Use of the Mitsunobu reaction in the synthesis of orthogonally protected α,β-diaminopropionic acids

Orthogonally protected α,β-diaminopropionic acids have been synthesised in good yields by the reaction of N-trityl l-serine esters with N-substituted sulfonamides under Mitsunobu reaction conditions (DEAD, PPh3, THF). The best isolated yields were obtained when N-Boc p-toluenesulfonamide was used as the nitrogen nucleophile precursor in the Mitsunobu reaction. Subsequently, the N-trityl group was efficiently replaced with the more stable allyloxycarbonyl (alloc) group.

Graphical abstractThe reaction of N-trityl l-serine esters with N-substituted sulfonamides (e.g., Boc-NH-Ts) under Mitsunobu conditions gives orthogonally protected α,β-diaminopropionic acids in good yields.Download full-size image