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Flow Processes/ Continuous Processing

The use of flow chemistry techniques for SPPS can give processes that use less reagents and solvents, are more predictable, and more amenable to automation and other green approaches such as on line solvent recovery. Different reactor configurations can be employed in continuous SPPS. Examples include packed bed flow reactors or a train of continuously stirred tank reactors (CSTR).
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Gordon, C. P.  The renascence of continuous-flow peptide synthesis – an abridged account of solid and solution-based approaches. Org. Biomol. Chem. 2018, 16, 180–196.

Farkas, V.; Ferentzi, K.; Horváti K.; Perczel, A. Cost-Effective Flow Peptide Synthesis: Metamorphosis of HPLC. Org. Process Res. Dev. 2021, 25, 182–191.

Gates, Z. P.; Hartrampf, N. Flow-based SPPS for protein synthesis: A perspective. Pep. Sci. 2020, 112, e24198.

Nuño, M.; Laude, V. Solid-phase peptide synthesis: Recent advances through adoption of continuous flow. Chemistry Today 2020, 38(2), 26–29.

Ludemann-Homourger, O.; Möller, P.; Kuster, F. Downstream Processes for Peptide Manufacturing: Optimization Strategy and Latest Technical Trends. Chemistry Today 2021, 39(2), 40–45.

Al Musaimi, O.; Summers, B. D.; Basso, A.; de la Torre, B. G.; Albericio, F.; Serban, S. Combining solid phase synthesis and chromatographic purification for efficient peptide manufacture. Chemistry Today 2020, 38(2), 18–21.

Pennington, M. W.; Karounos, D.; Bai, C.  Alternative Strategies Which Help Improve Sustainability And “Green” Peptide Manufacturing. Chemistry Today 2021, 39(2), 36–39.

Ormerod, D.; Noten, B.; Dorbec, M.; Andersson, L.; Buekenhoudt, A.; Goetelen, L. Cyclic Peptide Formation in Reduced Solvent Volumes via In-Line Solvent Recycling by Organic Solvent Nanofiltration. Org. Process Res. Dev. 2015, 19, 841–848.