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

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)], 92 and the 1,2-phenanthrenequinone 93 were prepared. The Thiele-Winter reaction of 41, 55, and 56 yields mixtures of ca. 1:1 oxygenation at C-2 and C-3, thus complementing the Diels-Alder reaction in the preparation of 2-methoxy-1,4-phenanthrenequinones. The 1,4-phenanthrenequinones 46, 54, 67 are easily epoxidized with alkaline hydroperoxide to 102-104 in analogy to 1,4-naphthoquinones.