Synthesis of L-1-Deoxyfluoroglycerol and Its 3-Phosphate Ester. Effects of the L and D Enantiomers in BDF1 Mice

Thomas P. Fondy, Richard W. Pero, Katherine L. Karker, Gurdev S. Changas, Frederick H. Batzold

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

L-1-Deoxyfluoroglycerol and L-1-deoxyfluoroglycerol 3-phosphate were synthesized from D-isopropylideneglycerol through D-1-benzyl-3-tosylglycerol and tosyl displacement by KF from D-3-tosyl-1,2-isopropylideneglycerol. The L enantiomers were more toxic than the D by a factor of 2 in BDF1 mice. At one-half their LD50 doses these fluoro organics produced a strong hypothermic effect amounting to 12° within a few hours. Ethanol or pyrazole inhibited the toxicity and hypothermia due to the fluorotriitols but pyrazole did not affect the toxicity or hypothermia due to fluoroacetate, indicating that alcohol dehydrogenase functions in the conversion of the fluorotriitols to fluoroacetate. Toxicities of the fluoro organics were greatly enhanced when hypothermia was prevented by maintaining the ambient temperature at 33°. In the presence of pyrazole the toxicity at 33° was reduced by a factor of 10. The application of hypothermia in the study of the in uiuo metabolism of fluoro organics and a possible metabolic pathway for conversion of fluorotriitols to fluoroacetate is suggested. These results permit the design of chemotherapeutic protocols for the testing of the 1-deoxyfluoroglycerols and their 3-phosphates in tumor model systems employing BDF1 mice.

Original languageEnglish (US)
Pages (from-to)697-702
Number of pages6
JournalJournal of Medicinal Chemistry
Volume17
Issue number7
DOIs
StatePublished - Jul 1 1974

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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