Total Synthesis of Mycenarubin A, Sanguinolentaquinone and Mycenaflavin B and their Cytotoxic Activities

Abstract

Here we report the first total synthesis of the fungal alkaloids mycenarubin A, sanguinolentaquinone and mycenaflavin B. The pyrroloquinoline alkaloid mycenarubin A was obtained in 10 steps (21 % total yield, 92 % ee) from the known key precursor 6,7‐bis(benzyloxy)indole by an asymmetric alkylation and a biomimetic ring closure as the key steps. The indolo‐6,7‐quinone sanguinolentaquinone was obtained in eight steps (28 % total yield). Mycenaflavin B was also obtained in eight steps starting from the same key precursor (total yield 15 %) by a biomimetic ring closure and an acid‐catalysed decarboxylation reaction as the key steps. The cytotoxic activities of mycenarubin A and mycenaflavin B were evaluated against mouse fibroblasts (L929) and human malignant melanoma cells (RPMI‐7951).

Formaldehyde as a Chemical Defence Agent of Fruiting Bodies of Mycena rosea and its Role in the Generation of the Alkaloid Mycenarubin C

“…We hypothesised that the additional C 1 unit in 2 originated from formaldehyde because formaldehyde could react with the amino group of the side chain in 1 , and thus, form an imine that could be attacked from the nucleophilic ring position at C‐6, forming the eight‐membered ring in 2 . To test this hypothesis, both 1 obtained through total synthesis and that isolated from fruiting bodies of M. rosea were dissolved in two separate experiments in water, and an excess of formalin was added; this resulted in both cases in the quantitative conversion of 1 into 2 . Moreover, the NMR spectroscopy data and CD spectra (Table S3 and Figure S25) of both synthetic and isolated 2 resembled each other very closely, and thus, confirmed the structure and absolute configuration of 2 .…”

“…Mycenarubin A (1) : Red solid; [ α ] =+669 ( c= 0.0055 in H 2 O); HPLC prep : t R =21.8 min; LC‐(+)‐ESIMS: t R =17.24 min; 1 H NMR (900 MHz, D 2 O, 300 K): see Table ; 13 C NMR (226 MHz, D 2 O, 300 K): see Table ; (+)‐ESI‐MS: m / z : 290 [ M +H] + .…”

“…Synthesis of 2 from 1 and formaldehyde : Enantiopure 1 obtained by total synthesis (2.0 mg, 6.9 μmol) was dissolved in H 2 O (1 mL), treated with an excess of formaldehyde (37 % aqueous solution, 5 μL, 69 μmol), and stirred for 2 h at room temperature. The solvent was evaporated and the reaction product was purified on a Sephadex LH20 column with H 2 O as eluent.…”

Aminotenuazonic Acid: Isolation, Structure Elucidation, Total Synthesis and Herbicidal Activity of a New Tetramic Acid from Fruiting Bodies of Laccaria Species

“…Cytotoxicity of aminotenuazonic acid ( 1 a ) (0.07–1.2 m m ) and tenuazonic acid ( 2 ) (0.07–1.3 m m ) was evaluated against mouse fibroblast L929 cells according to the protocol from Backenköhler et al . The cells were incubated for up to 49 h.…”

Structures and Biological Activities of Alkaloids Produced by Mushrooms, a Fungal Subgroup

“…The same article also reported the first isolation of sanguinolentaquinone ( 37 , Figure 3 ), and the identification of decarboxydehydrosanguinone A ( 38 , Figure 3 ) as an oxidative decarboxylation artifact of sanguinone A ( 35 ). The synthesis of 37 was later realized in eight steps and with a 28% total yield [ 39 ].…”