
TY  - JOUR
A1  - Francis, C. L. 
A1  - Yang, Q. 
A1  - Hart, N. K. 
A1  - Widmer, F. 
A1  - Manthey, M. K. 
A1  - He-Williams, H. M. 
T1  - Total Synthesis of Methotrexate-&#947;-TRIS-Fatty Acid Conjugates
JF  - Australian Journal of Chemistry
JO  - Aust. J. Chem.
Y1  - 2002
VL  - 55
IS  - 10
SP  - 635
EP  - 645
KW  - 
UR  - https://doi.org/10.1071/CH02125 
N2  - Several routes for the regiospecific synthesis of lipophilic &#947;-conjugates of methotrexate are described. Coupling of methotrexate-&#945;-tert-butyl ester with glycyl-TRIS-(mono-/di-/tri-)palmitate followed by trifluoroacetic acid cleavage of the &#945;-protection afforded the target methotrexate-&#947;-glycyl-TRIS-(mono-/di-/tri-)palmitate derivatives. Methotrexate-&#945;-benzyl-&#947;-glycyl-TRIS-tripalmitate was prepared but no method was found to selectively cleave the &#945;-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-&#947;-glycyl-TRIS-palmitate derivatives efficiently afforded the desired conjugates. 
ER  -

