Prochirality center

It is generally beheved that selectivity of hydrolytic enzymes strongly depends on the proximity of the chiral center to the reacting carbonyl group, and only a few examples of successful resolutions exist for compounds that have the chiral center removed by more than three bonds. A noticeable exception to this rule is the enantioselective hydrolysis by Pseudomonasfluorescens Hpase (PEL) of racemic dithioacetal (5) that has a prochiral center four bonds away from the reactive carboxylate (24). The monoester (6) is obtained in 89% yield and 98% ee. 

The two protons at C-1 are topologically nonequivalent, since substitution of one produces a product tiiat is stereochemically distinct fiom that produced by substitution of the other. Ligands of this type are termed heterotopic, and, because the products of substitution are enantiomers, the more precise term enantiotopic also applies. If a chiral assembly is generated when a particular ligand is replaced by a new ligand, the original assembly is prochiral. Both C-1 and C-3 of 1,3-propanediol are prochiral centers. 

Chiral chemical reagents can react with prochiral centers in achiral substances to give partially or completely enantiomerically pure product. An example of such processes is the preparation of enantiomerically enriched sulfoxides from achiral sulfides with the use of chiral oxidant. The reagent must preferential react with one of the two prochiral faces of the sulfide, that is, the enantiotopic electron pairs. 

If a tetrahedral center in a molecule has two identical substituents, it is referred to as prochiral since, if either of the like substituents is converted to a different group, the tetrahedral center then becomes chiral. Consider glycerol the central carbon of glycerol is prochiral since replacing either of the —CH9OH groups would make the central carbon chiral. Nomenclature for prochiral centers is based on the (R,S) system (in Chapter 3). To name the otherwise identical substituents of a prochiral center, imagine... 

The carbonyl carbon of an unsymmetrical ketone is a prochiral center reaction with a Grignard reagent 2 (R 7 R, R") can take place on either face of the carbonyl group with equal chance. The products 8a and 8b are consequently formed in equal amounts as racemic mixture, as long as no asymmetric induction becomes effective ... 

In addition to compounds with planar, sp2-hybridized carbons, compounds with tetrahedral, sp3-hybridized atoms can also be prochiral. An vp3-hybridizec) atom is said to be a prochirality center if, by changing one of its attached groups, it becomes a chirality center. The —GH2OH carbon atom of ethanol, for instance, is a prochirality center because changing one of its attached -H atoms converts it into a chirality center. 

Elucidating the stereochemistry of reaction at prochirality centers is a powerful method for studying detailed mechanisms in biochemical reactions. As just one example, the conversion of citrate to (ds)-aconitate in the citric acid cycle has been shown to occur with loss of a pro-R hydrogen, implying that the reaction takes place by an anti elimination mechanism. That is, the OH and H groups leave from opposite sides of the molecule. 

A molecule is prochiral if can be converted from achiral to chiral in a single chemical step. A prochiral sp2-hybridized atom has two faces, described as either Re or Si. An sp3-hybridized atom is a prochirality center if, by changing one of its attached atoms, a chirality center results. The atom whose replacement leads to an R chirality center is pro-R, and the atom whose replacement leads to an S chirality center is pro-S. 

Note that the hydroxyl-bearing carbon of citrate is a prochirality center and contains two identical "arms." Because the initial aldol reaction of acetyl CoA to oxaloacetate occurs specifically from the Si face of the ketone carbonyl group, the pro-S arm of citrate is derived from acetyl CoA and the pro-R arm is derived from oxaloacetate. 

Prochirality center (Section 9.13) An atom in a compound that can be converted into a chirality center by changing one of its attached substituents. 

Preeclampsia, Viagra and, 164 Prelog, Vladimir, 181 Prepolymer, epoxy resins and, 673 Priestley, Joseph, 245 Primary alcohol, 600 Primary amine, 916 Primary carbon. 84 Primary hydrogen, 85 Primary structure (protein), 1038 Primer strand (DNA), 1108 pro-R prochiralitv center, 316 pro-S prochirality center, 316 Problems, how to work, 27 Procaine, structure of, 32 Prochirality, 315-317 assignment of, 315-316 naturally occurring molecules and, 316-317... 

Substituted 1-hydroxy cyclohexane-1-carboxyhc acids, which could be prepared from the corresponding cyanohydrins by acid hydrolysis as described above, are important as pharmaceuticals and plant-protective agents. Although the compounds derived from 2- and 3-cyclohexanones have two stereogenic centers, stereoselective syntheses of these interesting products have been published only very recently. " Completely unexpected are the results of HNL-catalyzed additions to 4-substituted cyclohexanones, which do not possess a prochiral center. The (R)-PaHNL-catalyzed addition affords almost exclusively fran -isomers, whereas with (5 )-MeHNL cA-addition is favored (Table 4). ... 

FIGURE 3.1 Formation of a chiral center from a prochiral center. 

The prochirality concept is not necessarily an expression of a precursor-product relationship because there exist stereoselective reactions at pro-chiral elements that do not generate elements of chirality. An illustration of this is the reversible enzymatic dehydration of citric to cu-aconitic acid. In this process two prochiral centers of citric acid disappear and we obtain an achiral line of stereoisomerism that physically coincides with a prochiral plane of prostereoisomerism. 

C2 symmetry is a common feature in chiral bidentate ligands (119). If two identical enantiopure donor groups Y are connected by a tetrahedral bridging atom, any additional group Z at this atom will cause no additional stereo center but a prochiral center (Fig. 18a) (120). (S,S)- and (i2,i )-Trihydroxyglutaric acid are textbook examples for such compounds (120). Inversion of configuration at C3 in (S,S)-trihydroxyglutaric acid (Fig. 18b) yields the identical compound. 

It is worthwhile emphasising that the abovementioned syntheses using chiral auxiliaries covalently bound to the substrate bearing the prochiral center prior to the creation of the new asymmetric centre mean converting the problem of enantiofacial recognition into a problem of diastereofacial selectivity i.e. the pair of enantiomers 41 and 42 are actually obtained from hydrolysis of two different diastereomers 39 and 40. In fact, "direct enantioselectivity" can only be attained by using an external chiral catalyst,23 as shown in Figure 9.1 [26]. 

The two molecules are enantiomers. If two of four groups attached to the C are identical as in CH3CH2CO2H, the 2 H s are enantiotopic and are attached to a prochiral center. Replacement of one of the H s by OH obviously leads to enantiomers. If there is already one chiral center in the molecule, as in (R)-malic acid... 

Another class of ligands for ATH is represented by multidentate Schiff bases and their derivatives. Zassinovich and Mestroni reported on the effective reduction of alkyl aryl ketones catalyzed by a series of lr(l) complexes with chiral bidentate pyridylaldimines, of the form [lr(cod)(NNR )]C104 (76a-f see Scheme 4.31). It was observed that both the activity and selectivity depended heavily on the nature of the subshtuents at the chiral center of the ligand, and also at the prochiral center of the substrate. Optical yields of up to 50% (R-isomer) at 100% conversion were obtained in the ATH of BuC(0)Ph and PhCH2C(0)Ph using [lr(cod)(PPEl)]C104 as the precatalyst (0.1% mol, 83 °C, PrOH, KOH) [66]. 

It should be mentioned that the central carbon atom of citric acid becomes chiral when the two peripheral carboxy groups are substituted differently (examples will be found below). For enzyme reactions it is a prochirality center. This has been shown for vibrioferrin (58) and staphyloferrin B (59). 

Because proteins are made up of L-amino acids, they exhibit chirality in their structures, lacking planes or points of symmetry. Proteins also can exhibit chirality in their interactions with other chiral molecules as well as prochiral centers in other molecules. This latter point is beautifully illustrated by fumarase s catalysis of the dehydration of L-malate, a molecule containing two seemingly equivalent hydrogen atoms ... 

By modification with an optically active compound, RNi can acquire both enantiomer-differentiating ability and diastereoface-differentiating ability in addition to the enantioface-differentiating ability. The diastereoface- and enantiomer-differentiating abilities of MRNi can be observed when a substrate containing both chiral and sp2-prochiral centers is used, because such a compound has a diastereoface and a chirality. 4-Hydroxy-2-pentanone is one of the substrates with a chiral and sp2-prochiral center, as shown in Fig. 17. 

B. Giese, W. Damm, T. Witzel, and H. G. Zeitz, The influence of substituents at prochiral centers on the stereoselectivity of enolate radicals. Tetrahedron Lett. 34 7053 (1993). 

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