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

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Abstract

A rapid, simplified and highly efficient continuous-flow solid-phase peptide synthesis technology is reported for the direct synthesis of mono and multiple N-methylated cyclic alanine and valine peptides. Through an optimization study, we find that only 1.5 equivalents of the amino acids are sufficient for the couplings to maintain excellent conversions. Importantly, the technology is outstandingly sustainable, since three chemical steps are cancelled from the procedure and low amount of solvent is used, compared to traditional technologies. Furthermore, it is also applicable to the coupling of challenging amino acids, since pentavalines were constructed with high yield. The technology was successfully upscaled and peptide cyclization was carried out too.

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Acknowledgements

We are grateful to the Hungarian Research Foundation (OTKA No. K 115731). The financial support of the GINOP-2.3.2-15-2016-00014 project is acknowledged. Supported by the ÚNKP-16-4-III New National Excellence Program of the Ministry of Human Capacities

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Authors and Affiliations

  1. Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary

    Aliz Szloszár, István M. Mándity & Ferenc Fülöp

  2. MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, Eötvös u. 6, Szeged, H-6720, Hungary

    Ferenc Fülöp

Authors
  1. Aliz Szloszár
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  2. István M. Mándity
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  3. Ferenc Fülöp
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Correspondence to Ferenc Fülöp.

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Supporting Information Available: Supplementary data (experimental procedures, HPLC-MS chromatograms and mass spectra, NMR spectrum) associated with this article can be found in the online version at: doi:xxxxxxxxx (DOCX 2740 kb)

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Szloszár, A., Mándity, I.M. & Fülöp, F. Sustainable synthesis of N-methylated peptides in a continuous-flow fixed bed reactor. J Flow Chem 8, 21–27 (2018). https://doi.org/10.1007/s41981-018-0002-9

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  • DOI: https://doi.org/10.1007/s41981-018-0002-9

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