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

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.

• Authors: George R Pettit, Fiona Hogan, Delbert L Herald
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 69 Issue 12 Pg. 4019-22 (Jun 11 2004) ISSN: 0022-3263 [Print] United States
• PMID: 15176826 (Publication Type: Journal Article, 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.)

Chemical References

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

Topics

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