Improved Synthesis of MDL 73811 - a Potent AdoMetDC Inhibitor and Anti-Trypanosomal Compound

  • Synthesis (Stuttg). 2016 Jul;48(13):2065-2068. doi: 10.1055/s-0035-1561608.
Anthony J Brockway  1 ,  Casey C Cosner  1 ,  Oleg A Volkov  2 ,  Margaret A Phillips  2 ,  Jef K De Brabander  1
Affiliations
  • 1. Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
  • 2. Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas,6001 Forest Park Road, Dallas, Texas 75390-9041, United States.
PMID: 27482123 DOI: 10.1055/s-0035-1561608
Abstract

An improved synthesis of MDL 73811 - a potent AdoMetDC (S-adenosylmethionine decarboxylease) inhibitor and anti-trypanosomal compound with in vivo activity has been completed in four steps from commercially available 2',3'-O-isopropylideneadenosine. Utilization of Mitsunobu chemistry was crucial for the reliable and scalable introduction of the 5'-methylamine moiety, which was problematic using traditional activation/displacement chemistry as previously reported. All reactions in this synthesis were run on gram-scale resulting in a five-fold increase in yield over the original synthesis.

Keywords
drug discovery; nucleosides.
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