Enzymes in organic synthesis, 15 - Short enzymatic synthesis of L-fucose analogs

A short enzymatic route for the synthesis of L-fucose analogs modified at t he nonpolar terminus is reported. In particular, fucose derivatives bearing extended Linear (Ib) and branched (1e) saturated, or various unsaturated ( Ic, Id) aliphatic chains have been prepared, in order to increase hydrophob ic contacts. The rather general approach involves a sequential application of the recombinant enzymes L-fuculose l-phosphate aldolase (FucA) and L-fuc ose ketol isomerase (FucI) from E, coli. Enantiomerically pure L-fucose ana logs have been prepared in up to 30% overall yield starting from the approp riate 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 co ntrolled ozonolysis of the styrene fragment.