Solid-phase synthesis of polyamine spider toxins and correlation with the natural products by HPLC-MS/MS

A recently developed new and divergent approach for the solid-phase synthesis of polyamines and polyamine derivatives was extended to the preparation of linear pentamines, and it was applied to the synthesis of three quartets of isomeric polyamine spider toxins. The twelve synthetic acylpolyamines were investigated by HPLC-UV(DAD)-MS and HPLC-UV(DAD)-MS/MS and compared with the natural products in the complex mixture of the venom of Agelenopsis aperta. The comparative investigation supported the structures and assignments of seven previously found toxins and allowed the identification of an additional five polyamine derivatives in the natural sample. The MS/MS study of the isomerically pure polyamine derivatives revealed furthermore a characteristic pattern for the fragmentation of these compounds, which can possibly be used as evidence in the trace analysis of other polyamine derivatives.