Development of a Scalable Synthesis of Tofogliflozin

J Org Chem. 2016 Mar 4;81(5):2148-53. doi: 10.1021/acs.joc.5b02734. Epub 2016 Feb 19.

Abstract

An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described. A key factor in the synthesis of 1 was the selection of the purpose-designed protecting group, which plays a strategic role in protection, chemoselective activation, and crystalline purification. The developed and optimized method made it possible to prepare 1 on a multidecagram scale without any column chromatography.

MeSH terms

  • Benzhydryl Compounds / chemical synthesis*
  • Benzhydryl Compounds / chemistry
  • Glucose / chemistry*
  • Glucosides / chemical synthesis*
  • Glucosides / chemistry
  • Molecular Structure
  • Sodium-Glucose Transporter 2 / chemistry*
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Benzhydryl Compounds
  • Glucosides
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucose
  • 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol