REVERSIBLE N,O-HALOACYL SHIFT IN SERINE DERIVATIVES WITH ANTITUMOR ACTIVITY

• Published in: Canadian journal of chemistry 1961-12, Vol.39 (12), p.2491-2501
• Main Authors: Levi, I, Weed, J. W. R, Laflamme, G, Koller, A. E
• Format: Article
• Language: English
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v61-329

Large doses of N-dichloroacetyl- DL -serine sodium salt were required to cause regression of Sarcoma-37 in mice. About 56% of the unchanged compound was recovered from the urine. These observations suggest that the antitumor activity may reside in a metabolic product of the N-dichloroacetyl serine. It is postulated that the active compound is the corresponding O-dichloroacetyl- DL -serine formed from the N-acyl compound by an in vivo enzymatically controlled shift which takes place via the hydroxyoxazolidine and (or) the oxazoline rings. O-Dichloroacetyl- DL -serine hydrochloride was prepared by treating a suspension of N-dichloroacetyl- DL -serine in anhydrous ether with gaseous hydrogen chloride. The free base, O-dichloroacetyl- DL -serine, is an extremely labile compound and reverts to the N-compound in neutral aqueous solution at room temperature. The hydrochloride salt, however, is stable, in which form it was isolated and characterized. The same compound was prepared from serine and dichloroacetic anhydride in dichloroacetic acid. O-Dichloroacetyl- DL -serine hydrochloride displays an antitumor effect against Sarcoma-37 and Sarcoma-180 in mice. The work has been extended to the monochloro- and trichloro-acetyl derivatives of serine.