Biological reaction, alcohol carboxylation

Enzymes are large proteins that act as catalysts for biological reactions. A catalyst, as we saw in Section 12.12, is an agent that speeds up the rate of a chemical reaction without itself undergoing change. For example, sulfuric acid catalyzes the reaction of a carboxylic acid with an alcohol to yield an ester (Section 23.14). 

The aldehyde intermediate can be isolated if 1 equivalent of diisobutvl-aluminum hydride (D1BAH) is used as the reducing agent instead of LiAlH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

Lipases are enzymes that catalyze the in vivo hydrolysis of lipids such as triacylglycerols. Lipases are not used in biological systems for ester synthesis, presumably because the large amounts of water present preclude ester formation due to the law of mass action which favors hydrolysis. A different pathway (using the coenzyme A thioester of a carboxylic acid and the enzyme synthase [Blei and Odian, 2000]) is present in biological systems for ester formation. However, lipases do catalyze the in vitro esterification reaction and have been used to synthesize polyesters. The reaction between alcohols and carboxylic acids occurs in organic solvents where the absence of water favors esterification. However, water is a by-product and must be removed efficiently to maximize conversions and molecular weights. 

The hydrocyanation reactions of electrophilic aldehydes, ketones and their corresponding imines gives direct access to synthetic derivatives of several important structures, including a-hydroxy carboxylic acids, / -amino alcohols and a-tertiary and a-quaternary-a-amino acids. The asymmetric hydrocyanation reaction provides access to chiral synthons, which have proven useful for the construction of many structurally complex and biologically active compounds. Catalysis of these reactions is especially attractive with respect to avoiding the cost and relative chemical inefficiency associated with the use of chiral auxiliaries. 

The nitroaldol (Henry) reaction, first described in 1859, is a carbon-carbon bondforming reaction between an aldehyde or ketone and a nitroalkane, leading to a nitroalcohol adduct [29]. The nitroalcohol compounds, synthetically versatile functionalized structural motifs, can be transformed to many important functional groups, such as 1,2-amino alcohols and a-hydroxy carboxylic acids, common in chemical and biological structures [18, 20, 30, 31]. Because of their important structural transformations, new synthetic routes using transition metal catalysis and enzyme-catalyzed reactions have been developed to prepare enantiomerically pure nitroaldol adducts [32-34]. 

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