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.
ASJC Scopus subject areas
- Colloid and Surface Chemistry