The preparation of 14-membered macrocycles from a resin-bound orthogonally protected lysine residue is described. Reductive alkylation of the a-nitrogen followed by acylation with an Fmoc-aminoacid provides a protected dipeptide precursor. Removal of the Fmoc-group, acylation with a succinic anhydride, methyltrityl-group removal and macrocyclization provides the desired macrocycles, after TFA cleavage, in excellent yield and purity.

 
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