Dihydroxyacetone phosphate, preparation

Figure 10.18 Enzymatic in situ generation of dihydroxyacetone phosphate from fructose 1,6-bisphosphate (b), with extension to an in vitro artificial metabolism for its preparation from inexpensive sugars alongthe glycolysis cascade (a), and utilization for subsequent stereoselective carbon-carbon bond formation using an aldolase with distinct stereoselectivity (c).

Figure 10.19 Oxidative enzymatic generation of dihydroxyacetone phosphate in situ for stereoselective aldol reactions using DHAP aldolases (a), and extension by pH-controlled, integrated precursor preparation and product liberation (b).

Espelt, L., Parella, T., Bujons, J., Solans, C., Joglar, J., Delgado, A. and, Clapes, P., Stereoselective aldol additions catalyzed hy dihydroxyacetone phosphate-dependent aldolases in emulsion systems preparation and structural characterization of linear and cyclic iminopolyols from aminoaldehydes. Chem. Eur. J., 2003, 9, 4887. 

The original preparation of 6-C-perfluoroalkyl-D-fructose has been reported. The first step of this synthesis is the perfluoroalkylation of acrolein acetal. The key step of the synthesis is an aldol condensation between D-3-fluoroalkylglyceraldehyde and dihydroxyacetone phosphate, with RAMA as biocatalyst (RAMA is an aldolase found in rabbit muscles) (Figure 6.43). ... 

The majority of useful lyase families utilize anionically functionalized substrates such as pyruvate or dihydroxyacetone phosphate which remain unaltered during catalysis. The charged group thereby introduced into the products (phosphate, carboxylate) not only constitutes a handle for binding of the substrates by the enzymes but also can facilitate the preparative isolation from... 

Stable isotope-labelled intermediates playing an important role in the study of the mevalonate as well as the deoxyxylulose phosphate pathway of isoprenoid biosynthesis have been prepared. C- and " C-labelled 4-diphosphacytidyl-2C-methyl-D-erythrytol (52) and 2C-methyl-D-erythrytol-4-phosphate (53) have been obtained in milimol quantity and in high yield by sequences of one-pot reactions using C-labelled pyruvate, or dihydroxyacetone phosphate... 

NaBH4 reduction with the help of CeCl3 -7H20 to obtain threo derivatives 232 (O Scheme 61). An enzymatic route for the synthesis of L-fucose analogs modified at the non-reducing end is reported by Fessner et al. [86], Using 2-Hydroxy-2-methylpropanal 233 and dihydroxyacetone phosphate 234 as substrates, branched fucose derivative 237 has been prepared via recombinant L-fuculose 1-phosphate aldolase (FucA) and L-fucose ketol isomerase (Fuel) in E. coli (O Scheme 62). 

I rcpMicil hy hiMlIn ii mixluic of l.l imilcx ol phosphoiyl chloridu imil 2 inolcs uf phenol lo 180 iind distilling the product. It is used Tor the preparation of dl-glyceraldehyde 3-phosphoric acid, and dihydroxyacetone phosphate," and diphenyl-... 

Fessner et al.[256] developed an efficient method for the synthesis of L-fucose analogs modified at the nonpolar terminus by means of L-fucose isomerase and l-fuculose 1-phosphate aldolase from E. coli. Various L-fucose analogs bearing linear or branched aliphatic side chains were prepared in about 30% overall yield with hydroxyaldehyde precursors and dihydroxyacetone phosphate as the starting materials (Fig. 17-32). 

We have developed preparative enzymatic syntheses of several unusual hexoketoses using fructose-1,6-diphosphate aldolase (FDP-aldolase, E.C.4.1.2.13) as catalyst and dihydroxyacetone phosphate (DHAP) and an aldehyde as substrates (15). The enzyme appears to be very specific for DHAP but will accept a variety of aldehydes as acceptors. The ketose-1-phosphates prepared are converted to the phosphate free ketoses after removal of the phosphate group by acid- or phosphatase-catalyzed hydrolysis. The ketoses can be isomerized stereospecifically to aldoses catalyzed by glucose isomerase (E.C.5.3.1.5.) from Flavobacteriuum arborescens. The equilibrium mixtures of aldoses and ketoses are then separated by chromatography on Dowex 50 (Ba ) or Dowex 1 (HSO "). Figure 1 illustrates the preparation of a mixture of 6-deoxy-6-fluoro-D-fructose... 

Dihydroxyacetone phosphate-dependent aldolases (DHAP-aldolases) have been used widely for preparative synthesis of monosaccharides and sugar analogs (Fessner and Walter 1997 Wymer and Toone 2000 Silvestri et al. 2003). Among them, RAMA RhuA and FucA from E. coli are the most available aldolases, especially the former which was one of the first to be commercialized (Fessner and Walter 1997 Takayama et al. 1997). In many of the chemo-enzymatic strategies they are involved, the biocatalytic aldol addition to the configuration of the newly stereogenic centers is fixed by the enzyme. However, pertinent examples have been reported in which... 

A comprehensive review (260 refs.) on the synthesis of carbohydrates from noncarbohydrate sources covers the use of benzene-derived diols and products of Sharpless asymmetric oxidation as starting materials, Dodoni s thiazole and Vogel s naked sugar approaches, as well as the application of enzyme-catalysed aldol condensations. The preparation of monosaccharides by enzyme-catalysed aldol condensations is also discussed in a review on recent advances in the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics, in parts of reviews on the formation of carbon-carbon bonds by enzymic asymmetric synthesis and on carbohydrate-mediated biochemical recognition processes as potential targets for drug development, as well as in connection with the introduction of three Aldol Reaction Kits that provide dihydroxyacetone phosphate-dependent aldolases (27 refs.). A further review deals with the synthesis of carbohydrates by application of the nitrile oxide 1,3-dipolar cycloaddition (13 refs.). ... 

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