Joziknipholones A and B: The First Dimeric Phenylanthraquinones, from the Roots of Bulbine frutescens

Abstract

From the roots of the African plant Bulbine frutescens (Asphodelaceae), two unprecedented novel dimeric phenylanthraquinones, named joziknipholones A and B, possessing axial and centrochirality, were isolated, together with six known compounds. Structural elucidation of the new metabolites was achieved by spectroscopic and chiroptical methods, by reductive cleavage of the central bond between the monomeric phenylanthraquinone and -anthrone portions with sodium dithionite, and by quantum chemical CD calculations. Based on the recently revised absolute axial configuration of the parent phenylanthraquinones, knipholone and knipholone anthrone, the new dimers were attributed to possess the P-configuration (i.e., with the acetyl portions below the anthraquinone plane) at both axes in the case of joziknipholone A, whereas in joziknipholone B, the knipholone part was found to be M-configured. Joziknipholones A and B are active against the chloroquine resistant strain K1 of the malaria pathogen, Plasmodium falciparum, and show moderate activity against murine leukemic lymphoma L5178y cells.

The Assignment of Absolute Stereostructures through Quantum Chemical Circular Dichroism Calculations

“…Nonetheless, there are a few examples, such as those of knipholone anthrone (5) or xylogranatin F (6), for which TDDFT calculations are not sufficient to reproduce the ex- Figure 9. Further selected examples of structurally diverse compounds with different types of stereogenic elements, the absolute configurations of which were established by quantum chemical CD calculations (saludimerin A, [83] ancistrotanzanin A, [84] bi [10]paracyclophanes, [56] joziknipholone A, [85] γ-rubromycin, [86] a Tröger's base derivative, [87] resistoflavin, [88] shearinine D, [89] nigerone; [90] for other examples see ref. [91] ).…”

Antiproliferative and antimalarial anthraquinones of Scutia myrtina from the Madagascar forest

“…Some related anthrone-anthraquinones had selectivities of up to 400 between the chloroquine-sensitive 3D7 strain of P. falciparum and the KB cell line,17 so it is possible that compounds of this class might ultimately be developable as antimalarial agents. This conclusion is supported by the fact that some phenylanthraquinones, including monomeric18,19 and dimeric examples,20 have promising antimalarial bioactivities.…”

Alterporriol-Type Dimers from the Mangrove Endophytic Fungus, Alternaria sp. (SK11), and Their MptpB Inhibitions

“…Moreover, in analogy to known Compounds 4 or 5 , the oxygenated methine group (δ C 61.8 or δ C 72.2) [12,13] was now replaced by a methine group at C-10 (δ C 37.1) in 1 . The moderate upfield-shift of the 10-H signal (δ H 4.73 in 4 or δ H 4.91 in 5 →δ H 4.60 in 1 ) may be ascribed to the deshielding effect of the neighboring tetrahydroanthraquinone system [14,15], thus supporting the northern moiety attached to the aromatic ring of the other moiety via C-10. 2D NMR correlations were used to identify the structure of the southern moiety in 1 , as well.…”

“…The resulting CD was substantially affected by eight chiral centers in the molecular as a consequence of the central C-10-C–2′ axis being able to rotate rather freely in solution, due to low rotational barriers [15]. As shown in Figure 2, several bands between 200 and 400 nm, due to the various π–π* and n–π* transitions of the substituted naphthoquinone chromophore, were observed in the experimental ECD spectrum.…”

“…The novel compound, alterporriol S ( 1 ), was the first member of alterporriols with a unique C-10−C-2′ linkage [20,22,23,26,27,28,29,30,31,32,33]. Anthranoid dimers consisting of such a coupling type could only be found in a small population of terrestrial plants [14,15,34,35,36,37,38,39,40,41,42,43] and marine animal [44]; this was the first report of a fungus origin. In the bioassay, (+)-a S -alterporriol C ( 2 ) showed strong inhibitory activity against MptpB, which indicated that it could represent a new type of lead compounds for the development of new anti-tuberculosis drugs.…”