Solid-phase synthesis of polyamines using a Dde-linker: philanthotoxin-4.3.3 via an on-resin Mitsunobu reaction

A Dde linker/solid-phase procedure for the stepwise construction of polyamines is illustrated with the synthesis of philanthotoxin-4.3.3. Resin-bound 4-aza-1,7-heptanediamine was N4-protected and N7-activated in a single operation with 2-nitrobenzenesulphonyl chloride. Alkylation with N-Fmoc-4-aminobutanol under Mitsunobu conditions completed the polyamine backbone. Deprotection of the sulphonamide groups was readily achieved with thiolates in DMF at room temperature.