Syntheses of [13C,15N]-labeled polyamines

[1,4-C-13(2),1,4-N-15(2)]butanediamine (1), a key compound in the syntheses of [5,8-C-13(2),1,4,8-N-15(3)]spermidine (2) and [5,8-C-13(2),1,4,8,12-N-15(4)]spermine (3), has been prepared as part of a 6-step process from 1,2-dibromoethane using potassium [C-13]cyanide and potassium [N-15]phthalimide. In the course of the syntheses, it was found that 1,4-dibromobutane was generated from tetrahydrofuran when bromination using triphenylphosphine and tetrabromomethane took place. A high-yield preparation of monobenzyloxycarbonyl (Z) derivative of 1, a precursor for 2, was obtained using a water-soluble Z reagent, Z-DSP, in a two-phase system of alkaline solution and chloroform. All the steps for 1, 2, and 3, were aimed at minimizing the loss of stable isotopes.