Prochiral compounds

A large number of biological reactions involve prochiral compounds. One of the steps in the citric acid cycle by which food is metabolized, for instance, is... 

If kinetic resolution is being studied, the ratio of pseudo-e nantiomers can be measured by MS, allowing for the determination of ee-values (and/or of selectivity factors E). The same applies to the reaction of pseudo prochiral compounds. This system has been used successfully in the directed evolution of enantioselective enzymes. However, it should work equally well in the case of asymmetric transition metal catalyzed reactions. In the original version about 1,000 ee-deter-minations were possible per day (Figure 6).94 The second-generation version based on an 8-channel multiplexed spray system enables about 10,000 samples to be handled per day, the sensitivity being 2% ee.96... 

A different MS-based ee-assay makes use of a proline-derived mass-tagged acylating agent.95 In the course of derivatization it is necessary that some degree of kinetic resolution comes about. The sensitivity of the method was reported to be 10% ee. It can also be applied to the reaction of a prochiral compound lacking enantiotopic groups, as in the transformation of acetophenone to phenylethanol. 

Very recently (51), nonequivalence has been found in a variety of additional monobasic solutes whose configurational analysis was thought earlier to lie outside the scope of the CSA technique. 2-Butanol, for example, when dissolved in benzene saturated with TFAE, shows nonequivalence in both methyl resonances. A variety of other chiral and prochiral compounds such as 2-propanol, methyl 2-propyl sulfide, 2-aminobutane, and 2-methyl-1-butanol show nonequivalence for their enantiotopic methyl groups under these conditions. The magnitudes of nonequivalence in these instances are small (0.02-0.03 ppm) but, as illustrated in Figure 4 for enriched 2-butanol,... 

CPDMO is a new bioreagent for the synthesis of optically pure lactones with excellent enantioselectivity. CPDMO is not only effective in desymmetrization of meso and prochiral compounds (Procedure 2, Section 11.8.2), but excellent in carrying out the kinetic resolution of racemates (Procedure 3, Section 11.8.3). Additional examples of optically pure lactones that can be obtained are summarized in Table 11.4. In the fermenter work (Procedure 4, Section 11.8.4), (R)-2-methyl cyclohexanone was not converted, but evaporated under aeration condition (1 wm). This led to the expected product (5)-7-methyl oxepanone at the end of the experiment. The optically pure lactone could be recovered without sdica-gel chromatography separation. However, the production yield may be improved by using a better condenser. 

Reetz and coworkers developed a highly efficient method for screening of enantioselectivity of asymmetrically catalyzed reactions of chiral or prochiral substrates using ESI-MS [60]. This method is based on the use of isotopically labeled substrates in the form of pseudo-enantiomers or pseudo-prochiral compounds. Pseudo-enantiomers are chiral compounds which are characterized by different absolute configurations and one of them is isotopically labeled. With these labeled compounds two different stereochemical processes are possible. The first is a kinetic separation of a racemic mixture, the second the asymmetric conversion of prochiral substrates with enantiotopic groups. The conversion can be monitored by measuring the relative amounts of substrates or products by electrospray mass spectrometry. Since only small amounts of sample are required for this method, reactions are easily carried out in microtiter plates. The combination of MS and the use of pseudo-enantiomers can be used for the investigation of different kinds of asymmetric conversion as shown in Fig. 3 [60]. 

Does a raeio-compound have stereocentra What about a prochiral compound ... 

Asymmetric synthesis starts with a prochiral compound. This is a compound which is not chiral, but can be converted into a chiral compound by a chiral (bio) catalyst. Subsequently, two types of prochiral compounds can be distinguished The first one has a stereoheterotopic face (which usually is a double bond) to which an addition reaction takes place. An example is the conversion of the prochiral compound propene into 1,2-epoxypropane (which has two enantiomers, of which one may be preferentially formed using an enantioselective catalyst). The second type of prochiral compound has two so-called enantiotopic atoms or groups. If one of these is converted, the compound becomes chiral. Meso-compounds belong to this class. Figure 10.5 and 10.6 show some examples of the different types of asymmetric catalysis with prochiral compounds. 

Enantioselective catalysis by kinetic resolution does not start with a prochiral compound but with a mixture of two enantiomers. The chiral catalyst should convert one of the substrate enantiomers, leaving the other one pure. When the enantioselectivity of the catalyst is absolute, the remaining substrate as well as the product may reach an enantiomeric excess of 100%. So the remaining substrate as well as the product may be the target compound, but the maximum yield for either one is only 50%. Therefore... 

Kinetics of Asymmetric Synthesis from Prochiral Compounds... 

In this numbering system derivatives of the parent prochiral compound are given the prefix sn-. Thus, glycerol phosphate, used by cells to construct phospholipids, usually bears a phosphate group on the -CH2OH in the pro-R position of glycerol and is therefore su-3-glycerol phosphate. 

The second MS-based approach does not require any derivatization reaction and has in fact been applied several times in the area of directed evolution [20,33-36]. It makes use of deuterium-labeled pseudo enantiomers or pseudo meso compounds. This practical method is restricted to studies involving kinetic resolution of race-mates and desymmetrization of prochiral compounds bearing reactive enantiotopic groups (Figure 9.2) [20]. 

Figure 51. Enantiotopic differentiation of a prochiral compound by chiral Lewis acids.

Asymmetric Induction during Cathodic Reduction of Prochiral Compounds in the Presence of Chiral Cations... 

With the development of the role for prochirality in biology, the need to demonstrate the existence of this phenomenon and to characterize it in precise structural terms became urgent. Along with such developments, chemists were interested in the study of compounds in which isotopic replacement led to chirality which could be expressed as optical activity. In other words, it was necessary to carry out determinations of the configurations of prochiral compounds. 

---