Synthesis of anti-tumour phosphatidylinositol analogues from glucose by the use of ring-closing olefin metathesis

Org Biomol Chem. 2004 Oct 21;2(20):2951-7. doi: 10.1039/B411021H. Epub 2004 Sep 16.

Abstract

A divergent strategy is described for synthesis of the novel phosphatidylinositols 1-3. The synthetic approach commences from benzyl-protected methyl 6-iodo-6-deoxy-alpha-D-glucopyranoside, which undergoes zinc-mediated reductive fragmentation followed by vinyl Grignard addition and ring-closing metathesis to afford the key conduritol B intermediate 7. This can trifurcate to form three different benzyl-protected myo-inositol headgroups 4-6, which after phosphorylation and attachment of the glycerolipid part give phosphatidylinositols 1-3. Preliminary biological testing against human colon adenocarcinoma cells reveals that analogues 1-3 are significant anti-tumour agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Alkenes / chemistry*
  • Antineoplastic Agents / chemical synthesis*
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy
  • Cyclohexanes / chemistry
  • Glucose / chemistry*
  • Humans
  • Models, Chemical
  • Molecular Structure
  • Phosphatidylinositols / chemistry*

Substances

  • Alkenes
  • Antineoplastic Agents
  • Cyclohexanes
  • Phosphatidylinositols
  • Glucose