Bouvardin and Deoxybouvardin, Antitumor Cyclic Hexapeptides from Bouvardia ternifolia (Rubiaceae)

Bouvardin (C40H48N6O10) and deoxybouvardin (C40H48N6O9), both of which show high antitumor activity in the 3PS, B1, and KB systems, were isolated from the methanol extract of Bouvardia ternifolia (Rubiaceae). An x-ray study on bouvardin containing a methanol of crystallization (P212121, a=9.009 (3), b=12.623 (4), c=42.970 (19) Å, Z=4) and hydrolytic studies showed it to be Ia, a cyclic hexapeptide composed of two L-alanines, a D-alanine, and three modified N-methyl-L-tyrosines. The most unusual feature is a 14-membered ring formed by oxidative coupling of the phenolic oxygen of one tyrosine with a carbon ortho to the phenolic hydroxyl group of an adjacent tyrosine. Spectral comparison with bouvardin indicated deoxybouvardin to be Ib, identical with bouvardin except for the lack of a β-hydroxyl group on one of the tyrosines.