Synthetic development of sugar amino acid oligomers towards novel podophyllotoxin analogues

  • Bioorg Med Chem. 2021 Dec 15:52:116501. doi: 10.1016/j.bmc.2021.116501.
Megan Bouchard  1 ,  Thomas Tremblay  1 ,  Marie-Pier Paré-Lacroix  1 ,  Mathieu Gagné-Boulet  2 ,  Sébastien Fortin  2 ,  Denis Giguère  3
Affiliations
  • 1. Département de Chimie, 1045 av. De la Médecine, Université Laval, Québec City, QC G1V 0A6, Canada.
  • 2. Centre de recherche du CHU de Québec-Université Laval, Axe oncologie, Hôpital Saint-François d'Assise, 10 rue de l'Espinay, Quebec City, QC G1L 3L5, Canada; Faculté de Pharmacie, 1050 avenue de la Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada.
  • 3. Département de Chimie, 1045 av. De la Médecine, Université Laval, Québec City, QC G1V 0A6, Canada. Electronic address: [email protected].
PMID: 34837817 DOI: 10.1016/j.bmc.2021.116501
Abstract

In this work, we have developed an approach for the synthesis of sugar amino acid oligomers based on the glucosamine scaffold. We found that the solid-phase approach was unsuccessful for the preparation of sugar amino acid oligomers and the limitation of the liquid-phase approach revolved around the low solubility of larger oligomers. Nevertheless, this strategy allowed the coupling of alkynylated carbohydrate Amino acids with podophyllotoxin-bearing an azide functional group yielding novel podophyllotoxin analogues. Due to their low solubility, the antiproliferative study revealed no Anticancer activity of these newly synthesized analogues.

Keywords
Antiproliferative compounds; Etoposide; Glycomimetics; Podophyllotoxin analogues; Sugar amino acids.