Novel synthesis of optically pure anthracyclinone intermediates by the use of microbial asymmetric reduction with fermenting baker's yeast

Microbial reduction of the racemic α-hydroxy ketones ((±)-3a, b) with fermenting baker's yeast was found to afford diastereomeric mixtures of the vicinal-diols ((-)-4a, b) and ((+)-5a, b) in 90 and 91% yields, respectively. Separation of these diastereomers was readily accomplished by fractional recrystallization, giving pure (-)-4a, b and mixtures of (-)-4a, b and (+)-5a, b. Oxidation of these samples furnished optically pure anthracyclinone intermediates ((R)-(-)-3a, b) and their partially optically active antipodes ((S)-(+)-3a, b). The undesired enantiomers ((S)-(+)-3a, b) and vicinal-diols ((+)-5a, b) could be recycled to (±)-3a, b and the prochiral ketones (6a, c) by racemization with p-toluenesulfonic acid and oxidative cleavage with sodium metaperiodate, respectively. Another important optically pure anthracyclinone intermediate ((R)-(-)-3c) was prepared from (R)-(-)-3a, b according to the reported method.