SPOT synthesis and PIPE principles. (A): General concept of the SPOT synthesis. (B): Key steps of the process of inverted peptides. (a): coupling of the bromoacetyl moiety (1 M in DMF, 4-time coupling, 15 min reaction each), (b): selective cysteine detritylation with TFA (7% in DCM), (c): macrocycle formation, (d): one-pot acid cleavage and side chain deprotection (60% TFA followed by 90% TFA).