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.