Synthesis of glycoglycerolipid of 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-α-D-glucosyl)-sn-glycerol and its analogues, inhibitors of human Myt1-kinase

Carbohydr Res. 2012 Jul 1:355:6-12. doi: 10.1016/j.carres.2012.04.005. Epub 2012 Apr 26.

Abstract

A glycoglycerolipid 1a isolated from a marine alga showed inhibition to Myt1 kinase with IC(50) of 0.12 μg/mL. We synthesized 1a and its seven analogues (1b-h) in an efficient method with high stereoselectivity. The process employed trichloroacetimidate donor 4b at low substrate concentration to achieve high α-selectivity (α/β=33:1) in glycosylation reaction. The present synthesis provided various acyl derivatives required for the study on the structure-activity relationship later.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Glycolipids / chemical synthesis
  • Glycolipids / chemistry
  • Glycolipids / pharmacology*
  • Glycosylation
  • Humans
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 1,2-dipalmitoyl-3-(N-palmitoyl-6-amino-6-deoxyglucosyl)-sn-glycerol
  • Glycolipids
  • Membrane Proteins
  • Protein Kinase Inhibitors
  • glycerolglycolipids
  • Protein-Tyrosine Kinases
  • PKMYT1 protein, human
  • Protein Serine-Threonine Kinases