Improved Synthesis of the Unnatural Amino Acids AHMOD and AMD, Components of the Anticancer Peptaibol Culicinin D

J Org Chem. 2015 Sep 4;80(17):8631-6. doi: 10.1021/acs.joc.5b01265. Epub 2015 Aug 14.

Abstract

An improved second-generation synthesis of the unnatural amino acid components of the anticancer peptaibol culicinin D has been developed. With a protected glutamic acid derivate as the starting material, the process readily delivered the Fmoc-protected free acid derivatives of AHMOD ((2S)-amino-(6R)-hydroxy-(4S)-methyl-8-oxodecanoic acid) and AMD ((2S)-amino-(4S)-methyldecanoic acid) required to support solid phase peptide synthesis (SPPS) for structure-activity studies of the natural product. The same approach also provides improved access to pipecolic acid derivatives. A novel Wittig reagent for one-carbon homologation of aldehydes, developed during this work, is also reported.

MeSH terms

  • Aldehydes / chemistry*
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Peptaibols / chemistry*
  • Peptaibols / pharmacology*
  • Solid-Phase Synthesis Techniques
  • Stereoisomerism

Substances

  • Aldehydes
  • Amino Acids
  • Antineoplastic Agents
  • Oligopeptides
  • Peptaibols
  • culicinin D