Synthesis of the 7-hydroxy metabolites of methotrexate and 10-ethyl-10-deazaaminopterin.
The potent folate antagonists methotrexate and 10-ethyl-10-deazaaminopterin are oxidized in vivo to their 7-hydroxy derivatives. A specific cyanation at the C-7 position of the pteridine ring system using diethyl phosphorocyanidate converted the dimethyl esters of methotrexate and 10-ethyl-10-deazaaminopterin to the corresponding 7-cyano dimethyl ester derivatives, which were hydrolyzed to the 7-hydroxy metabolites.
Dawson
M I
MI
Bio-Organic Chemistry Laboratory, SRI International, Menlo Park, CA 94025, USA.
O'Krongly
D
D
Hobbs
P D
PD
Barrueco
J R
JR
Sirotnak
F M
FM
D000630:Aminopterin / Q000031:analogs & derivatives* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000378:metabolism*; D008727:Methotrexate / Q000378:metabolism*; D010084:Oxidation-Reduction
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; C040210:edatrexate; D000630:Aminopterin; D008727:Methotrexate