Dibenzocyclooctadiene lignans

The pharmaceutically very interesting dibenzocyclooctadiene lignans, such as steganacin, steganone and schizandrin8-10, constitute ideal synthetic substrates for this method since they have the required oxygenation pattern. 

The application of the Ullmann coupling to the synthesis of dibenzocyclooctadiene lignans was described in the late 1970 s by the groups of Ziegler and of Brown and Robin. 

Natural products 130-140 are dibenzocyclooctadiene lignans (Figure 9-8). Structurally, they contain a linked biphenyl or phenyl/ketocyclohexadiene system, which can have either an S- (130-136) or R-configuration (137-140). Each ring is substimted at positions 1, 2, 3 and 12, 13, 14 with combinations of methoxy, methylenedioxy, or hydroxy groups. Four carbons C-6 C-9 and the biphenyl link-... 

TABLE 9-7. Anti-HIV Activities of Potent Dibenzocyclooctadiene Lignans and Biphenyl Derivatives ... 

Dibromination of Dibenzocyclooctadiene Lignans Five dibrominated derivatives (142-146, Figure 9-8) were synthesized from compounds 132 and 137-140, and evaluated for anti-HIV activity. Only 143 had an ECso lower than 10 pM (EC50 = 7.2 pM and TI = 5) however, it was still less potent than its parent compound 137 (EC50 = 2.0 pM and TI = 56, Table 9-7). 

Isoschizandrin 15 represents one of nearly forty dibenzocyclooctadiene lignans isolated from the fruit of Schizandra chinensis, a creeping vine native to northern China. The extracts from this lignan-rich plant have been used in both Chinese and Japanese traditional medicine as an antitussive, and several lignans isolated from these extracts are thought to exhibit antirheumatic and antihepatotoxic... 

This reaction was a key step in the synthesis of the (+)-form of the dibenzocyclooctadiene lignan lactone steganacin (5).°... 

Li L, Xue H, Tan R 1985 Dibenzocyclooctadiene lignans from roots and stems of Kadsura coc-cinea. Planta Med 297-300... 

Molander s research group employed an 8-endo-trig car-bonyl-alkene cyclization for the final step of their total synthesis of isoschizandrin, a dibenzocyclooctadiene lignan isolated from the fruit of Schizandra chinesis, a creeping vine native to northern China. The final intermediate, optically active biaryl compound 129 was treated with Sml2 in the presence of rBuOH and HMPA to provide isoschizandrin (130) in 85% yield as a >18 1 mixture of diastereo-mers (Scheme 25.62). 

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