Electrophilic acceptor

Active Figure 23.1 MECHANISM The general mechanism of a carbonyl condensation reaction. One partner becomes a nucleophilic donor and adds to the second partner as an electrophilic acceptor. 

The situation can be summarized by saying that a mixed aldol reaction leads to a mixture of products unless one of the partners either has no a hydrogens but is a good electrophilic acceptor (such as benzaldehyde) or is an unusually acidic nucleophilic donor (such as ethyl acetoacetate). 

The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones (Section 23.5). Mixed Claisen reactions are successful only when one of the two ester components has no a hydrogens and thus can t form an enolate ion. For example, ethyl benzoate and ethyl formate can t form enolate ions and thus can t serve as donors. They can, however, act as the electrophilic acceptor components in reactions with other ester anions to give mixed /3-keto ester products. 

The Michael reaction occurs with a variety of a,/3-unsaturated carbonyl compounds, not just conjugated ketones. Unsaturated aldehydes, esters, thio-esters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions (Table 23.1). Similarly, a variety of different donors can be used, including /3-diketones, /3-keto esters, malonic esters, /3-keto nitriles, and nitro compounds. 

How might the following compounds be prepared using Michael reactions Show the nucleophilic donor and the electrophilic acceptor in each case. 

Step 5 of Figure 29.5 Condensation The key carbon-carbon bond-forming reaction that builds the fatty-acid chain occurs in step 5. This step is simply a Claisen condensation between acetyl synthase as the electrophilic acceptor and malonyl ACP as the nucleophilic donor. The mechanism of the condensation is thought to involve decarboxylation of malonyl ACP to give an enolate ion, followed by immediate addition of the enolate ion to the carbonyl group of acetyl... 

Typically, lyases are quite specific for the nucleophilic donor component owing to mechanistic requirements. Usually, approach of the aldol acceptor to the enzyme-bound nucleophile occurs stereospedfically following an overall retention mechanism, while the facial differentiation of the aldehyde carbonyl is responsible for the relative stereoselectivity. In this manner, the stereochemistry of the C—C bond formation is completely controlled by the enzymes, in general irrespective of the constitution or configuration of the substrate, which renders the enzymes highly predictable. On the other hand, most of the lyases allow a reasonably broad variation of the electrophilic acceptor component that is usually an aldehyde. This feature... 

This chapter deals with the other group of aldolases that catalyzes the reversible aldol reaction of pyruvate as the nucleophilic donor and a sugar as the electrophilic acceptor. Table 1 lists the main aldolases using pyruvate that have been examined for synthetic... 

The other component (the electrophilic acceptor) undergoes nucleophilic addition. 

Carbonyl c nwo carbonyl paitiwrs and involve a comfitnotMin of nucleophilic additi-on ami a-aubstitution stepa One partner the nucleophilic dortor> is converted into ite enohtto ion luvl undergoea an ageneral mechanism of a ovl bonyl condensation reaction ta shown in Figure 23.1. 

R, = OH, Rj = H, R2 = OH, R4 = CHjOH in Table 3), the enantiomeric compound of the one just reported could be easily prepared. Aldol condensation products were obtained as diastereomeric mixtures from L-sugars, such as L-fucose, L-xylose, L-lyxose, and o-sugars epimeric to o-mannose relative to the 3-position, such as D-allose and o-gulose [46-48]. Table 4 lists the corresponding aldol condensation products isolated as diastereomeric mixtures. Also, 3-deoxy-D-mannose by condensation with pyruvate gave a diastereomeric mixture of 6-deoxy-KDN furanose derivatives [43]. All these results confirm that sialic acid aldolase, similar to other aldolases, exhibits broad specificity toward the electrophilic acceptor on the other hand, only pyruvate was reported acceptable as the donor [10]. But very recently, in contradiction to that, 3-fluoro-Neu5Ac and 3-fluoro-KDN could be prepared by the sialic acid aldolase-catalyzed condensation of 3-fluoropyruvate and Af-acetylmannosamine or o-mannose (Scheme 5) [47]. 

Nature uses the two-carbon acetate fragment of acetyd CoA as the major building block for synthesis. Acetyl CoA can act not only as an electrophilic acceptor, being attacked by nucleophiles at the carbonyl group, but also as a nucleophilic donor by loss of its acidic a hydrogen. Once formed, the enolate ion of acetyl CoA can add to another carbonyl group in a condensation reaction. For example, citric acid is biosynthesized by nucleophilic addition of acetyl CoA to the ketone carbonyl group of oxaloacetic acid (2-oxob i-tanedioic acid) in a kind of mixed aldol reaction. 

Heterolytic retrosynthetic disconnection of a carbon-carbon bond in a molecule breaks the TM into an acceptor synthon, a carbocation, and a donor synthon, a carbanion. In a formal sense, the reverse reaction — the formation of a C-C bond — then involves the union of an electrophilic acceptor synthon and a nucleophilic donor synthon. Tables 1.1 and 1.2 show some important acceptor and donor synthons and their synthetic equivalents. "... 

Carbonyl condensation reactions take place between two carbonyl partners and involve a combination of nucleophilic addition and a-substitution steps. One partner fthe nucleophilic donor) is converted into its enolate ion and undergoes an a-substitution reaction when it adds as a nucleophile to thy second partner (the electrophilic acceptor). The general mechanism of a eol bonyl condensation reaction is shown in F ure 23.1. 

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