Accelerated Synthesis of Protected Peptides in a Continuous‐Flow Fixed‐Bed Reactor

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

doi:10.1002/slct.201701489

Cited by 11 publications

(5 citation statements)

References 76 publications

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“…in the same year (Table 2 , entry 9). [107] They used a set‐up consisting of an HPLC pump, autosampler, column thermostat, and PEEK column. [101] They synthesized the LFE‐2‐CTC‐PS sequence manually as a starting sequence for the coupling in flow.…”

Section: Discussionmentioning

confidence: 99%

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

2022

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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.

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Section: Discussionmentioning

confidence: 99%

“…A fast and sustainable flow method for the synthesis of protected peptide on solid support was developed by Szloszar et al in the same year (Table 2, entry 9). [107] They used a set-up consisting of an HPLC pump, autosampler, column thermostat, and PEEK column. [101] They synthesized the LFE-2-CTC-PS Scheme 6.…”

Section: Chemsuschemmentioning

confidence: 99%

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

2022

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“…Amino acid equivalents needed to achieve high coupling yields were decreased to 1.5‐3.0 equivalents in a mesoscale synthesizer and the synthesis of multiple short peptides was demonstrated. [ 100,101 ] How much could coupling equivalents and solvents be reduced in AFPS? Can “greener” and potentially less toxic coupling agents, such as (1‐cyano‐2‐ethoxy‐2‐oxoethylidenaminooxy)dimethylamino‐morpholino‐carbenium hexafluorophosphate (COMU), fluoro‐ N , N , N ′, N′ ‐tetramethylformamidinium hexafluorophosphate derivatives or 1‐propanephosphonic anhydride (T3P) be used in AFPS, too?…”

Section: Related Research Areas and Future Directionsmentioning

confidence: 99%

Flow‐based SPPS for protein synthesis: A perspective

Gates

Hartrampf

2020

Peptide Science

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Flow‐based approaches to solid phase peptide synthesis (SPPS) have been pursued since the method's early days, with anticipated gains in speed, reaction monitoring, and ease of automation. Here, we discuss how these advantages are being realized by synthesis at elevated temperature, facilitated by a 'preheat/activation' loop. This important modification both accelerates peptide synthesis—providing a wealth of new data from in‐line monitoring—and in conjunction with an optimized protocol, extends the length of peptides routinely accessible by stepwise synthesis. Streamlined synthesis of longer peptides will address a major challenge in chemical protein synthesis: preparation of peptide segments for use in chemical ligation. The context of recent results in flow‐based SPPS is discussed, highlighting remaining challenges and future opportunities.

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“…With the increasing popularity of flow chemistry-based synthesis, their use is likely to increase [4][5][6]. A column is the most common configuration for a packed-bed reactor.…”

Section: Introductionmentioning

confidence: 99%

Cuboid Packed-Beds as Chemical Reactors?

Ghosh

2018

Processes

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Columns are widely used as packed-bed or fixed-bed reactors in the chemical process industry. Packed columns are also used for carrying out chemical separation techniques such as adsorption, distillation, extraction and chromatography. A combination of the variability in flow path lengths, and the variability of velocity along these flow paths results in significant broadening in solute residence time distribution within columns, particularly in those having low bed height to diameter ratios. Therefore, wide packed-column reactors operate at low efficiencies. Also, for a column of a particular bed height, the ratio of heat transfer surface area to reactor volume varies inversely as the radius. Therefore, with wide columns, the available heat transfer area could become a limiting factor. In recent papers, box-shaped or cuboid packed-bed devices have been proposed as efficient alternatives to packed columns for carrying out chromatographic separations. In this paper, the use of cuboid packed-beds as reactors for carrying out chemical and biochemical reactions has been proposed. This proposition is primarily supported in terms of advantages resulting from superior system hydraulics and narrower residence time distributions. Other potential advantages, such as better heat transfer attributes, are speculated based on geometric considerations.

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Accelerated Synthesis of Protected Peptides in a Continuous‐Flow Fixed‐Bed Reactor

Cited by 11 publications

References 76 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 SPPS for protein synthesis: A perspective

Cuboid Packed-Beds as Chemical Reactors?

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