Syntheses of [5, 8-¹³C₂]- and [1, 12-<13>C₂]Spermine Using Potassium [¹³C]Cyanide as the ¹³C Source

Abstract

[5, 8-¹³C₂]Spermine and [1, 12-¹³C₂]spermine were prepared using [¹³C]KCN as the source of the label. By reaction of the latter with 1, 2-dibromoethane and ethylene chlorohydrin, the corresponding [1, 4-¹³C₂]succinodinitrile and [CN-¹³C]ethylene cyanohydrin were respectively obtained. The reaction conditions were carefully adjusted so as to optimize the yields of the ¹³C-enriched intermediates. The nitrile residues were then reduced using sodium trifluoroacetoxyborohydride in tetrahydrofuran. [1, 4-¹³C₂]Putrescine and [3-¹³C]3-aminopropanol were thus obtained. The latter was transformed into its [3-¹³C]3-carbobenzyloxyamidopropyl bromide derivative. The syntheses of [5, 8-¹³C₂]spermine from the [1, 4-¹³C₂]putrescine precursor and N-(3-bromopropyl)phthalimide, and of [1, 12-¹³C₂]spermine from N, N'-bisbenzylputrescine and the [3-¹³C]3-carbobenzyloxyamidopropyl bromide precursor were then carried out using our previously reported methods, which were modified so as to maximize the yields of the ¹³C-enriched products.