Solution Forms of Bouvardin and Relatives from NMR Studies. 6-O-Methylbouvardin

Robert B. Bates, Jack R. Cole, Joseph J. Hoffmann, George R. Kriek, Gary S. Linz, Sterling J. Torrance

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

1H and 13C NMR studies indicate that the predominant stereoisomer and conformer in solution for the potent natural antitumor agents deoxybouvardin (1), bouvardin (2), and the newly isolated and equally active 6-O-methylbouvardin (3) is that found in the solid state by X-ray diffraction. Unusual features in the spectra, all in the vicinity of the 14-membered ring, include an aromatic proton absorbing unusually far upfield at 4.35, a vicinal H-C-O-H coupling constant of 10.2 Hz, aryl carbons ortho to an ether oxygen absorbing at 5 124.2-125.9, and a geminal coupling constant of-20 Hz between the methylene protons in a tyrosine residue. A minor stereoisomer (~15%) separated by a 20.6 kcal/mol barrier is observed for 1-3; variable-temperature 1H NMR studies on model N-methyl peptides indicate this stereoisomer to differ in rotation about the Tyr-5 and/or Tyr-3 amide bond. Since the antitumor activities of six compounds differing in substitution on Tyr-5 and Tyr-6 do not vary appreciably while a change in Tyr-3 results in loss of activity, the rigid 14-membered ring portion of the molecule is not the active part but serves to get the rest of the molecule into the active conformation.

Original languageEnglish (US)
Pages (from-to)1343-1347
Number of pages5
JournalJournal of the American Chemical Society
Volume105
Issue number5
DOIs
StatePublished - Mar 1983

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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