Development of a Novel Synthetic Route to optically Active Anthracyclinones : Preliminary Synthesis of the Racemic Key Intermediate

抄録

In order to develop a novel synthetic route to a key synthetic intermediate ((R)-(-)-3) for optically active anthracyclinones (2a-d), preparation of the racemic intermediate ((±)-3) from the α, β-unsaturated ketone (6), obtainable from the α, β-unsaturated acid (5) or the 2-tetralone (11), was attempted according to the designed synthetic scheme. Since epoxidation of the racemic allylic alcohol ((±)-7) produced by reduction of 6, followed by reductive cleavage of the epoxides ((±)-8a, b) and oxidation of the vicinal-diol ((±)-9a), was found to readily give the desired (±)-3 in good overall yield, optically pure (R)-(-)-3 should be obtainable from 6 if 6 can be asymmetrically reduced to afford (S)-7 in a high optical yield. The racemic ketone ((±)-3) was further transformed to (±)-7-deoxy-4-demethoxy-daunomycinone dimethyl ether ((±)-13), from which racemic 4-demethoxyanthracyclinone ((±)-2c, d) could be elaborated.