Total Synthesis and Absolute Stereochemistry of the Natural Atropisomer of the Biflavone 4',4"',7,7"-Tetra-O-methylcupressuflavone.

The total synthesis of a natural atropisomer, 4',4"',7,7"-tetra-O-methylcupressuflavone (1), has been achieved. The key intermediate, 3,3'-diacetyl-4,4',6,6'-tetramethoxy-2,2'-biphenyldiol (5), was synthesized by the solid state phenol coupling reaction, and the racemate 5 was enantioresolved as bis(camphanate) esters. The absolute configuration of bis(camphanate) ester (-)-8b was determined to be (aR) by X-ray analysis. The ester (aR)-(-)-8b was converted to the natural biflavone [CD(+)362.0]-(-)-1, leading to the (aR) absolute configuration of 1. This conclusion is consistent with our previous theoretical determination of the absolute stereochemistry of biflavone 1 by the molecular orbital calculation of CD spectra.