Sustainable synthesis of N-methylated peptides in a continuous-flow fixed bed reactor

Szloszár, Aliz; Mándity, István M.; Fülöp, Ferenc

doi:10.1007/s41981-018-0002-9

Cited by 7 publications

(3 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A fast and sustainable continuous‐flow solid‐phase peptide synthesis protocol of mono‐ and multiple‐ N ‐methylated peptides was developed by Fülöp and co‐workers in 2018, [167] relying on their previous work (Table 4 , entry 5). [101] A mixture of 1.5 equiv.…”

Section: Discussionmentioning

confidence: 99%

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

2022

View full text Add to dashboard Cite

Formation of amide bonds is of immanent importance in organic and synthetic medicinal chemistry. Its presence in "traditional" small-molecule active pharmaceutical ingredients, in linear or cyclic oligo-and polypeptidic actives, including pseudopeptides, has led to the development of dedicated synthetic approaches for the formation of amide bonds starting from, if necessary, suitably protected amino acids. While the use of solid supported reagents is common in traditional peptide synthesis, similar approaches targeting amide bond formation in continuous-flow mode took off more significantly, after a first publication in 2006, only a couple of years ago. Most efforts rely upon the transition of traditional approaches in flow mode, or the combination of solid-phase peptide synthesis principles with flow chemistry, and advantages are mainly seen in improving space-time yields. This Review summarizes and compares the various approaches in terms of basic amide formation, peptide synthesis, and pseudopeptide generation, describing the technological approaches and the advantages that were generated by the specific flow approaches. A final discussion highlights potential future needs and perspectives in terms of greener and more sustainable syntheses.

show abstract

Section: Discussionmentioning

confidence: 99%

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

2022

View full text Add to dashboard Cite

show abstract

“…[17] Fülöp and coworkers demonstrated the flow synthesis of unmodified and N-methylated peptides with only 1.5 equivalents of amino acids and coupling reagents in a flow-based system. [18,19] For batch-SPPS, much research has been devoted to the search for new SPPS-compatible solvents to replace polar, aprotic DMF. However, despite the recommendation of numerous green solvent alternatives, none of them have been tested in flow-based SPPS.…”

Section: Automated Fast-flow Peptide Synthesis (Afps)mentioning

confidence: 99%

Flow-based Methods in Chemical Peptide and Protein Synthesis

Schiefelbein

Hartrampf

2021

Chimia

View full text Add to dashboard Cite

Flow chemistry has emerged as a powerful method for on-demand chemical synthesis and modification of peptides and proteins. Herein, we discuss the characteristics of flow chemistry and how they are applied to various aspects of peptide chemistry. We highlight recent advances in automated flow-based peptide synthesis, which extend the length of peptides routinely accessible to single-domain proteins and allow for the collection of time-resolved synthesis data. Applications of this data for the prediction of synthesis outcome and the potential for the development of more sustainable synthesis methods are also discussed. Finally, we will review solutionphase approaches, including flow-based ligation strategies and peptide cyclization. Throughout this review, the current challenges and potential future developments are highlighted.

show abstract

“…Mándity et al first constructed a high-performance liquid chromatography (HPLC)-based synthesizer of yet-to-be-tested efficiency, primarily for coupling β-amino acid residues using 1.5–3 equiv. of reagent excess at 70 °C and 60 bar pressure, and the instrumentation and protocols have since been under continuous development. , Mijalis et al developed an impressively fast technique, reaching a breathtaking coupling and deprotection rate of 40–120 s/cycle, but at high cost by using 20–100 molar equivalent reagent excess at high temperature (90 °C) …”

Section: Introductionmentioning

confidence: 99%

Cost-Effective Flow Peptide Synthesis: Metamorphosis of HPLC

Farkas

Ferentzi

Horváti

et al. 2021

Org. Process Res. Dev.

View full text Add to dashboard Cite

We present the further development and fine-tuning of an efficient, economic (≤3 equivalents of activated amino acid ), and environmentally friendly (6 mL organic waste/cycle) procedure for peptide synthesis using a fast amino acid coupling reaction (1.7 min). The designed setup can assist the synthesis of highly pure (>80%) raw materials even for long (up to 30 aa.) and/or difficult sequences. The significant reduction of the coupling time by using the effective PyAOP and N,N′-diisopropylcarbodiimide/ HOBt coupling reagents was achieved, and virtually racemization-free (L-His/D-His <1−5%) peptides can now be synthesized, even at higher column temperature: T = 70 °C. The purity of the product and the efficiency of the synthesis were evaluated using different solid phase supports and protocols. We successfully completed the synthesis of "difficult" sequences [e.g., insulin B-chain and cecropin A(1−7)-melittin(2−9) hybrid peptide] wasting only a fraction of the organic solvents compared to other methods, furthering peptide chemistry toward a greener approach.

show abstract

Sustainable synthesis of N-methylated peptides in a continuous-flow fixed bed reactor

Cited by 7 publications

References 52 publications

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

Flow-based Methods in Chemical Peptide and Protein Synthesis

Cost-Effective Flow Peptide Synthesis: Metamorphosis of HPLC

Contact Info

Product

Resources

About