Chemical and enzymatic routes to dihydroxyacetone phosphate

Abstract

Stereoselective carbon-carbon bond formation with aldolases has become an indispensable tool in preparative synthetic chemistry. In particular, the dihydroxyacetone phosphate (DHAP)-dependent aldolases are attractive because four different types are available that allow access to a complete set of diastereomers of vicinal diols from achiral aldehyde acceptors and the DHAP donor substrate. While the substrate specificity for the acceptor is rather relaxed, these enzymes show only very limited tolerance for substituting the donor. Therefore, access to DHAP is instrumental for the preparative exploitation of these enzymes, and several routes for its synthesis have become available. DHAP is unstable, so chemical synthetic routes have concentrated on producing a storable precursor that can easily be converted to DHAP immediately before its use. Enzymatic routes have concentrated on integrating the DHAP formation with upstream or downstream catalytic steps, leading to multi-enzyme arrangements with up to seven enzymes operating simultaneously. While the various chemical routes suffer from either low yields, complicated work-up, or toxic reagents or catalysts, the enzymatic routes suffer from complex product mixtures and the need to assemble multiple enzymes into one reaction scheme. Both types of routes will require further improvement to serve as a basis for a scalable route to DHAP.

Biosynthesis of l -Sorbose and l -Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain

“…Although L-sorbose/L-psicose could be synthesized from DHAP and L-glyceraldehyde via the one-pot reaction system, compound DHAP, which is unstable and currently very expensive, limited its application for large-scale production of Lpsicose. Several enzymatic approaches from glycerol or dihydroxyacetone have been developed to synthesize DHAP; however, the yield has not advanced beyond small scale (25). The substance DHAP is also a natural intermediate of the glycolytic pathway, which indicates that DHAP can be obtained from glucose through the glycolytic pathway.…”

Enzyme‐Catalyzed Aldol Additions

“…Furthermore, if the phosphate group must be removed from the final product, the use of DHAP reduces significantly the atom economy of the process. DHAP can be prepared chemically or enzymatically or by a combination of both techniques [19,79]. Chemical strategies described for the DHAP preparation often suffer from either low yields, complicated work-up, or toxic reagents or catalysts.…”

Enzymes Catalyzing CC Bond Formation for the Synthesis of Monosaccharide Analogs

“…Many strategies for obtaining sugars and analogs using an FruA -catalyzed reaction for stereochemical control have been described [1 -5] . For synthetic applications, DHAP is required and various strategies have been reported [6] , together with our own procedures [7b, 8 -10] . Transketolase in vivo is the key enzyme in the non -oxidative pentose phosphate pathway.…”

“…The DHAP preparations by chemical and enzymatic routes have been recently reviewed by Sch ü mperli et al . [6] .…”