An efficient synthesis of the taxane-derived anticancer agent ABT-271

J Org Chem. 2001 May 18;66(10):3330-7. doi: 10.1021/jo0057203.

Abstract

ABT-271, 1, has been identified as a promising anticancer agent. ABT-271 is a novel taxane possessing a C9-(R)-hydroxyl group as opposed to a C9-ketone which is present in Taxol and Taxotere. To further evaluate ABT-271 as a potential anticancer agent, an efficient synthesis was developed which allows the large scale synthesis of ABT-271. Ketalization of the 7,9-diol of 9-DHAB-III, 2, allows selective removal of the C13-acetate with phenyllithium. The resulting C13-hydroxyl group is then acylated using LiHMDS and beta-lactam 22 to give ABT-271 in protected form. The protecting groups were removed first by acidic hydrolysis followed by basic hydrolysis to provide ABT-271. Application of this synthetic sequence provided over 600 g of ABT-271, 1.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry*
  • Crystallization
  • Molecular Conformation
  • Taxoids*

Substances

  • ABT-271
  • Antineoplastic Agents
  • Bridged-Ring Compounds
  • Taxoids
  • taxane