Regioselective oxidative phenol couplings of 2,3′,4,6-tetrahydroxybenzophenone in cell cultures of Centaurium erythraea RAFN and Hypericum androsaemum L.

Abstract

A crucial step in plant xanthone biosynthesis is the cyclization of an intermediate benzophenone to a xanthone. In cultured cells of Centaurium erythraea RAFN, 2,3¢,4,6-tetrahydroxybenzophenone (THBP) was shown to be intramolecularly coupled to 1,3,5-trihydroxyxanthone, whereas in cell cultures of Hypericum androsaemum L. it was coupled to form the isomeric 1,3,7-trihydroxyxanthone. These regioselective cyclizations that occur ortho and para, respectively, to the 3¢-hydroxy group of the benzophenone depend on cytochrome 450 , as shown by the eectiveness of established 450 inhibitors and blue-light-reversible carbon monoxide inhibition. Furthermore, the reactions absolutely require NADPH and O 2 . The underlying reaction mechanism is probably an oxidative phenol coupling that is catalyzed regioselectively by xanthone synthases. These enzymes are proposed to be cytochrome 450 oxidases. The intramolecular cyclizations of THBP to 1,3,5-and 1,3,7-trihydroxyxanthones catalyzed by the two xanthone synthases represent an important branch point in the plant xanthone biosynthetic pathway.Abbreviations: HMBC = heteronuclear multiple-bond connectivity; HMQC = heteronuclear multiple-quantum coherence; NMR = nuclear magnetic resonance; THBP = 2,3¢,4,6-tetrahydroxybenzophenone

Naturally Occurring Xanthones: Chemistry and Biology

“…Conversely, feeding of 14 C-labeled acetate gave incorporation of the main part in the A-ring. The alternative ring closure to (1) has recently been shown to take place in cultured cells of Centaurium erythraea, where 2,3 ,4,6-tetrahydroxybenzophenone Journal of Applied Chemistry is the precursor for 1,3,5-trihydroxyxanthone [128]. Furthermore, in these cell cultures, compound (1) is selectively oxidized by a xanthone 6-hydroxylase to 1,3,5,6-tetrahydroxyxanthone [129].…”

Chemotaxonomy and pharmacology of Gentianaceae

“…The alternative ring-closure to 8 has recently been shown to take place in cultured cells of Centaurium erythraea, where 2,3′,4,6-tetrahydroxybenzophenone is the precursor for 1,3,5-trihydroxyxanthone (8; Fig. 6.8) (Peters et al, 1998). Furthermore, in these cell cultures compound 8 is selectively oxidized by a xanthone 6-hydroxylase to 1,3,5,6-tetrahydroxyxanthone (Schmidt et al, 2000).…”

Xanthone biosynthesis and accumulation in calli and suspended cells of Hypericum androsaemum

“…Peters et al [21] reported that cell suspension cultures of H. androsaemum accumulate several non-identified xanthones, which, from preliminary spectroscopic data, are prenylated and/or C-glycosylated derivatives of 1,3,6,7-tetrahydroxanthone. According to the same authors, all the xanthones detected in H. androsaemum lack a 5-oxo group.…”

“…Cinnamic acid, benzoic acid, m-hydroxybenzoic acid and malonic acid were found to be efficient precursors of this compound [22]. Beerhues and coworkers [21,23] have studied also the biosynthesis of xanthones in H. androsaemum cell suspensions. Their findings indicate that 3-hydroxybenzoic and benzoic acids are efficient precursors of an intermediate tetrahydroxybenzophenone that is subsequently converted to the xanthone backbone.…”