Meso compounds, also

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. 

The substituted carbons are stereogenic carbons. This means that there are not only two isomers. In the most general case, where W, X, Y, and Z are all different, there are four isomers since neither the cis nor the trans isomer is superimposable on its mirror image. This is true regardless of ring size or which carbons are involved, except that in rings of even-numbered size when W, X, Y, and Z are at opposite comers, no chirality is present, (e.g., 68). In this case, the substituted carbons are not chiral carbons. Note also that a plane of symmetry exists in such compounds. When W = Y and X=Z, the cis isomer is always superimposable on its mirror image, and hence is a meso compound, while the trans isomer consists of a dl pair, except in... 

A meso componnd has stereocenters, but the compound also has symmetry that allows it to be the mirror image of itself. Consider ds-l.T-dimethylcyclohexane as an example. This molecnle has a plane of symmetry cutting the molecule in half. Everything on the left side of the plane is mirrored by everything on the right side ... 

Meso compounds Compounds whose molecules not only have two or more centers of dissymmetry but also have plane(s) of symmetry. They do not exist as enantiomers, for example, mem-tartaric acid ... 

Let us take the hydrogenation of a cis alkene in presence of a catalyst. Because the attacking particle on both the carbon atoms is the same and the alkene is also cis, as expected we get a meso compound. 

Resistance to hydration was elucidated with tricyclic model compounds that lack the side chain and, hence, pharmacological activity. In this context, a useful comparison has been made between two meso compounds, namely 5W-dibenz.oja, dIcycloheplene 10,11-oxide (10.130, X = CH2) and d.v-slilbcnc oxide (10.7) [195]. The former compound proved to be a very poor substrate for rabbit liver microsomal EH, with a Km value comparable to that of cis-stilbene oxide, but Emax ca. 100-fold lower. This indicates that the two compounds have a comparable affinity for the enzyme, but that nucleophilic attack in the catalytic step is much less efficient for dibcnzo[ // cycloheplcnc 10,11-oxide than for d.v-slilbcnc oxide. This implies that the former compound acts better as an inhibitor than as a substrate of microsomal EH. Furthermore, there was also a fundamental steric difference in the reaction course of the two substrates, since the predominant stereoisomer formed from dibenzo //]cyclohep(ene 10,11-oxide had the (I OS, 11. -configuration,... 

The opposite case is also worthy of consideration. cis-2,3>Epoxybutane is a meso compound but the two halves of the molecule, and particularly the two O—CH(CH3) bonds, are not equivalent but enantiotopic. Ring opening polymerization occurring selectively on one of the bonds converts the R, S) monomer into a succession of monomer units (R, / )—(/ , R)— and so on, or —(5, S)—(S, S)— and so on. A chiral initiator can effect an enantiotopic differentiation (281) and thus give rise to an optically active polymer with an excess of (R, R) or (S, S) units (81, 82). 

A meso compound has a specific rotation of polarised light of 0°. A racemate is an equimolar mixture of two enantiomers and its specific rotation is also 0°. 

R)-2-Chlorobutane (I) forms free radicals (III and IV) which are conformational diasiereomers with different stabilities and populations. This is also true of I s enantiomer II. (S)-2-chlorobutane. which gives free radicals V and VI. The more stable free-radical conformers are IV and V because their CH, s are anrMike. The transition states for Cl abstractions arising from conformations IV and V have lower SH values than the diastereomeric transition states from the more crowded gauc/te-like conformations. Ill and VI. The major product is therefore the meso compound. VIII = IX. 

Double Sharpless epoxidation was also applied to the synthesis of a key intermediate 10 to the meso-compound 11 that is related to teurilene, abioactive polycyclic triterpene isolated from red alga Laurencia obtusa,4 The reaction of ( , )-Bisallylic alcohol 9 gave the bisglycidic alcohol 10 with 80% de and 89% ee for each epoxidation (Scheme 6AA.4). 

In achiral media, different NMR spectra are expected for each of the four types of enantiomeric pairs and for the two meso compounds. In general, because of the synthetic approach, the ratio of cis- to /nmv-rcsiducs is about three, which, assuming that quaternisation at one tetrahydroisoquinoline residue does not affect quaternisation at the other, leads to proportions of cis-cis, cis-trans and trans-trans isomers in the approximate ratio of 11 6 1. The preference for cis-residues has been proved by using nuclear Overhauser effect NMR measurements and by X-ray crystallography on related substances [37,38]. The H NMR chemical shifts, principally of the H8 proton, can be affected not only by whether the C1-N2 configuration in the residue is cis or trans but also by the configuration of the remote tetrahydroisoquinoline unit. 

The stereochemistry of the product of a reaction will be influenced by the structures of the reagent and substrate and the mechanisms by which they react. For example, the hydroxylation of but-2-ene by osmium tetroxide and water yields a racemate whilst bromination of the same compound with bromine produces a meso compound (Figure 10.5). Flowever, a stereoselective reaction is most likely to occur when steric hindrance at the reaction centre restricts the approach of the reagent to one direction (Figure 10.6). Furthermore, the action of both enzyme and non-enzyme catalysts may also be used to introduce specific stereochemical centres into a molecule. 

The cw-alkene B is consequently the major product of the olefination of Figure 11.21. It can be separated chromatographically from the minor cw-alkene iso-B and also from the fraws-alkenes formed in small amounts because these species are diastereomers. Finally, the chiral auxiliary can be removed reductively from the obtained pure alkene B (cf. the analogous reaction at the bottom of Figure 11.19). The resulting allyl alcohol C is 100% enantiomerically pure. Figure 11.21 thereby gives an example of the conversion of a meso-compound into an enantiomerically pure substance a 100% yield is possible in principle in such reactions. 

Chiral diols have also been prepared starting from meso-compounds [68-71]. Since meso-compounds are, in essence, symmetric molecules, the same applies as for the other symmetric starting materials. Indeed, this is exactly what was found Even though the stereocenters of the protected heptane tetrol are far away from the ester groups that are to be hydrolysed stereoselectively, this is what happens [69, 70]. The high selectivity is partly due to the fact that the secondary alcohol groups are protected as a cyclic acetal, giving additional structural information to the enzyme (Scheme 6.20 A). A cyclic acetal also provides additional structural information in the enantioselective hydrolysis of a pentane tetrol derivative (Scheme 6.20 B) [71]. In both cases Pseudomonas fluorescens lipase (PFL) proved to be the enzyme of choice. 

Pentanediol can also exist as a pair of enantiomers (2RAR) and (25,45) that are not meso compounds. 

Commercial 2,4-pentanediol is a mixture of three stereoisomers (R,R), (S,S), and (R,S). The meso isomer shows three signals in its 13C NMR spectrum. Its diastereomers, the R,R and S,S enantiomeric pair, also show three signals, but two of these signals occur at different 8 values from the meso isomer. This is expected, because diastereomers differ in physical and chemical properties. One resonance from the meso compound accidentally overlaps with one signal from the enantiomeric pair. 

Of the nine stereoisomers of inositol, the scyllo-isomer has no axial hydroxyl, the myo-isomer has one, the epi-, chiro-, and neo-isomers have two, and the alio-, cis-, and mneo-isomers have three hydroxyl groups (Figure 1). Of these, six isomers scyllo-, myo-, epi-, neo-, cis-, and mr/co-i somers) have one or more planes of symmetry in the molecule (meso compounds) and are therefore not chiral. D-chiro- and L-e/u>o-i somers do not have a plane of symmetry and are chiral molecules moreover they are enantiomers of each other. The alio-isomer is unique - the conformational isomer of (10) (Figure 2) is (11) which is also its enantiomer Since interconversion between conformational isomers is rapid, a//o-inositol exists as a 50/50 mixture of the two enantiomers at room temperature. Therefore, although alio-inositol is chiral, the compound is optically inactive at room temperature because it is a racemic mixture a chiral reagent, such as an enzyme, would be expected to preferentially react with one enantiomer and not the other. 

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