Fig. 2. Preparation of the cyclic peptides via methionine alkylation. (A) Met bis-alkylation of peptide 1 with different linkers. Peptides were dissolved in a solution of 1% HCOOH MeCN/H2O (30 : 70, v/v) and stirred for 24 h at room temperature. The optimization process was summarized in Table S1.† NR: no reaction. (B) ESI-MS and 1H-NMR spectra of peptide 1d in CD3OD. (C) Different peptide sequences and loop sizes cyclized by Met bis-alkylation. (D) Peptide 10 with three Mets reacted with 1,3,5-tris(bromomethyl) benzene to generate bicyclic peptide 10j. Conversions: [desired product/(desired product + starting material)] were determined by integration of reverse-phase HPLC.
