A Novel and Highly Efficient Asymmetric Synthesis of Optically Active Anthracyclinones

Abstract
The bromolactonization of the optically active acetals derived from 2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene and (R,R)-N,N:N′,N′-tetraalkyltartaramide was found to proceed highly diastereoselectively, giving mixtures of the seven-membered bromo lactones and the bromohydrins. The predominantly produced bromo lactones could be effectively converted to (R)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol, the AB ring synthon of optically active 11-hydroxyanthracyclinones, >95% ee, in one pot reaction. Application of the explored synthetic scheme to 2-acetyl-5,12-dimethoxy- and 2-acetyl-5-methoxy-3,4-dihydro-6,11-naphthacenedione similarly gave (R)-2-acetyl-2,5,12-trihydroxy- and (R)-2-acetyl-2,5-dihydroxy-1,2,3,4-tetrahydro-6,11-naphthacenedione, the advanced key synthetic intermediates of optically active 4-demethoxy- and 11-deoxy-4-demethoxyanthracyclinones, 94% ee and >99% ee, respectively, by way of mixtures of the seven- and six-membered bromo lactones.

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