Synthesis of modified aldonic acids and studies of their substrate efficiency for dihydroxy acid dehydratase (DHAD)

Article abstract of DOI:10.1071/CH9960349

Modified aldopentonic and aldohexonic acids were synthesized in order to study the electronic requirements for a successful enzymatic conversion into their corresponding 2-keto 3-deoxy analogues by dihydroxy acid dehydratase (DHAD), an enzyme from the biosynthetic pathway of branched chain amino acids. Analytical tests with the novel artificial substrates (18)-(21) and (27) provided evidence that the amount of conversion could be enhanced by replacement of the hydroxy group at C 4 of L-arabinonic acid (21) with less electron-withdrawing, ambivalent or electron-donating substituents. Modified aldohexonic acids were no substrates for DHAD, perhaps due to less perfect binding to the active site presumably for steric reasons. For 4-deoxy-L-threo-pentonic acid (18) the enzymatic conversion into 3,4-dideoxy-2-ketopentonic acid (29) by DHAD could be achieved on a preparative scale.