Synthesis and characterization of cis- and trans-2,3-epoxybutane-1,4-diol 1,4-bisphosphate, potential affinity labels for enzymes that bind sugar bisphosphates

Abstract

cis- and trans-2,3-Epoxybutane-1,4-diol 1,4-bisphosphate, which can be considered reactive analogs of several sugar bisphosphates, have been synthesized in a continuing effort to develop new and diverse affinity labeling reagents for enzymes which bind phosphorylated substrates. cis-2,3-Epoxybutane-1,4-diol was obtained by epoxidation of commercially available cis-2-butene-1,4-diol with m-chloroperbenzoic acid; the trans epoxide was obtained by reduction of 2-butyne-1,4-diol with LiAlH 4 followed by epoxidation with m-chloroperbenzoic acid. The diols were phosphorylated with diphenyl chlorophosphate, and the phenyl blocking groups were then removed by Pt-catalyzed hydrogenation. By the criterion of their reaction with the sulfhydryl group of glutathione, the phosphorylated epoxides are 6000 times less electrophilic than the previously described and structurally similar reagent 3-bromo-1,4-dihydroxy-2-butanone 1,4-bisphosphate.