EPSP synthase inhibitor deisgn III. Synthesis & evaluation of a new 5-oxamic acid analog of EPSP which incorporates a malonate ether as a 3-phosphate mimic

The unusual shikimate oxamic acid analog 3, containing a 3-malonate ether, was synthesized and found to be a potent product-analog inhibitor of EPSP synthase (K(i) = 5.2 +/- 0.2 muM). The potency of 3 confirms that these 3-malonate ethers function as effective 3-phosphate replacements in this system and that the oxamic acid moiety represents an unusual mimetic of the EPSP carboxyvinyl ether group.