Fuculose isomerase

Scheme 5.14. Glucose isomerase (GI) and fuculose isomerase (Fuc I) are used in the preparation of aldoses from ketoses.

Combination of FucA and fuculose isomerase for the synthesis of interesting L-fucose analogs having tails with increased hydrophobicity and reactivity (Fessner et al. 2000). Homologues and unsaturated analogs of L-lactaldehyde were well tolerated by FucA with high diasteromeric excess (> 95%). 

L-Fucose isomerase catalyzes the interconversion of L-fucose to L-fuculose and o-arabinose to D-ribulose. It has neither sequence nor structural similarity with the other aldose-ketose isomerases. A crystal structure of the E. coli enzyme with an L-fucitol bound in the active site shows that the active site is located in a 20 A deep pocket, at the bottom of which is a single Mn ion. Mn is bound to Oi and O2 of L-fucitol the side chains of a monodentate Glu-337, a bidentate Asp-361 (with long bonds to both oxygens), His-528 and a water molecule. ... 

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). 

Short syntheses of L-fucose analogues have been achieved (3 enzymatic steps) by aldol condensation of DHAP with various a-hydroxyaldehyde derivatives (using L-fuculose phosphate aldolase), followed by phosphate hydrolysis (alkaline phosphatase) and subsequent ketol isomerization (L-fucose isomerase). Selective C-labelling of thymidine in all positions of the 2 -deoxyribose ring has been achieved using an aldolase-catalysed reaction with appropriately C-labelled DHAP/acetaldehyde substrates. The labelled sugar was then converted... 

In 1952, for the first time, an enzyme that had the ability to isomerise an unsubstituted free sugar, namely o-erythrose into o-g/ycero-tetrulose, was discovered [7]. Subsequently, it was found that Escherichia coli produces enzymatic activity that converts D-arabinose (13) into o-erythro-pentulose (14) and it was suggested that D-arabinose isomerase (EC 5.3.1.3) catalyses the isomerisation of L-fucose (15) into L-fuculose (6-deoxy-L-/yxo-hexulose, 16) (Scheme 4) [8]. 

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). 

Reagents i, Fucose isomerase ii, rtiamnulokinase, ATP iii, DHAP, fuculose 1-phosphate aldolase Scheme 4... 

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