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 language | English (US) |
|---|---|
| Pages (from-to) | 697-702 |
| Number of pages | 6 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 17 |
| Issue number | 7 |
| State | Published - 1974 |
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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 journal › Article
}
TY - JOUR
T1 - Synthesis of L-1-deoxyfluoroglycerol and its 3-phosphate ester. Effects of the L and D enantiomers in BDF1 mice
AU - Fondy, Thomas P
AU - Pero, Richard W.
AU - Karker, Katherine L.
AU - Ghangas, Gurdev S.
AU - Batzold, Frederick H.
PY - 1974
Y1 - 1974
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0016224085&partnerID=8YFLogxK
M3 - Article
C2 - 4836399
AN - SCOPUS:0016224085
VL - 17
SP - 697
EP - 702
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 7
ER -