| Autor: |
Qi Yang, Noel K. Hart, Michael K. Manthey, H. Ming He‐Williams, Fred Widmer, Craig L. Francis |
| Rok vydání: |
2002 |
| Předmět: |
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| Zdroj: |
Australian Journal of Chemistry. 55:635 |
| ISSN: |
0004-9425 |
| DOI: |
10.1071/ch02125 |
| Popis: |
Several routes for the regiospecific synthesis of lipophilic γ-conjugates of methotrexate are described. Coupling of methotrexate-α-tert-butyl ester with glycyl-TRIS-(mono-/di-/tri-)palmitate followed by trifluoroacetic acid cleavage of the α-protection afforded the target methotrexate-γ-glycyl-TRIS-(mono-/di-/tri-)palmitate derivatives. Methotrexate-α-benzyl-γ-glycyl-TRIS-tripalmitate was prepared but no method was found to selectively cleave the α-ester. A method where the diaminopteridinylmethyl moiety was attached last was successful, but was low yielding in the final step. Coupling of 4-amino-4-deoxy-N10-methylpteroic acid with glutamoyl-γ-glycyl-TRIS-palmitate derivatives efficiently afforded the desired conjugates. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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