Enzyme-catalyzed regio- and enantioselective ketone reductions

In this chapter, examples are given of the application of highly reactive prochiral ketones as substrates for enzymatic reductions. 3,5-Dioxocarboxylates are polyketide-like compounds that can be used to synthesize all of the possible stereoisomers of the corresponding 1,3-diols by means of regio- and enantioselective enzymatic reduction. The results obtained from an investigation into the usefulness of the resulting hydroxyl ketones and 1,3-diols in organic synthesis led to the development of non-natural functionalized ynones as a starting material for the enzymatic route to enantiopure propargylic alcohols. A broad variety of substituted acetylenic ketones can be reduced enantioselectively by the oxidoreductases Lactobacillus brevis ADH (LBADH), Candida parapsilosis carbonyl reductase (CPCR), horse liver ADH (HLADH) and Thermoanaerobium brockii ADH (TBADH). The resulting propargylic alcohols can be obtained in either enantiomeric form, since (R)- and (S)-specific oxidoreductases can be applied. By varying the size of the substituents, the enantiomeric excess can be tuned, or the enantioselectivity can even be reversed. The obtained highly functionalized enantiopure alcohols are synthetically flexible chiral building blocks that offer new synthetic strategies for target- and diversity-oriented synthesis.