Application of Alcohol Dehydrogenases in Chemoenzymatic Tandem Processes Starting from α,α-Dihalogenated Acetophenones

KINGA KEDZIORA; FABRICIO R. BISOGNO; BARBARA GRISCHEK; IVÁN LAVANDERA; VICENTE GOTOR-FERNÁNDEZ; WOLFGANG KROUTIL; VICENTE GOTOR

SICILIA

Conferencia; BIOTRANS 2011; 2011

BIOTRANS

To gain access to valuable chiral intermediates in the most convenient way possible, a constant effort for developing new asymmetric methodologies that would meet the demanding criteria regarding green chemistry and atom economy is being made. Thus, chemoenzymatic cascade/tandem reactions that avoid the isolation of intermediates, perfectly fit into the requirements of the industrial sector. 1 In this area, the use of alcohol dehydrogenases (ADHs) represents an elegant approach to obtain enantiopure alcohols and if used with highly reactive dihalogenated compounds, the scope of potential intermediates can become significant. Encouraged by previous results obtained in our research group applied to the bioreduction of α-halogenated ketones, 2 we have decided to extend our studies synthesizing and reducing α,α-dihalogenated acetophenone derivatives by means of available ADHs (Figure 1).Figure 1. Bioreduction of α,α-dihalogenated ketones and possible chemical applications of the α,α-dihaloalcohols obtained.Results obtained so far indicate not only excellent conversion and stereoselectivity for the bioreduction of bulky ketones but also remarkable diastereoselectivities in the production of α-bromo-α-chloro alcohols. Furthermore, an oxidation study with the so-obtained α,α-dihalo alcohols is currently being developed to achieve the corresponding mandelic acid derivatives in a chemoenzymatic tandem process.