Tiazofurin Explained

Tiazofurin is a drug which acts as an inhibitor of the enzyme IMP dehydrogenase. Tiazofurin and its analogues were under investigation for potential use in the treatment of cancer,[1] though side effects such as pleuropericarditis and a flu-like syndrome precluded further development. They also show antiviral effects and may be reevaluated as potential options in the treatment of newly emerging viral diseases.[2]

Synthesis

The treatment of 1-O-Acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose [6974-32-9] (1) with trimethylsilyl cyanide gives 2,3,5-Tri-O-benzoyl-beta-D-ribofuranosyl cyanide [23316-67-8] (2). Treatment with hydrogen sulfide led to (2R,3R,4R,5R)-2-((Benzoyloxy)methyl)-5-carbamothioyltetrahydrofuran-3,4-diyl dibenzoate, PC10907289 (3). Cyclization with Ethyl bromopyruvate [70-23-5] (4) led to 2-(2,3,5-Tri-O-benzoyl-beta-D-ribofuranosyl)-4-thiazolecarboxylic Acid Ethyl Ester [60084-09-5] (5). Removal of the protecting groups with sodium methoxide afforded 2-beta-D-Ribofuranosyl-4-thiazolecarboxylic Acid Ethyl Ester [95936-53-1] (6). Amide-ester interchange by treatment with dry ammonia completed the synthesis of Tiazofurin (7).

Notes and References

  1. Popsavin M, Torović L, Svircev M, etal . Synthesis and antiproliferative activity of two new tiazofurin analogues with 2'-amido functionalities . Bioorg. Med. Chem. Lett. . 16 . 10 . 2773–6 . 2006 . 16495053 . 10.1016/j.bmcl.2006.02.001.
  2. De Clercq E . C-Nucleosides To Be Revisited . Journal of Medicinal Chemistry . 59 . 6 . 2301–11 . March 2016 . 26513594 . 10.1021/acs.jmedchem.5b01157 .