Synthesis of tritium-labeled azaline B acetate

Reaction of azaline B acetate (1) with freshly prepared trifluoroacetyl hypoiodite in trifluoroacetic acid - methylene chloride solution under anhydrous conditions produced a complex mixture of products from which compounds 2 and 3, resulting from iodination at the 1'- and 8'-positions of the Ac-D Nal1 residue, were isolated by preparative reversed-phase HPLC chromatography. Mass spectral analysis and 1H, 2D DQF-COSY and homonuclear 2D J-resolved NMR experiments confirmed these structures. Reductive tritiation of 2 over 10% Pd/C in EtOH - DMF (1:9, v/v) with 50 Ci T2 followed by chromatographic purification and salt exchange gave 37.5 mCi of tiritated azaline B acetate (4) having > 98% chemical and radiochemical purities and a specific radioactivity of 11.2 Ci/mmol. A single peak at 7.59 pprn was observed in the proton decoupled tritium NMR spectrum. (author)