The synthesis of oxa-analogues and homologues of naturally occurring polyamines

A number of polyamine era-analogues 14a-d, 19 have been synthesised. Spermidine era-analogues and homologues 14 were made from N-(aminooxypropyl)phthalimide 8a which was obtained either from the Fmoc-deprotection of N-[3-(Fmoc-amino)propoxy]phthalimide 4a or from the reaction between 3-bromopropylamine and N-hydroxyphthalimide, both reactions involving an unusual rearrangement mechanism. Sulphonated derivatives 9, 16, upon Mitsunobu condensation with N-protected 3-aminopropanol or N-alkylation with N-(bromoalkyl)phthalimides, afforded the fully protected spermidine and spermine oxa-analogues and homologues. Subsequent sequential deprotection gave spermidine analogues 14. Using the same strategy, spermine oxa-analogue 19 was synthesised.