PREPARATION OF [2',3',5',6'-H-2(4)]PTEROYLGLUTAMIC ACID

Folic acid plays a key role in nucleic acid biosynthesis, essential fo r normal cell proliferation and function. Localized folate deficiencie s may be related to changes in cytology associated with cancer develop ment; analogs of folic acid, such as methotrexate, are potent chemothe rapeutic agents and are widely used either alone or in combination the rapy for many types of cancer, In this report we describe the synthesi s of a tetra-deuterated folic acid from perdeuterated toluene. The pri mary intermediate, N-(4-amino [2,3,5,6-H-2(4)]benzoyl)-L-glutamic acid diethyl ester was coupled to N(2')-acetyl-6-formylpterin to create [2 ',3',5',6'-H-2(4)]folic acid. A similar scheme can be used for the pre paration of [1',2',3',4',5',6'-C-13(6)]folic acid from [C-13(6)] ring labeled toluene.