Philippe Moussou

Microbiological transformations. Part 39: Determination of the regioselectivity occurring during oxirane ring opening by epoxide hydrolases: a theoretical analysis and a new method for its determination

Abstract In the course of this work we have devised new equations as well as a new method allowing for the total determination of the regioselectivity occurring during biohydrolysis of a racemic epoxide by an epoxide hydrolase. This determination is achievable by simply studying the racemic epoxide as a substrate. The results showed that, depending on the enantioselectivity (E value) and the regioselectivity involved, the absolute configuration as well as the enantiopurity of the residual epoxide and of the formed diol appear to be highly variable. For a specific enzyme/substrate couple, the yield and enantiopurity of the less reactive (remaining) epoxide—and thus the possibility to prepare it in enantiopure form—exclusively depend upon the enzyme enantioselectivity. On the other hand, the ee of the formed diol (eep) depends upon the enantioselectivity and on the regioselectivity of the oxirane ring opening. A theoretical analysis based on the material balance, as well as several practical examples, are provided to illustrate the various possibilities of such biohydrolyses.

Microbiological transformations 40. Use of fungal epoxide hydrolases for the synthesis of enantiopure alkyl epoxides

Abstract The enantioselective biohydrolyses of various substituted alkyl-epoxides using seven different fungi are described. These strains were used to achieve the preparation of these alkyl epoxides in high enantiomeric purity. A combined chemoenzymatic process is also described, allowing to enhance the overall yield of such an approach.

Microbiological transformations 41.: Screening for novel fungal epoxide hydrolases

Abstract A search for new fungal epoxide hydrolases is described, which led to the selection of seven strains of interest. The biohydrolyses of various alkyl and aryl epoxides using whole cells of these seven strains are described. The enantio- and regio-selectivity observed proved to be variable depending upon the type of fungus and the substrate structure. However, a general trend was the preferential formation of the diol with ( R ) absolute configuration at the carbon atom bearing the bulkier substituent.

Determination of the regioselectivity during epoxide hydrolase oxirane ring opening: a new method from racemic epoxides

Abstract We describe here a new method for the determination of the regioselectivity of the oxirane ring opening involved in the Epoxide Hydrolase (EH) catalysed hydrolysis of epoxides, simply by starting from the racemic epoxide as a substrate. This method also allows to simultaneously determine the E ratio according to Sihs equation, whose applicability in this context is discussed. This approach affords a complete characterization of the biocatalysed epoxide opening, where three different stereochemical behaviours may be distinguished.