2-Iminothiolane as a Coupling Reagent for Polyamine Solid-Phase Synthesis

Significance

Solid-phase synthesis of polyamine having N-alkylmaleimide was achieved by use of 2-iminothiolane as a useful coupling reagent. Thus, the resin-supported tris-Aloc-spermine 2 was prepared from alkoxytrityl resin (PS-TR) with tris-Aloc-spermine 1 and deprotected with Pd(Ph₃P)₄ in dichloromethane to give solid-supported spermine 3. The reaction of the resin 3 with 2-iminothiolane 4 followed by treatment with N-ethylmaleimide 5 in tetrahydrofuran-water afforded the resin-supported N-ethylmaleimide 6a. Polyamine 7a was obtained via TFA-mediated cleavage from the resin 6a in 75% yield with 93% purity.