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 a nd the 9,10-dihydro-1,4-phenanthrenequinones 76-81 were prepared by Diels-A lder reaction of the styrenes 23-37 with the benzoquinones 38-40. The steri cally hindered 5-methoxy compounds, which adopt a twisted conformation as s hown by X-ray analysis, are only formed in trace amounts or as the less hin dered 9,10-dihydro-1,4-phenanthrenequinones 76-81. The twisted conformation also leads to characteristic changes in the NMR spectra and the redox pote ntial. 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 amo unts of C-9 hydroxylated compounds (57, 66, 68, 73, and 75) were also forme d in the Diels-Alder reactions. In an alternative synthesis, using the phot ocylization of the stilbenes 84-87 followed by CAN oxidation, the 1,4-phena nthrenequinones 45, 51, 59 [methyl ether of cyprepidine (2)], 92 and the 1, 2-phenanthrenequinone 93 were prepared. The Thiele-Winter reaction of 41, 5 5, and 56 yields mixtures of ca. 1:1 oxygenation at C-2 and C-3, thus compl ementing the Diels-Alder reaction in the preparation of 2-methoxy-1,4-phena nthrenequinones. The 1,4-phenanthrenequinones 46, 54, 67 are easily epoxidi zed with alkaline hydroperoxide to 102-104 in analogy to 1,4-naphthoquinone s.