Enzymatic hydroxylation of arene and symmetry considerations in efficient synthetic design of oxygenated natural products

Microbial oxidation of substituted aromatic compounds with mutant strains of Pseudomonas puridu (39D) yields the corresponding arene cis-diols in efficient quantities and >99% ee. The use of these synthons in the practical preparation of oxygenated naturalproducts is described with emphasis on the importance of symmetry considerations during synthetic planning in order to achieve enantiodivergent preparations of target compounds. The applications are highlighted by discussion of the syntheses of the following compounds from chlorobenzene : (+)- and (-)- erythrose, (+)- and (-)- ribonolactone, (+) - and (-)-trihydroxyheliotridane, (+)- and (-)-pinitol, kifunensine, lycoricidine and a model study for a short synthesis of (-)-morphine. The conclusion of the lecture places in perspective the use of halogenated aromatics in the chiral pool supply with the potential of efficiently replacing sugars. Brevity and efficiency of the synthetic sequences are emphasized.