Aldolase-catalyzed reactions, common

From a synthetic point of view, the chemically catalyzed and the aldolase-catalyzed reactions complement each other. Both can catalyze the synthesis of compounds that are difficult to obtain with the other type of catalyst. Aldolases have an excellent control over the regiochemistry and accept a wide variety of acceptor molecules. As mentioned above they allow only a few donor molecules. The aldolases that are commonly used activate four different donor molecules and are classified according to them (Scheme 5.20) [2-4, 40, 43]. Other aldolases are known, too, but their application for synthesis has so far been very limited and they will therefore not be discussed here. 

There have been more than 20 aldolases isolated, eight of which have been explored for organic synthesis (6). Aldolases possess two interesting common features the enzymes are specific for the donor substrate but flexible for the acceptor component, and the stereochemistry of aldol reaction is controlled by the enzyme not by the substrates. In our previous study, we have described the use of lipases, hexokinases, glycosyl transferases and rabbit muscle aldolase for the synthesis of certain fluorosugars (7). This review describes our recent development in aldolase-catalyzed reactions for the synthesis of fluorosugars. 

Aldolases catalyze asymmetric aldol reactions via either Schiff base formation (type I aldolase) or activation by Zn2+ (type II aldolase) (Figure 1.16). The most common natural donors of aldoalses are dihydroxyacetone phosphate (DHAP), pyruvate/phosphoenolpyruvate (PEP), acetaldehyde and glycine (Figure 1.17) [71], When acetaldehyde is used as the donor, 2-deoxyribose-5-phosphate aldolases (DERAs) are able to catalyze a sequential aldol reaction to form 2,4-didexoyhexoses [72,73]. Aldolases have been used to synthesize a variety of carbohydrates and derivatives, such as azasugars, cyclitols and densely functionalized chiral linear or cyclic molecules [74,75]. 

Pyruvate-dependent aldolases catalyze the breaking of a carbon-carbon bond in nature. This reaction can, however, be reversed if an excess of pyruvate is used, establishing one new stereocenter in the course of it. The natural function of phosphoenolpyruvate (PEP)-dependent aldolases on the other hand is to catalyze the synthesis of a-keto acids. Since PEP is a very reactive, unstable and difficult to prepare substrate, they are not commonly used in synthesis. 

Aldol reactions occur in many biological pathways but are particularly common in carbohydrate metabolism where enzymes called aldolases catalyze the addition of a ketone enolate ion to an aldehyde. Aldolases occur in all organisms and are of two types. Type 1 aldolases occur primarily in animals and higher plants type 11 aldolases occur primarily in fungi and bacteria. Both types catalyze the same kind of reaction, but type 1 aldolases operate through an enamine while type 11 aldolases require a metal ion (usually Zn " ") as Lewis acid and operate through an enolate ion. 

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