DHAP aldolase racemate resolution

Figure 10.17 Kinetic enantiopreference of class II DHAP aldolases useful for racemic resolution of a-hydroxyaldehydes.

Figure 17 Racemate resolution by class II DHAP aldolases due to their kinetic enantioselectivity for L-configurated a-hydroxyaldehyde substrates [110,111].

The aldehyde substrates may be used as racemic mixtures in many cases, as the aldolase catalyzed reactions can concomitantly accomplish kinetic resolution. For example, when DHAP was combined with d- and L-glyceraldehyde in the presence of FDP aldolase, the reaction proceeded 20 times faster with the D-enantiomer. Fuc 1-P aldolase and Rha 1-P aldolase show kinetic preferences (greater than 19/1) for the L-enantiomer of 2-hydroxy-aldehydes. Alternatively, these reactions may be allowed to equilibrate to the more thermodynamically favored products. This thermodynamic approach is particularly useful when the aldol products can cyclize to the pyranose form. Since the reaction is reversible under thermodynamic conditions, the product with the fewest 1,3-diaxial interactions will predominate. This was demonstrated in the formation of 5-deoxy-5-methyl-fructose-l-phosphate as a minor product (Scheme 5.5).20a 25 The major product, which is thermodynamically more stable, arises from the kinetically less reaction acceptor. 

Preparation of enantiometrically pure aldehyde substrates for DHAP-dependent aldolase reactions has been accomplished by a combination of enzymatic and chemical methods. The lipase-catalyzed resolution of racemic aldehyde precursors has been accomplished by enantioselective acetate hydrolysis, as exhibited in the preparation of enantiomerically pure R- and S -glycidaldehyde acetals (Scheme 5.10).31 Regioselective ring opening of the epoxides, followed by acetal hydrolysis, generated the aldehydes in enantiomerically pure form. 

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