Synthesis and X-ray crystal structure of the dolabellaauricularia peptide dolastatin 18.
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.
Pettit
George R
GR
Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Hogan
Fiona
F
Herald
Delbert L
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D047630:Depsipeptides; D008974:Mollusca / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; D010455:Peptides; C488613:dolastatin 18