomeric alkenes may be either constitutional isomers or stereoisomers There is a sizable barrier to rotation about a carbon-carbon double bond which corresponds to the energy required to break the rr component of the double bond Stereoisomeric alkenes are configurationally stable under normal conditions The configurations of stereoisomeric alkenes are described according to two notational systems One system adds the prefix CIS to the name of the alkene when similar substituents are on the same side of the double bond and the prefix trans when they are on opposite sides The other ranks substituents according to a system of rules based on atomic number The prefix Z is used for alkenes that have higher ranked substituents on the same side of the double bond the prefix E is used when higher ranked substituents are on opposite sides... 

French scientists (270) suggested that the configurations of stereoisomeric acyclic alkyl nitronates can be determined from the relative dipole moments which for trans- isomers of nitronates containing EWG at the a-C atom are substantially larger than those of the cis isomers (Chart 3.5). 

Stereoisomers have the same order of atom attachments but different arrangements of the atoms in space. Cis-trans isomerism is one kind of stereoisomerism. For example, two substituents on a cycloalkane can be on either the same (c/s) or opposite (trans) sides of the mean ring plane. Stereoisomers can be divided into two groups, conformational isomers (interconvertible by bond rotation) and configurational isomers (not interconvertible by bond rotation). Cis-trans isomers belong to the latter class. 

D-configurational isomers — however, only 1-amino acids are found in proteins. The reader must be aware that such stereoisomerism is indicated in some key examples but not in all cases for reasons of space and didactic effectiveness. 

The reader should note that stereoisomerism does not exist if the substituents X and Y in the monomer 4-14 are identical. Thus there are no configurational isomers of polyethylene, polyisobutene, or polyfvinylidene chloride). It should also be clear that 1,2-poly-butadiene (reaction 4-3) and the 1,2- and 3,4-isomers of polyisoprene can exist as isotactic, syndiotactic. and atactic configurational isomers. The number of possible structures of polymers of conjugated dienes can be seen to be quite large when the possibility of head-to-head and head-to-tail isomerism is also taken into account. 

Conformational isomers (conformers) are stereoiso-meric forms characterized by different relative spatial arrangements of atoms that result from rotation about sigma bonds. Thus, unlike configurational isomers, conformers are interconverting stereochemical forms of a single compound. The nature of conformational and configurational stereoisomerism, as well as the role of stereoisomerism in drug activity is the subject of this article. 

A second type of isomerism is stereoisomerism. Stereoisomers have the same molecular formula and the same connectivity but different orientations of their atoms in space. One example of stereoisomerism we have seen thus far is that of cis,trans isomers in cycloalkanes (Section 2.6), which arise because substituents on a ring are locked into one of two orientations in space with respect to one another by the ring. Isomers of this type are called configurational isomers because they differ by the configuration of substituents on an atom. 

Here we introduce a further category of isomerism known as stereoisomerism, in which the molecules concerned have the same molecular formula and structural formula, but their atoms are arranged differently in space. There are three types of stereoisomerism — conformational isomerism, cis— trans isomerism and optical isomerism (Figure 20.46). Configurational isomers have permanent Figure 20.46 The different types of isomerism differences in their structural geometry and cannot... 

Configurational Stereoisomerism Configurational isomers are stereoisomers that do not readily interconvert under normal conditions and thus can be separated and isolated. Interconversion in these stereoisomers usually... 

Diastereomers include all stereoisomers that are not related as an object and its mirror image. Consider the four structures in Fig. 2.3. These structures represent fee four stereoisomers of 2,3,4-trihydroxybutanal. The configurations of C-2 and C-3 are indicated. Each stereogenic center is designated J or 5 by application of the sequence rule. Each of the four structures is stereoisomeric wife respect to any of fee others. The 2R R and 25,35 isomers are enantiomeric, as are fee 2R, iS and 25,3J pair. The 21 ,35 isomer is diastereomeric wife fee 25,35 and 2R,3R isomers because they are stereoisomers but not enantiomers. Any given structure can have only one enantiomer. All other stereoisomers of feat molecule are diastereomeric. The relative configuration of diastereomeric molecules is fiequently specified using fee terms syn and anti. The molecules are represented as extended chains. Diastereomers wife substituents on the same side of the extended chain are syn stereoisomers, whereas those wife substituents on opposite sides are anti stereoisomers. 

A third type of configurational interdependence exists if two elements are so interrelated that a change in the configuration of one automatically alters that of the other. This characterization applies to the two centers of 1,4-cyclohexanediol of the type Cg+g hi (5,51). Consequently only two isomers exist and a single pair of descriptors suffices for their distinction. We can remove the mutual dependence of the two elements by waiving the requirement that a line of stereoisomerism be occupied by bonds. The H and OH ligands have different distributions in the isomers about the line between C(l) and C(4), and the usual terms cis and trans express this relationship. Undoubtedly this is the most convenient description and the only one now available, but should we go further and say that the proper element of stereoisomerism in this case is this achiral line of torsion, and that its further factorization into two graphochiral centers is unwarranted ... 

A second problem that has repeatedly concerned us is the inability of the Sequence Rule to provide descriptors for some elements of stereoisomerism. When Cahn et al. (16) first encountered this problem with the all-cis and all-trans isomers of inositol, they attributed it to the fact that the symmetry has become so high that they have no asymmetric, nor even a pseudo-asymmetric atom. This interpretation, we believe, is incorrect. If the two ring ligands of any carbon atom of m-inositol were not heteromorphic, their exchange could not yield an isomer, as it clearly does. Each atom is a center of stereoisomerism with a pair of enantiomorphic ligands (Cg+g hi) and indistinguishable from the traditional pseudoasymmetric atom. The description of cu-inositol as all-5 could be accomplished by the same device that would allow one to specify the configurations of C(l) and C(4) of 4-methylcyclohexanol. 

The challenge lay in the stereochemicaUy correct synthesis of the polyketide part of the molecule. Starting from L-serine (89) (Chart 6) by C2-elongation steps, reduction of the obtained keto functions including adequate protection and deprotection, and introduction of the salicylic acid residue the four stereoisomeric 3,5-diols (90) were obtained. Comparison of the H-NMR data with those of anachelin (10) showed that the isomer with 3R,5S,6S) configuration was the correct starting material. 

The stereochemical outcome of epoxidation of 6-suhstitiited 2-al-koxy-5,6-dihydro-2/i-pyrans with peroxy acids is dependent on the configuration and on the type of substituents in the substrate from either isomer, the cis or trails, or (usually) both, stereoisomeric epox-idc(s) are formed. In the case of the Irons isomer, the a-lijxo epoxide (232) preponderates over the a-ribo compound (233). From thee/.v iso-... 

Both tosylhydrazones95-287-288 and oximes289 292- 336 were formed in good yields from the corresponding cyclobutanones under standard conditions. The tosylhydrazone of 4-isopropyli-dene-7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one was reported288 to first crystallize at — 20 °C as a thermally labile stereoisomer which isomerized to a 1 5 mixture of the two possible stereoisomeric hydrazones 1 at room temperature. In deuteriochloroform at room temperature, the half life of the least stable isomer was approximately 8 hours. The exact configuration of each stereoisomer was not stated. 

Now we do know. X-ray crystallographic studies in 1951 confirmed that the levorotatory and dextrorotatory forms of tartaric acid are mirror images of each other at the molecular level and established the absolute configuration of each (Fig. 1). The same approach has been used to demonstrate that although the amino acid alanine has two stereoisomeric forms (designated d and l), alanine in proteins exists exclusively in one form (the l isomer see Chapter 3). 

It can be seen that the cation radical of stilbene, but not stilbene itself, is subjected to acetoxylation. Stilbene in trans form yields the trans form of the cation radical, which undergoes further reaction directly. Stilbene in cis form gives the cation radical with the cis structure. Such a cis cation radical at first acquires the trans configuration and only after that adds the acetate ion. It is the isomerization that causes the observed retardation of the total reaction. It is the absence of adsorption at the electrode surface that allows the nonace-toxylated part of cis stilbene to isomerize and to turn into the more rich stereoisomeric set of final products. To support this point of view, one can mention the cation radical epoxi-dation and cylopropanation of stilbenes. In the aminiumyl ion-catalyzed reactions, cis stil-benes react about 2.5 times slower than trans stilbenes, whereas in electrophilic oxidations the cis isomers are more reactive (Kim et al. 1993 Bauld Yeuh 1994 Mirafzal et al. 1998 Adamo et al. 2000). 

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