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. Ghangas, Frederick H. Batzold

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 vivo 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
StatePublished - 1974

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Hypothermia
Fluoroacetates
Enantiomers
Toxicity
Esters
Alcohol Dehydrogenase
Poisons
Lethal Dose 50
Metabolic Networks and Pathways
Metabolism
Tumors
Ethanol
Phosphates
Temperature
L-1-deoxyfluoroglycerol 3-phosphate
Testing
pyrazole
Neoplasms

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis of L-1-deoxyfluoroglycerol and its 3-phosphate ester. Effects of the L and D enantiomers in BDF1 mice. / Fondy, Thomas P; Pero, Richard W.; Karker, Katherine L.; Ghangas, Gurdev S.; Batzold, Frederick H.

In: Journal of Medicinal Chemistry, Vol. 17, No. 7, 1974, p. 697-702.

Research output: Contribution to journalArticle

Fondy, Thomas P ; Pero, Richard W. ; Karker, Katherine L. ; Ghangas, Gurdev S. ; Batzold, Frederick H. / Synthesis of L-1-deoxyfluoroglycerol and its 3-phosphate ester. Effects of the L and D enantiomers in BDF1 mice. In: Journal of Medicinal Chemistry. 1974 ; Vol. 17, No. 7. pp. 697-702.
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