A general methodology for the total synthesis of N-alkyl- and acylpolyamine derivatives is described which is based on the coupling of suitable N-tritylamino acids with amines followed by lithium aluminium hydride reduction of the thus obtained amides.
Allfourisomers of the spermine alkaloid kukoamine were unambiguously prepared through diacylation with O,O′-dibenzylcaffeyl chloride of suitably protected (benzyl and/or trityl groups) spermine derivatives, assembled on solid and/or in liquid phase using β-alanine and γ-aminobutyric acid, followed by simultaneous N- and O- deprotection and double bond reduction using catalytic hydrogenation.
Linear N-benzyl-N′-trityl-α,Ï-diamines and N α, N Ï-ditritylpolyamines were efficiently converted into the corresponding N-(1-benzyltetrazol-5-yl)-substituted derivatives upon treatment with benzyl isothiocyanate followed by reaction of the thus-obtained thioureas with azidotrimethylsilane under Mitsunobu reaction conditions.