Synthetic and Mechanistic Studies of (2 R, 3 S)-3-Vinylmalic Acid as a Mechanism-Based Inhibitor of 3-Isopropylmalate Dehydrogenase

…, T Aoyama, R Suzuki, T Eguchi, T Oshima…

Index: Chiba, Akira; Aoyama, Tetsuya; Suzuki, Rieko; Eguchi, Tadashi; Oshima, Tairo; Kakinuma, Katsumi Journal of Organic Chemistry, 1999 , vol. 64, # 17 p. 6159 - 6165

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Citation Number: 6

Abstract

(2 R, 3 S)-3-Vinylmalic acid (VM) was designed as a mechanism-based inhibitor of threo-3- isopropylmalate dehydrogenase (IPMDH), the rate-determining enzyme responsible for the penultimate step in the biosynthetic pathway of the essential amino acid l-leucine. The synthesis of VM was achieved in six steps from diethyl (R)-malate. Besides its weak activity as a substrate, VM was shown to be a mechanism-based inhibitor (KI= 1.20 mM) for ...