MOLECULES WITH TWO OR MORE STEREOGENIC CENTERS

Erythromycin has 18 chiral centers. Each one is designated with dashed or sohd wedge-shaped lines. The hydrogen atoms at the stereogenic centers have been omitted for clarity. 

---

Onc we grasp the idea of stereoisomerism in molecules with two or more stereogenic centers, we can explore further details of addition reactions of alkenes. 

Of course, many molecules with two or more stereogenic centers have diastereomers. Remember that every diastereomer can have a mirror image, which constitutes two stereoisomers. A molecule with two stereogenic centers will have up to two diastereomers and each will have a mirror image. This means there is a maximum total of four stereoisomers for a molecule with two... 

With two or more stereogenic centers, a molecule may or may not be chiral, as we will learn in Section 5.8. 

Diastereomers with two or More Stereogenic Centers Isomers of chiral molecules that possess two or more stereogenic centers may be either enantiomers or diastereomers. Diastereomers are not mirror images of each other. For molecules with more than one stereogenic center, the enantiomeric pair must have the opposite configuration at each center. 

More elaborate molecules can also have a plane of symmetry. For example, there are only three stereoisomers of tartaric acid (2,3-dihydroxybutanedioic acid). Two of these are chiral but the third is achiral. In the achiral stereoisomer, the substituents are located with respect to each other in such a way as to generate a plane of symmetry. Compounds that contain two or more stereogenic centers but have a plane of symmetry are called meso forms. Because they are achiral, they do not rotate plane polarized light. Note that the Fischer projection structure of meio-tartaric acid reveals the plane of symmetry. 

Going from one to two stereogenic centers in a molecule led to greater complexity with respect to the number of stereoisomers. Molecules with three or more chiral centers are even more complex, in accord with the 2" rule, where three stereogenic centers lead to a maximum of eight stereoisomers. 

Due to the more complex structures of most sesquiterpene picrotoxanes compared with the dendrobines, fewer syntheses have been reported. Their structures with up to nine stereogenic centers were too complex to be used as test molecules for newly developed reactions. Three of the syntheses reported beginning with 1979 followed new strategies (two picrotoxinin syntheses and one coriamyrtin synthesis). The other syntheses of picrotoxinin (1), picrotin (2), coriamyrtin (9), tutin (11), corianin (21), methyl picrotoxate (42), and asteromurin A (22) were extensions either of successful dendrobine syntheses or partial syntheses. Remarkably, with one exception, all the syntheses are EPC-syntheses. 

We have now seen many examples of compounds containing one tetrahedral stereogenic center. The situation is more complex for compounds with two stereogenic centers, because more stereoisomers are possible. Moreover, a molecule with two stereogenic centers may or may not be chiral. 

Besides the tetrahedral structure, the chirality of a molecule requires one additional condition all four substituents bound to the central carbon atom must be different. A carbon atom with four different substituents induces chirality of the entire molecule and is called a stereogenic, chiral or asymmetric center. If two or more substituents are identical the molecule and its mirror image can be superimposed and the molecule is not chiral. Some chiral and non-chiral molecules are represented bellow. 

Compounds in which one or more carbon atoms have four nonidentical substituents are the largest class of chiral molecules. Carbon atoms with four nonidentical ligands are referred to as asymmetric carbon atoms because the molecular environment at such a carbon atom possesses no element of symmetry. Asymmetric carbons are a specific example of a stereogenic center. A stereogenic center is any structural feature that gives rise to chirality in a molecule. 2-Butanol is an example of a chiral molecule and exists as two nonsuperimposable mirror images. Carbon-2 is a stereogenic center. 

When there is more titan one chiral center in a molecule, the number of possible stereoisomers increases. Since each chiral center can have either the R or S configuration, for a molecule of n chiral centers, there will be 2" possible stereoisomers. Thus 3-pheny 1-2-butanol has two stereogenic centers and four possible stereoisomers. These are shown below with the configuration of each chiral center designated. 

The selective enzymatic reduction of 2-substituted / -keto esters or /S-diketones is more interesting than that of unsubstituted compounds since two stereogenic centers can be introduced into the molecule in one step. The observation that baker s yeast reduction of these compounds results in predominantly one of the four possible diastereomeric products has been explained by a keto- enol equilibration of the enantiomeric / -dicarbonyls with the simultaneous removal of one of these substrates by an asymmetric reduction49. 

---