Asymmetric centers isomers with

When the asymmetric carbon atoms in a chiral compound are part of a ring, the isomerism is more complex than in acyclic compounds. A cyclic compound which has two different asymmetric carbons with different sets of substituent groups attached has a total of 2 = 4 optical isomers an enantiometric pair of cis isomers and an enantiometric pair of trans isomers. However, when the two asymmetric centers have the same set of substituent groups attached, the cis isomer is a meso compound and only the trans isomer is chiral. (See Fig. 1.15.)... 

D-Methylmalonyl-CoA, the product of this reaction, is converted to the L-isomer by methylmalonyl-CoA epunerase (Figure 24.19). (This enzyme has often and incorrectly been called methylmalonyl-CoA racemase. It is not a racemase because the CoA moiety contains five other asymmetric centers.) The epimerase reaction also appears to involve a carbanion at the a-position (Figure 24.20). The reaction is readily reversible and involves a reversible dissociation of the acidic a-proton. The L-isomer is the substrate for methylmalonyl-CoA mutase. Methylmalonyl-CoA epimerase is an impressive catalyst. The for the proton that must dissociate to initiate this reaction is approximately 21 If binding of a proton to the a-anion is diffusion-limited, with = 10 M sec then the initial proton dissociation must be rate-limiting, and the rate constant must be... 

Molecules that contain two or more asymmetric centers exist in more than two stereoisomeric forms. Some are pairs of optically active isomers others may be symmetric and therefore optically inactive. An example is tartaric acid with two asymmetric central carbon atoms. It has three isomers, two of which are optically active and one inactive. 

Asymmetric hydrosilation of prochiral olefins other than 1,1-disubsti-tuted ones was unsuccessful because they were unreactive under the conditions employed. Styrene afforded a 20% yield of 1-phenylethyl- and 50% of 2-phenylethylmethyldichlorosilane, both inactive. The 1-phenylethyl isomer had a possibility of activity with its asymmetric center, PhMeC HSi=. 

In 1894, Fischer wrote "It will probably be possible to obtain all riiem-bers of the sugar group by a combination of the cyanohydrin reaction with the reduction of lactones, as soon as we have succeeded in finding the two optically active forms of glyceraldchyde. All observations agree with the isomerisms foreseen by Van t Hoff, above all the disappearance of isomers if the molecule becomes constitutionally symmetric. This includes the transformation of different stereoisomers into one and the same substance if one of several asymmetric centers is abolished." An example of this is... 

The stereospecificity of living organisms is imperative to their efficiency. The reason is that it is just not possible for an organism to be so constructed as to be able to deal with all of the theoretically possible isomers of molecules with many asymmetric centers. Thus a protein molecule not uncommonly has 100 or more different asymmetric centers such a molecule would have 2100 or 1030 possible optical isomers. A vessel with a capacity on the order of 107 liters would be required to hold all of the possible stereoisomeric molecules of this structure if no two were identical. An organism so constituted as to be able to deal specifically with each one of these isomers would be very large indeed. 

When an asymmetric center is present in a compound, it is thought that the substituents on the chiral carbon atom make a three-point contact with the receptor. Such a fit insures a very specific molecular orientation which can only be obtained for one of the two isomers (Fig. 1.3). A three-point fit of this type was first suggested by Easson and Stedman [23], and the corresponding model proposed by Beckett [24] in the case of (R)-( )-adrenaline [= (R)-( )-epinephrine]. The more active natural (R)-( )-adrenaline establishes contacts with its receptor through the three interactions shown in Fig. 1.3. 

As seen in the structure, moxalactam disodium has three asymmetric centers. Two centers in the ring system, C6 and C7, are stereospecifically defined during the biosynthesis of the penicillin used to produce the compound. A third asymmetric center exists adjacent to the amide carbon on the side chain of the antibiotic. The configuration of this center is free to equilibrate and thus a pair of diasterioisomers is possible for moxalactam disodium. The rate of interconversion between the isomers increases with increasing acidity, with the maximum rate occurring at a pH of about 2.5. For solutions with pH lower than 2.5, the rate of interconversion is decreased only slightly from the maximum rate. 

The most striking feature in diastereoisomerism of metal complexes is the very rapidly growing number of isomers, by introducing different elements of chirality in the basic framework of a coordination compound. The complex formation with l,8-diamino-4-methyl-3,7-diazaoctane (5-Metrien) for example — a ligand with a single asymmetric center — leads not only to four geometric isomers. Three of these show a structure containing all four types of chiral elements mentioned, so that the system offers 28 possibilities of isomers. 

In the amides marked with there has been the introduction of a new asymmetric center, which of course doubles the number of isomers that is possible. In each case the resulting two optical forms were prepared separately, and evaluated separately as to their pharmacology. 

White peach scale. Several scale sex pheromones have now been elucidated each of them possesses an asymmetric center and usually a trisubstituted alkene link within an isoprenoid framework (43). The structure of the white peach scale pheromone, R,Zb-II (Figure 8), lent itself to synthesis with another chiral starting material, namely limonene (44). Selective ozonlysis followed by workup with dimethyl sulfide-methanol provided a ketoacetal, III. Wittig methylenation followed by hydrolytic cleavage of the acetal gave a dienaldehyde, IV. Conversion of the aldehyde via the acid to an amide (45) with enantiomerically pure ot-methylbenzylamine permitted chromatographic assessment of the purity of the diene aldehyde (and the limonene). The required R-isomer of the diene aldehyde was >48% ee. 

---