L-Fuculose 1-phosphate aldolase

W. D. Fessner, G. Sinerius, A. Schneider, M. Dreyer, G. E. Schulz, J. Badia, and J. Arguilar, Diastereoselective enzymatic aldol additions L-Rhamnulose and L-fuculose 1-phosphate aldolases from E. coli, Angew. Chem, lnt. Ed. Engl. 30 555 (1991). 

Table 5. Substrate tolerance of L-rhamnulose 1-phosphate and L-fuculose 1-phosphate aldolases [195,347]...

Water-in-oil gel emulsions were tested in enzymatic aldolization of selected N-Cbz-amino aldehydes (Figure 19.3), N-Cbz-3-amino propanal (4), N-Cbz-glycinal, (5), (S)-N-Cbz-alaninal (6), and (R)-N-Cbz-alaninal (7) catalyzed by RAMA and L-rham-nulose-1-phosphate aldolase (RhuA) and L-fuculose-1-phosphate aldolase (FucA) from Escherichia coU [27,28]. The largest differences between conventional dimethyl formamide (DMF)/water co-solvent systems and gel emulsions were observed with RAMA and FucA catalysts (Figure 19.3). The emulsion media enhanced the catalytic efficiency of RAMA towards the N-Cbz amino aldehydes tested three, five. 

Figure 13-7 Interaction of the bound zinc ion of L-fuculose-1-phosphate aldolase and catalytic side chains with the substrate in the active site of the enzyme as revealed by X-ray crystallography and modeling. See Dreyer and Schulz. ...

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). 

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). 

These systems were tested in the enzymatic aldolization of a variety of A/-Cbz-aminoaldehydes catalyzed by D-fructose-l,6-bisphosphate aldolase from rabbit muscle (RAMA) and L-rhamnulose-1-phosphate aldolase and L-fuculose-1-phosphate aldolase from E. coli (Espelt et al. 2003 a,b, 2005). The largest differences between conventional DMF/water cosolvent systems and gel emulsions were observed with RAMA catalyst (Fig. 6.5.11). 

In context with a project aimed at structure-activity relationships of sialyl Lewis X epitope analogues, a range of new L-fucose derivatives with increased hydrophobicities of the C-5 substituents, such as compounds 124 and 126, was recently synthesised [100] employing Fessner s proven L-fuculose 1-phosphate aldolase/L-fucose isomerase protocol (Scheme 38). 

Aldol addition of DHAP to aldehydes is catalyzed by DHAP-dependent aldolases. Two stereogenic centers are formed and therefore four possible stereoisomers can be obtained. Although nature has evolved a set of four distinct stereocomplementary types (Scheme 10.3), so far, only three of the known DHAP-dependent aldolases, namely the D-fructose-l,6-bisphosphate aldolase (FruA), L-rhamnulose-1-phosphate aldolase (RhuA), and L-fuculose-1-phosphate aldolase (FucA), have found broad synthetic applicability due to their high stereoselectivity and broad acceptor tolerance [5,77]. DHAP-dependent aldolases are highly selective for the nucleophilic substrate DHAP, tolerating only few isosteric modifications [84-88]. 

Stereocomplemenlary set of DHAP-dependent aldolases. D-Fructose-1,6-bisphosphate aldolase (FruA), L-rhamnulose-1-phosphate aldolase (RhuA), L-fuculose-1-phosphate aldolase (FucA), D-tagatose-1,6-hisphosphate aldolase (TagA)... 

Espelt, L., Bujons, J., Parella, T., Calveras, J., Joglar, J., Delgado, A., and Clap, R, Aldol additions of dlhydroxyacetone phosphate to N-Cbz-amino aldehydes catalyzed by L-fuculose-1-phosphate aldolase in emulsion systems Inversion of stereoselectivity as a function of the acceptor aldehyde. Chem. Eur. J. 2005,11 (5), 1392-1401. 

Joerger, A. C., Mueller-EHeckmann, C., and Schulz, G. E., Structures of L-fuculose-1-phosphate aldolase mutants outlining motions during catalysis. /. Mol. Biol. 2000,303 (4), 531-543. 

Table 5 Substrate Tolerance of L-Rhamnulose 1-Phosphate and L-Fuculose 1-Phosphate Aldolases [97,111]...

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