Radiosynthesis of antitumor spliceosome modulators

A set of novel antitumor agents (the sudemycins) has recently been described that are analogs of the natural product FR901464. We report the radiosynthesis of two of these antitumor drug lead compounds, using a three step procedure: (1) ester hydrolysis, (2) Lindlar's catalyst/tritium gas to give a ( S,Z)-4-acetoxypent-2-enoic acid derivative, and finally (3) amide bond formation. These labeled analogs are useful in developing a better understanding of the pharmacological properties of this new class of therapeutic lead compounds. ► The radiosynthesis of two antitumor drug lead compounds; analogs of FR901464. ► Tritium incorporation via reduction of a (S)-4-acetoxypent-2-ynoic acid derivative. ► The amidation of (S,Z)-4-acetoxypent-2-enoic acid derivative to obtain analogs. ► These analogs are important tools for biochemical and pharmacology experiments.