Synthetic studies towards (±)-phthalascidin 650: synthesis of a fully functionalized N-protected-α-amino-aldehyde

An efficient synthesis of fully functionalized N-protected α-amino-aldehyde (±)-13 as synthetic precursor of the tetrahydroisoquinoline alkaloid phthalascidin 650 is reported. Starting from sesamol 6, 11 steps are required to give rise to the desired N-protected α-amino-aldehyde (±)-13 in 25% overall yield. This synthetic strategy involves the elaboration of fully functionalized aromatic aldehyde 7 and its transformation into an α-amino-alcohol through a Knoevenagel condensation. The phthalimidomethyl derivative (±)-11 was then synthesised from 8 by a Bischler–Napieralski reaction, a diastereoselective hydrogenation of the resultant dihydroisoquinoline and transformed into the corresponding N-protected α-amino-aldehyde (±)-13.