Novel syntheses of polyamines and the analysis of effects of substituted polyamines on protein and polyamine syntheses using Ps. (Kim) and Escherichia coli extracts

The object of this study was twofold. One aspect of this work explored simple ways to synthesize substituted and unsubstituted polyamines. The other aspect of this work examined the effects of hydroxy and N-(amino) substituted polyamines on bacterial protein and polyamine syntheses.; Fairly facile syntheses of substituted and unsubstituted polyamines were accomplished using several methods. One novel approach, which lead to the generation of the widest array of polyamines, was a versatile reaction scheme involving a ring opening reaction of unsubstituted or N-substituted cyclic imides of different ring size with an amine or hydrazine to form the corresponding alkanediamide or hydrazidoalkanamide intermediates, which were ultimately reduced to polyamines. Another novel sequence used a synthetically specific step which led to the incorporation of a 2-hydroxybutanediamine segment in the ultimately formed polyamine. This sequence used 1,3-dipolar reactions to form specific structural intermediates which were ultimately reducible to the corresponding polyamines. One conventional sequence involved the conversion of substituted or unsubstituted diacids to diesters, which were converted to alkanediamides or dihydrazides; and then to diamines and dihydrazines. Another conventional sequence utilized amino cyanoethylation reactions, some of which could be used to form specific intermediates which were then reduced to polyamines.; A number of the synthesized hydroxyl and N-(amino) substituted polyamines were tested to determine their effect on bacterial protein and polyamine syntheses. The hydroxy but not N-(amino) substituted putrescine and spermidine analogues were generally capable of replacing the naturally occurring polyamines in the promotion of protein synthesis using E. coli or Ps. (Kim) extracts. The hydroxy and N-(amino) substituted polyamines were not substrates for S-adenosylmethionine decarboxylase (SAM DC) in the polyamine synthesis studies. Residual putrescine in the dialyzed polyamine synthesis extracts did react with the SAM DC in the presence of most of the polyamines except for N-(amino)putrescine and N,N{dollar}spprime{dollar}-bis(amino)putrescine. When equimolar amounts of C{dollar}sp{lcub}14{rcub}{dollar} labeled putrescine and one of derivatized polyamines were added to the polyamine synthesis system the labeled putrescine was converted to spermidine except in the presence of the N-(amino) substituted putrescines.