Regioselective synthesis of peptidic derivatives and glycolamidic esters of Methotrexate

Convenient methods for regioselective syntheses of Methotrexate peptidic conjugates are described. Solid phase synthesis for derivatives of Methotrexate containing an amide bond has been applied and showed higher efficiency than liquid phase synthesis. Synthetic pathways for regioselective preparation of Glycolamidic ester derivatives of Methotrexate were also developed using 4-amino-4-deoxy-N10-methylpteroic acid as starting material. These ester bonds were obtained either in solution or by using a combined liquid and solid phase synthesis.