VANOXONIN, A NEW INHIBITOR OF THYMIDYLATE SYNTHETASE: II. STRUCTURE DETERMINATION AND TOTAL SYNTHESIS

Acid hydrolysis of vanoxonin yielded one mol each of 2, 3-dihydroxybenzoic acid, L-threonine, L-Nω-hydroxyornithine. Presence of acetyl group in vanoxonin was suggested by the 1H NMR. Periodate oxidation of vanoxonin liberated one mol of acetic acid suggesting that the acetyl group bound to the ω-nitrogen of Nω-hydroxyornithine. The sequence of three components was determined to be L-N-(2, 3-dihydroxybenzoyl)threonyl-L-(Nω-acetyl-Nω-hydroxy)ornithine by mass spectrometric analysis. This structure was confirmed by the total synthesis of vanoxonin.