Synthesis of novel C2-C3'N-linked macrocyclic taxoids by means of highly regioselective Heck macrocyclization

Org Lett. 2003 Oct 2;5(20):3733-6. doi: 10.1021/ol0354627.

Abstract

[reaction: see text] Novel C2-C3'N-linked macrocyclic taxoids are synthesized using intramolecular Heck reaction in the key step. Macrocyclization proceeds with high regioselectivity in good yield. Taxoids bearing an olefin moiety at C2 and an iodide at C3'N give exo-products exclusively. However, the endo-products are formed with up to 100% regioselectivity just by switching the positions of the olefin and the iodide moieties. Some of these macrocyclic taxoids are significantly cytotoxic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkenes / chemistry
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cyclization
  • Humans
  • Hydrocarbons, Iodinated / chemistry
  • Inhibitory Concentration 50
  • Stereoisomerism
  • Taxoids / chemical synthesis*
  • Taxoids / chemistry
  • Taxoids / pharmacology

Substances

  • Alkenes
  • Antineoplastic Agents
  • Hydrocarbons, Iodinated
  • Taxoids