The Synthesis of (2R)-Aziridine-2-carboxylic Acid Containing Dipeptides

Authors

  • Samo Kuzmič University of Ljubljana Faculty of pharmacy The Chair of Pharmaceutical Chemistry Aškerčeva cesta 7 SI-1000 Ljubljana Slovenia
  • Martina Hrast University of Ljubljana Faculty of pharmacy The Chair of Pharmaceutical Chemistry Aškerčeva cesta 7 SI-1000 Ljubljana Slovenia http://orcid.org/0000-0003-0488-2445
  • Rok Frlan University of Ljubljana Faculty of pharmacy The Chair of Pharmaceutical Chemistry Aškerčeva cesta 7 SI-1000 Ljubljana Slovenia http://orcid.org/0000-0003-0956-5537

DOI:

https://doi.org/10.17344/acsi.2021.6673

Keywords:

Dipeptides, aziridines, biomarkers, warheads, antibacterial agents

Abstract

Optimized conditions for the synthesis of fully deprotected (2R)-aziridine containing dipeptides are described. Preparation of fully protected N- and C- terminal aziridine containing dipeptides was found to be straightforward and high yielding for the majority of compounds, whereas their full deprotection was possible only for C-terminal analogs. Deprotection of N-terminal derivatives using standard procedures of peptide chemistry was found difficult providing only mixtures of unidentifiable products. The described molecules have potential as building blocks in synthetic chemistry, in the chemical biology arena, as covalent modifiers, and as biomarkers.

Author Biographies

Samo Kuzmič, University of Ljubljana Faculty of pharmacy The Chair of Pharmaceutical Chemistry Aškerčeva cesta 7 SI-1000 Ljubljana Slovenia

Samo Kuzmič received his Master's degree in Pharmacy from Faculty of Pharmacy, University of Ljubljana in 2018. Later that year, he joined Sandoz Development Center in Slovenia, where he is currently working as a Scientist in department of Prototype Analytics. His work focuses on in silico stability predictions, evaluation of degradation mechanisms and degradation products. His main purpose is to develop a stable generic products and to enable people around the world access to high-quality medicine

Martina Hrast, University of Ljubljana Faculty of pharmacy The Chair of Pharmaceutical Chemistry Aškerčeva cesta 7 SI-1000 Ljubljana Slovenia

Martina Hrast is a researcher at the University of Ljubljana, Faculty of Pharmacy in Ljubljana (Slovenia). In 2009 she received a masters degree in pharmacy and in 2013 a PhD degree. During her professional career, she received numerous awards - a Solemn award for extraordinary pedagogic, research and artistic achievements,  Krka Prize for PhD thesis »Design and synthesis of inhibitors of Mur ligases and D-alanine: D-alanine ligase«, dean award and Faculty Prešeren award for a graduate thesis. Her research interests are in the field of medicinal chemistry of antibacterial compounds and organic synthesis.

Rok Frlan, University of Ljubljana Faculty of pharmacy The Chair of Pharmaceutical Chemistry Aškerčeva cesta 7 SI-1000 Ljubljana Slovenia

Rok Frlan is an assistant professor at the University of Ljubljana, Faculty of Pharmacy in Ljubljana (Slovenia). In 2004 he received a masters degree in pharmacy and in 2009 a PhD degree on the design, synthesis and biological testing of novel small molecule inhibitors of Mur inhibitors as potential antibacterial agents. His post-doctorate studies were conducted in 2009 - 2010 at the Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes (France) under the direction of Christine Gravier-Pelletier on the synthesis of bacterial transferase MraY inhibitors. Rok received two Krka Prizes in 2004 for his research in the design and synthesis of Ag85C inhibitors as potential antitubercular drugs and in 2009 (Special prize) for his research in the design, synthesis, and evaluation of MurC and D inhibitors.  In 2016 the Chamber of Commerce and Industry of Slovenia awarded him the golden prize for the innovation on work on the green and efficient synthesis of Sitagliptin. His research interests are in the field of medicinal chemistry of antibacterial compounds and organic synthesis. His pedagogic work includes the experimental practice of medicinal chemistry and instrumental pharmaceutical chemistry.

Downloads

Additional Files

Published

14.06.2022

Issue

Vol. 69 No. 2 (2022)

Section

Organic chemistry

License

Except where otherwise noted, articles in this journal are published under the Creative Commons Attribution 4.0 International License