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.