Enzymes in organic synthesis. Expedient enantioselective synthesis of (S)‐(−)‐3,4‐dihydroxybutylphosphonate, an isosteric substrate mimic for glycerol phosphate oxidase

The title compound (S)‐(−)‐2 was obtained in enantiomerically pure form and 47% overall yield starting from (S)‐malic acid (S)‐7 by a 5‐step sequence involving reduction to (S)‐1,2,4‐butanetriol (S)‐8, acetalization, and introduction of the phosphonate group by an Arbusow reaction. Compound (S)‐(−)‐2 is a substrate for the L‐glycerol 3‐phosphate oxidase from Pediococcus sp. which quantitatively converts it into 4‐hydroxy‐3‐oxobutylphosphonate 4, an isosteric analog of dihydroxyacetone phosphate. Kinetic constants of the latter reaction were determined.