Biocatalysis as a Rational Approach to Enantiodivergent Synthesis of Highly Oxygenated Compounds: (+)- and (-)-Pinitol and Other Cyclitols.

Bacterial oxygenation of halogenated aromatic compounds yields arene cis-diols of type 2 of high enantiomeric purity. Further oxygenation of these extremely versatile synthetic intermediates provides for stereo- and regioselective introduction of additional functionalities such as hydroxyl groups. Several rational methods of oxygenation (epoxidation, osmylation, singlet oxygen addition, and ozonolysis) are used to produce, in short synthetic routes, cyclitol derivatives of medicinal importance. Proper symmetry considerations lead to the development of enantiodivergent synthetic design of target compounds from a single enantiomer of a starting diol. These principles are illustrated on the short syntheses of (+)- and (-)-pinitol. Stereocontrolled oxidative transformation of diols of type 2 are exemplified in the synthesis of conduritol C and dihydroconduritol C. Full experimental details are provided for all compounds. A guide to the stereorational design of any stereoisomer of cyclohexane (poly)ols or carbohydrates is provided at the end of the paper.