Journal of Flow Chemistry

, Volume 8, Issue 1, pp 21–27 | Cite as

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

  • Aliz Szloszár
  • István M. Mándity
  • Ferenc Fülöp
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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.

Graphical abstract

Keywords

peptides synthesis peptidomimetics continuous-flow SPPS N-methylation 

Notes

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

Supplementary material

41981_2018_2_MOESM1_ESM.docx (2.7 mb)
ESM 1 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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Copyright information

© Akadémiai Kiadó 2018

Authors and Affiliations

  • Aliz Szloszár
    • 1
  • István M. Mándity
    • 1
  • Ferenc Fülöp
    • 1
    • 2
  1. 1.Institute of Pharmaceutical ChemistryUniversity of SzegedSzegedHungary
  2. 2.MTA-SZTE Stereochemistry Research GroupHungarian Academy of SciencesSzegedHungary

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