A protecting group-free synthesis of deazathiamine: A step toward inhibitor design Academic Article uri icon

Overview

MeSH Major

  • Aza Compounds
  • Enzyme Inhibitors
  • Oxo-Acid-Lyases
  • Thiamine

abstract

  • The discovery of 3-deazathiamine diphosphate (deazaThDP) as a potent inhibitor analog of the cofactor thiamine diphosphate (ThDP) has highlighted the need for an efficient and scalable synthesis of deazaThDP. Such a method would facilitate development of analogs with the ability to inhibit individual ThDP-dependent enzymes selectively. Toward the goal of developing selective inhibitors of the mycobacterial enzyme 2-hydroxy-3-oxoadipate synthase (HOAS), we report an improved synthesis of deazaThDP without use of protecting groups. Tribromo-3-methylthiophene served as a versatile starting material whose selective functionalization permitted access to deazaThDP in five steps, with potential to make other analogs accessible in substantial amounts.

publication date

  • November 15, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2957563

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2010.09.053

PubMed ID

  • 20943392

Additional Document Info

start page

  • 6472

end page

  • 4

volume

  • 20

number

  • 22