Dihydroxyacetone natural product synthesis

Fructose 1,6-biphosphate aldolase from rabbit muscle in nature reversibly catalyzes the addition of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde 3-phosphate. The tolerance of this DHAP-dependent enzyme towards various aldehyde acceptors made it a versatile tool in the synthesis of monosaccharides and sugar analogs [188], but also of alkaloids [189] and other natural products. For example, the enzyme-mediated aldol reaction of DHAP and an aldehyde is a key step in the total synthesis of the microbial elicitor (—)-syringolide 2 (Fig. 35a) [190]. 

Ethynyl groups attached to various skeletons were generally oxidized to the hydroxyacetyl functionality. The reaction was useful in the synthesis of natural products and analogues with a dihydroxyacetone side chain, e.g. adriamycin and corticosteroids. Some examples are given in Table 4.1. 

While pyruvate aldolases form only a single stereogenic center, the aldolases specific for dihydroxyacetone phosphate (DHAP, 22) as a nucleophile create two new asymmetric centers at the termini of the new C—C bond. Particularly useful for synthetic applications is the fact that nature has evolved a full set of four stereochemically unique aldolases [27] for the retroaldol cleavage of ketose 1-phosphates 23-26 (Fig. 12). In the direction of synthesis this formally allows the deliberate preparation of any one of the possible four diastereomeric aldol adducts in a building block fashion [15,22,27] by simply choosing the complementary enzyme and starting materials for full control over constitution and absolute configuration of the desired product. 

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