Preparation of (±)-(erythro)-and (±)-(threo)-2-vinyl citric acids as potential mechanism-based inhibitors of ATP-citrate lyase

Article abstract of DOI:10.1016/0040-4039(91)80046-9

The dianion of diethyl-1,3-acetone dicarboxylate 6 was reacted with a vinyl cation equivalent, 2-bromoethyl phenyl selenide, to give the mono alkylated 3-oxoglutarate 7 in 80% yield. Subsequent four-step elaboration gave the title citric acid analogues. These agents were designed as potential mechanism-based inhibitors of ATP-citrate lyase, an enzyme involved in cholesterol and lipid biosynthesis.