Science of Synthesis

Clapés, P., Science of Synthesis: Biocatalysis in Organic Synthesis, (2015) 2, 33.

DHAP dependent aldolases are highly specific for 1,3-dihydroxyacetone phosphate (‌1‌) as the donor component;[‌10‌] therefore, an economical access to this compound is instrumental for the preparative exploitation of these enzymes. 1,3-Dihydroxyacetone phosphate (‌1‌) is chemically unstable, particularly under alkaline conditions, and decomposes into inorganic phosphate and 2-oxopropanal (methylglyoxal), both of which may inhibit the aldolase. 1,3-Dihydroxyacetone phosphate (‌1‌) can be prepared chemically, enzymatically, or by a combination of both techniques. Detailed descriptions of the different methodologies are available in Science of Synthesis: Stereoselective Synthesis [Stereoselective Reactions of Carbonyl and Imino Groups (Section 2.14)], a review,[‌11‌] and are also mentioned in Section 1.3.3. The chemical (‌Scheme 2‌) and enzymatic methodologies (‌Schemes 3‌–‌6‌), as well as the in situ formation of 1,3-dihydroxyacetone phosphate mimics by reversible ester formation between 1,3-dihydroxyacetone (‌2‌) and arsenate or borate salts (‌Scheme 7‌) are summarized here; the yield of 1,3-dihydroxyacetone phosphate (‌1‌) generated using enzymatic synthesis is unknown, since the synthesis is normally coupled with an ensuing aldol addition reaction. The fact that many methods exist for the synthesis of 1,3-dihydroxyacetone phosphate (‌1‌) indicates that an ideal methodology does not exist. While the various chemical routes suffer from either low yields, complicated workup, or toxic reagents or catalysts, the enzymatic routes often suffer from more complex product mixtures and the need to control the activity of multiple enzymes within one reaction scheme. Although both types of synthetic route require further improvement, particularly for application on an industrial scale, they allow the preparation of complex polyfunctional molecules effectively on the laboratory scale.

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