Abstract
The synthesis of the antifolate 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF) has been modified. It is prepared from 2-acetamido-6-formyl-4(3H)-pyrido[2,3-b]pyrimidone and [P-(N-[1,3-bis(ethoxycarbonyl)propan-1-yl]aminocarbonyl)]phenylmethyl]-triphenylphosphonium bromide. The synthesis proceeds via a sodium hydride promoted Wittig condensation in 1-methyl-2-pyrrolidone followed by catalytic reduction, mild base hydrolysis, and acid precipitation of the product. Synthesis of DDATHF is achieved in a total of seven steps from commercially available reagents. DDATHF is transported effectively into CCRF-CEM cells and inhibits growth of both human (CEM) and murine (L1210) cells in culture. Studies reported here support the view that methotrexate and DDATHF are transported via a shared transport mechanism.
Original language | English (US) |
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Pages (from-to) | 43-49 |
Number of pages | 7 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 265 |
Issue number | 1 |
DOIs | |
State | Published - Aug 15 1988 |
Externally published | Yes |
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology