Total Synthesis of Actinorhodin

Abstract

The enantioselective total synthesis of actinorhodin (1) is described. The synthesis features 1) dual benzyne reactions en route to the monomer, 2) the trans‐selective installation of the side chain, and 3) a regioselective oxidative dimerization.

Study on Integrated Synthesis of Dimeric Pyranonaphthoquinones: Preparation of Versatile Synthetic Intermediate and Conversion into ent-Hemi-actinorhodin and ent-Hemi-γ-actinorhodin

“…11 However, attempts at chemical dimerization of 8 failed, 12 suggesting need of judicious substrate design and/or choice of the reaction conditions. 1c 6 13 Fortunately, we discovered that compound C having three oxy functions at C6, C9, C10 nicely dimerized under Laatsch conditions. 13 Aided by the free C9 phenol, the dimerization proceeded regioselectively at C8–C8′ positions.…”

Modular Metal‐Quinone Networks with Tunable Architecture and Functionality

“…Streptonigrin and β‐lapachone are already being used as experimental drugs owing to their various pharmacophores and electron transport chains involved in cellular metabolism [33–35] . The quinones were chosen to contain 1,8‐naphthoquinone moieties because of: (i) the similar distance between oxygen atoms (0.26 nm) to that of catechol moieties (0.27 nm) for the generation of hydrogen bonding, coordination, and other interactions with substrates and the environment (Figure 1a); (ii) their weaker affinity to metal ions (stability constant for Fe 3+ is log K 1 ≈11 vs log K 1 ≈20 for catechol moieties) [36, 37] that allows the coordination (i.e., metal‐acetylacetone) bonds to respond to stimuli (e.g., pH) (Figure 1a); and (iii) their diverse functionalities in biology and electrochemistry owing to their active pharmacophores and electron transport chains [33–35] . Specifically, five quinone ligands (naphthazarin (NZ), shikonin (SK), quinizarin (QZ), anthrarufin (AR), and DOX) and nine metal ions (Al 3+ , Fe 2+ , Fe 3+ , Co 2+ , Ni 2+ , Cu 2+ , Zr 4+ , Pd 2+ , and Eu 3+ ) were used to create a library of metal‐quinone networks (MQNs), including particles, tubes, capsules, and films, in solution and/or on various organic and inorganic substrates (Figure 1a,b).…”

Modular Metal‐Quinone Networks with Tunable Architecture and Functionality

“…Furthermore, natural quinone compounds, such as cribrostatin, streptonigrin, and β‐lapachone, are being studied for their anticancer activities. Streptonigrin and β‐lapachone are already being used as experimental drugs owing to their various pharmacophores and electron transport chains involved in cellular metabolism [33–35] . The quinones were chosen to contain 1,8‐naphthoquinone moieties because of: (i) the similar distance between oxygen atoms (0.26 nm) to that of catechol moieties (0.27 nm) for the generation of hydrogen bonding, coordination, and other interactions with substrates and the environment (Figure 1a); (ii) their weaker affinity to metal ions (stability constant for Fe 3+ is log K 1 ≈11 vs log K 1 ≈20 for catechol moieties) [36, 37] that allows the coordination (i.e., metal‐acetylacetone) bonds to respond to stimuli (e.g., pH) (Figure 1a); and (iii) their diverse functionalities in biology and electrochemistry owing to their active pharmacophores and electron transport chains [33–35] .…”

“…[33][34][35] The quinones were chosen to contain 1,8naphthoquinone moieties because of: (i) the similar distance between oxygen atoms (0.26 nm) to that of catechol moieties (0.27 nm) for the generation of hydrogen bonding, coordination, and other interactions with substrates and the environment (Figure 1a); (ii) their weaker affinity to metal ions (stability constant for Fe 3 + is log K 1 � 11 vs log K 1 � 20 for catechol moieties) [36,37] that allows the coordination (i.e., metal-acetylacetone) bonds to respond to stimuli (e.g., pH) (Figure 1a); and (iii) their diverse functionalities in biology and electrochemistry owing to their active pharmacophores and electron transport chains. [33][34][35] Specifically, five quinone ligands (naphthazarin (NZ), shikonin (SK), quinizarin (QZ), anthrarufin (AR), and DOX) and nine metal ions (Al 3 + , Fe 2 + , Fe 3 + , Co 2 + , Ni 2 + , Cu 2 + , Zr 4 + , Pd 2 + , and Eu 3 + ) were used to create a library of metal-quinone networks (MQNs), including particles, tubes, capsules, and films, in solution and/or on various organic and inorganic substrates (Figure 1a,b). The MQNs were readily post-functionalized with synthetic molecules (e.g., PEG), small natural molecules (e.g., tannic acid (TA) and carboxymethyl chitosan (CCH)), and proteins (e.g., trypsin and catalase).…”