Synthesis and electrochemistry of annoquinone-A, cypripedin methyl ether, denbinobin and related 1,4-phenanthrenequinones

Abstract

The natural product annoquinone-A (1), the 1,4-phenanthrenequinones 41-75 and the 9,10-dihydro-1,4-phenanthrenequinones 76-81 were prepared by Diels-Alder reaction of the styrenes 23-37 with the benzoquinones 38-40. The sterically hindered 5-methoxy compounds, which adopt a twisted conformation as shown by X-ray analysis, are only formed in trace amounts or as the less hindered 9,10-dihydro-1,4-phenanthrenequinones 76-81. The twisted conformation also leads to characteristic changes in the NMR spectra and the redox potential. Reaction of methoxybenzoquinone with styrenes preferentially affords the 3-methoxy-1,4-phenanthrenequinones. Selective ether cleavage of the 5-methoxy group in 60 leads to the natural product denbinobine (3). Small amounts of C-9 hydroxylated compounds (57, 66, 68, 73, and 75) were also formed in the Diels-Alder reactions. In an alternative synthesis, using the photocylization of the stilbenes 84-87 followed by CAN oxidation, the 1,4-phenanthrenequinones 45, 51, 59 [methyl ether of cyprepidine (2)

Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors

“…The crude product was chromatographed on silica gel and eluted with CH 2 Cl 2 to yield 6b (6.0 mg, 10%). Black solid; mp 215°C [21] ; 1 H NMR (CDCl 3 ): δ 3.93 (s, 3 H), 3.96 (s, 3 H), 6.15 (s, 1 H), 6.82 (d, 1 H, J = 2.8 Hz), 6.93 (d, 1 H, J = 2.8 Hz), 8.06 (d, 1 H, J = 8.8 Hz), 8.12 (d, 1 H, J = 8.8 Hz), 11.00 (s, OH); 13 C NMR (CDCl 3 ): δ 55.5, 56.9, 101.8, 107.3, 108.7, 117.2, 122.6, 128.6, 132.4, 137.4, 139.9, 156.4, 160.8, 161.2, 184.4, 186.5; HRESIMS m/z 307.0584 (calculated for C 16 H 12 O 5 Na, 307.0582).…”

Phenanthrenes: A Promising Group of Plant Secondary Metabolites

“…It is assumed that phenanthroquinones are oxidative derivatives of phenanthrenes or dihydrophenanthrenes, but details of the biosynthesis of these compounds are not fully understood. Oxygenated phenanthrenes and abietane-type diterpenoids can provide the analogous phenanthrenequinones and alkylated 1,4-phenanthrenequinones, respectively. , …”

“…The direct method was a Diels–Alder reaction of styrenes and benzoquinones that led to the substituted phenanthrenequinones or the corresponding dihydro compounds. In the second method, oxygenated phenanthrenes were oxidized to the corresponding quinones . Later, the Kraus group synthesized denbinobin in seven steps from a quinone, substituted with methoxy groups with the correct regiochemistry .…”

Total Synthesis of Tanshinone I

“…16 Experimentally, the determination of the regioselectivity of substitution (C-2 vs C-3) of the benzoquinone ring is challenging due to the similarity of the chemical shifts in the two regioisomers in both the 1 H and 13 C NMR spectra. 17 In 1971, Kakisawa and Inouye proved that the Diels−Alder reaction between 2-methoxy-1,4-benzoquinone and styrene produced compound 10. 16 In 1986, Krohn and Loock determined the structure of 3,8-dimethoxy-1,4-phenanthrenedione (11), synthesized via the Diels−Alder reaction between 2-methoxystyrene and 2-methoxy-1,4-benzoquinone (6) by Xray analysis.…”

“…In practice, the addition to substituted 1,4-benzoquinones occurs only at the unsubstituted double bond . Experimentally, the determination of the regioselectivity of substitution (C-2 vs C-3) of the benzoquinone ring is challenging due to the similarity of the chemical shifts in the two regioisomers in both the 1 H and 13 C NMR spectra . In 1971, Kakisawa and Inouye proved that the Diels–Alder reaction between 2-methoxy-1,4-benzoquinone and styrene produced compound 10 .…”