Improved synthesis of a [4.4]-spirolactam β-turn mimetic as surrogate of the didemnin side chain dipeptide Pro-N-Me-D-Leu

Article abstract of DOI:10.1016/j.tet.2004.04.052

An efficient synthesis of [4.4]-spirolactam restricted derivatives of the didemnin side chain dipeptide L-Pro-N-Me-D-Leu is described. This methodology involves: (a) peptide coupling of N-Boc-2-allylproline with D-Leu-OBn; (b) OsO₄/NaIO₄ mediated allyl oxidation and intramolecular cyclization to the corresponding cyclic hemiaminals; and (c) NaBH₄ mediated reduction of an intermediate N-acyliminium ion. This synthetic strategy gave significant better results than the previously reported strategies for the synthesis of [4.4]-spirolactam β-turn mimetics.