Short Enzymatic Synthesis of L-Fucose Analogs



A short enzymatic route for the synthesis of L-fucose analogs modified at the nonpolar terminus is reported. In particular, fucose derivatives bearing extended linear (1b) and branched (1e) saturated, or various unsaturated (1c, 1d) aliphatic chains have been prepared, in order to increase hydrophobic contacts. The rather general approach involves a sequential application of the recombinant enzymes L-fuculose 1-phosphate aldolase (FucA) and L-fucose ketol isomerase (FucI) from E.coli. Enantiomerically pure L-fucose analogs have been prepared in up to 30% overall yield starting from the appropriate hydroxyaldehyde precursors and dihydroxyacetone phosphate as readily available components. Unsaturated 2-hydroxyaldehydes have been efficiently prepared by alk(en/yn)yl Grignard addition to cinnamaldehyde followed by controlled ozonolysis of the styrene fragment.