Synthesis and X-ray crystal structure of the dolabellaauricularia peptide dolastatin 18
Pettit, G.R.; Hogan, F.; Herald, D.L.
Journal of Organic Chemistry 69(12): 4019-4022
ISSN/ISBN: 0022-3263 PMID: 15176826 DOI: 10.1021/jo030358o
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.