Spectrophotometric monitoring in continuous-flow Boc-based solid-phase peptide synthesis

: It has been demonstrated that SPPS with Boc amino group protection can be monitored spectrophotometrically if it is performed in a continuous‐flow reactor of variable volume. It is shown that this approach provides useful and adequate evidence on the beginning/end‐point of most steps of the SPPS cycle. At the deprotection step the spectrophotometric monitoring enables real‐time recording of the initial and final moments of the process. When synthesizing a ‘difficult’ polyalanine sequence, we were able to monitor variation in the deprotection dynamics associated with the aggregation phenomena. The time actually necessary for the Boc protecting group removal appeared to be significantly smaller than that usually preset in the available Boc‐SPPS protocols.