Chemoenzymatic synthesis of 4-diphosphocytidyl-2-C-methyl-d-erythritol: a substrate for IspE

Enantiomerically pure 2-C-methyl-d-erythritol 4-phosphate 1 (MEP) is synthesized from 1,2-O-isopropylidene-α-d-xylofuranose via facile benzylation in good yield. Subsequently, 1 is used for enzymatic synthesis of 4-diphosphocytidyl-2-C-methyl-d-erythritol 2 (CDP-ME) using 4-diphosphocytidyl-2-C-methyl-d-erythritol synthase (IspD). The chemoenzymatically synthesized 2 can be used as substrate for assay of IspE and for high throughput screening to identify IspE inhibitors.