Two new irreversible inhibitors of dihydrodipicolinate synthase: diethyl ( E, E)-4-oxo-2,5-heptadienedioate and diethyl ( E)-4-oxo-2-heptenedioate

Abstract

Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and an important antibiotic target. The enzyme catalyses the condensation of ( S)-aspartate semialdehyde (ASA) and pyruvate to form dihydrodipicolinate. Two new irreversible inhibitors of dihydrodipicolinate synthase are reported, designed to mimic the acyclic enzyme-bound condensation product of ASA and pyruvate. These compounds represent an important new lead in the design of potent inhibitors for this enzyme.