Synthesis and X-ray crystal structure of the dolabellaauricularia peptide dolastatin 18

J Org Chem. 2004 Jun 11;69(12):4019-22. doi: 10.1021/jo030358o.

Abstract

A previously synthesized unit of dolastatin 10 (1), dolaphenine (Doe, 3), was converted in four steps to tripeptide 10. Subsequent condensation with carboxylic acid 11 (four steps from Meldrum's acid) provided a practical synthesis of the cancer cell growth inhibitor dolastatin 18 (2, Dhex-(S)-Leu-(R)-N-Me-Phe-Doe). The synthesis of dolastatin 18 (2) confirmed the R stereochemistry of the N-Me-Phe unit as originally assigned and unusual among amino acid components of the sea hare Dolabella auricularia. An X-ray crystal structure determination of dolastatin 18 was also completed.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Crystallography, X-Ray
  • Depsipeptides
  • Mollusca / chemistry
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology
  • Peptides / chemistry
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • Oligopeptides
  • Peptides
  • dolastatin 18