Chemistry of Naturally Occurring Polyamines. 10. Nonmetabolizable Derivatives of Spermine and Spermidine

Article abstract of DOI:10.1021/jo00375a018

Polyamine oxidases (PAO's) play an important role in the oxidative metabolism of spermidine, spermine, and their derivatives.Since the actual oxidation step involves deprotonation at the α-carbon(s) of the amine, gem-dimethyl substitution at those sites should retard catabolism.Moreover, synthetic methylated analogues of known biologically active polyamine conjugates may be expected to display enhanced activity and/or longer duration of action.This paper describes the synthesis of stable hydrochloride salts of five gem-dimethylspermidines 8-12 and two spermine analogues 13 and 14 that were designed to act as PAO inhibitors and to serve as useful probes of complex polyamine biosynthesis.