Total Syntheses of Cytotoxic, Naturally Occurring Kalasinamide, Geovanine, and Marcanine A

Abstract

Two novel synthetic strategies were developed for the natural products geovanine, marcanine A, and kalasinamide. The nine‐step synthesis of geovanine marks its first total synthesis. The three compounds are known for their antimalarial and antitumor activity, and tests confirmed the high cytotoxity of marcanine A.

Direct Synthesis of Hydroquinones from Quinones through Sequential and Continuous‐Flow Hydrogenation‐Derivatization Using Heterogeneous Au–Pt Nanoparticles as Catalysts

“…Owing to the high reactivity of anthrahydroquinones toward molecular oxygen, hydrogen peroxide is currently produced with the anthraquinone oxidation process; anthraquinone is hydrogenated to generate anthrahydroquinone, which then reacts with molecular oxygen to afford hydrogen peroxide and regenerated anthraquinone –. In other words, isolation of air‐sensitive hydroquinones is very difficult and troublesome, and its derivatization is generally conducted in the presence of stoichiometric amounts of strong reductants without purification of hydroquinone intermediates through a one‐pot procedure combined with reduction of quinones, and applicable derivatization reactions are quite limited –. Hydrogenation using heterogeneous catalysts is one solution; however, overreductions, such as reduction of an aromatic ring or a deoxygenation reaction (which is also a major issue in anthraquinone oxidation processes), are often problematic, especially for hydrogenation of electron‐rich quinones with polycyclic aromatic structures, such as naphthoquinone and anthraquinone –…”

Phosphoric Trichloride

“…9 During the second key step, after optimization, the yield of cyclization and chlorination of a malonic acid amide in presence of POCl 3 is 85%.…”

Investigation on the electrochemistry and cytotoxicity of the natural product marcanine A and its synthetic derivatives

“…1 This natural product possesses remarkable biological activity including antimalarial activity 2 and more importantly, cytotoxicity against various tumor cell lines. 3 Marcanine A 1, together with the related natural products kalasinamide 2 and geovanine 3 belong to the azaanthracenone natural product family (Fig. 1).…”

“…Recently, we and others reported the synthesis of these azaanthracenone natural products and investigated their cytotoxic effect against different cell lines. 3,4 Interestingly, while marcanine A 1 has a strong cytotoxic effect (HeLa, a concentration required to inhibit cell growth by 50% (GI 50 ): 0.75 AE 0.03 mM; Hep, GI 50 : 1.54 AE 0.78 mM), the other two natural products (2 and 3) were totally inactive. 3 The underlying mechanism of the cytotoxic effect of quinones is complex and has been attributed to various events such as redox cycling, mitochondrial dysfunction, 5,6 intercalation into DNA, inhibition of the DNA topoisomerase complex and alkylation via Michael addition.…”

“…We postulate that the cytotoxic properties could be related to the presence of a quinone scaffold, which exists in marcanine A 1 but not in the other, structurally similar natural products (2)(3). In order to investigate the role of the quinone moiety as a relevant scaffold in azaanthracenone natural products, manipulation of the redox potential of the quinone motif was performed to explore the structure-toxicity-relationship with the ultimate aim of designing novel molecules with improved anticancer activity.…”