
%0 Journal Article
%A Francis, C. L. 
%A Yang, Q. 
%A Hart, N. K. 
%A Widmer, F. 
%A Manthey, M. K. 
%A He-Williams, H. M. 
%T Total Synthesis of Methotrexate-&#947;-TRIS-Fatty Acid Conjugates
%J Australian Journal of Chemistry
%D 2002/11/12
%V 55
%N 10
%P 635-645
%K 
%R https://doi.org/10.1071/CH02125
%U https://www.publish.csiro.au/paper/CH02125 
%X 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. 
