Synthesis of Inhibitors of Imidazole Glycerol Phosphate Dehydratase

摘要

With recognition that chemical disruption of the biosynthesis of amino acids can lead to plant death, the enzymes from these pathways have become the target for rational design of inhibitors as potential herbicides. Contrary to an increasing interest in the enzymes of biosynthesis of essential amino acids such as aromatic amino acids and branched-chain amino acids, enzymes of histidine biosynthesis have drawn less attention until recently. Imidazole glycerol phosphate (IGP) dehydratase (EC 4.2.1.19) is an enzyme involved in the histidine biosynthesis pathway. It catalyzes the conversion of D-erythro-(2R,3S)-imidazole glycerol phosphate (IGP) to imidazole acetol phosphate (IAP) (Scheme 1). This is a unique dehydration reaction characterized by the unusual mechanistic feature that the substrate requires no inline or carbonyl group a to the departing hydrogen. Since IGP dehydratase plays a key role in the biosynthesis of an essential amino acid, it is of interest to examine its inhibitors as potential herbicides. We now disclose the design and synthesis of inhibitors based on a plant IGP dehydratase isolated from wheat germ. During the course of our studies, Cox and his co-workers have reported a closely related work using recombinant yeast IGP dehydratase expressed in Escherichia coli.