2.11. Bioorganic Example: Aldolase
The aldol reaction is very common in biosynthesis of natural products. For example, the synthesis of fructose (Scheme 2.57) involves an aldol reaction catalyzed by an aldolase (an enzyme that performs aldol reactions).
Scheme 2.57 – General Aldol Reaction and Aldolase-Catalyzed Aldol Reaction for the Synthesis of Fructose.
Enzymes are discussed in greater detail in a subsequent chapter (see Chapter 6). As a brief simplification, enzymes are large and complex polymers made from many amino acids connected in a specific sequence. After the cell synthesizes the polymer(s) that make it up, the enzyme’s chain folds to adopt a very specific shape. In many there is a so-called active site, a place or cavity where the enzyme gathers the reactants and performs the reaction it was generated for.
Enzymes are made from amino acids. Amino acids are discussed in greater detail in a subsequent chapter (see Chapter 4). As a (very) brief simplification, amino acids are molecules that contain a central carbon atom attached to an amine (used in making the polymer chain), a carboxylic acid (used in making the polymer chain), and a so-called side chain. The side chain varies depending on the exact amino acid.
Although the side chains perform many roles in the enzyme, one of their roles is for catalysis; very often one or more side chains point into the active site and are used to catalyze the reaction the enzyme was generated for.
Recall that an enamine, the nitrogen equivalent of an enol, can by formed by amines and aldehydes/ketones (see Section 2.9.4). Aldolase uses the side chains of lysine (which contains an amine) and tyrosine (which can act as a base) to catalyze the aldol reaction and form fructose (Scheme 2.58). These side chains, plus all of the others in the active site, dictate all of the selectivity: regioselectivity, chemoselectivity, and stereoselectivity are all VERY high (>99.999%) because of the extreme control exerted.
Scheme 2.58 – Simplified Aldolase Catalysis Cycle for Fructose Formation.
