Alcohols with ADH

The ADH from Lactobacillus brevis (Riebel, 1997) has a broad substrate specificity and converts even bulky aromatic ketones with high activity (Hummel, 1999 Wolberg, 2001). In addition, the enzyme is the best characterized completely (R)-specific ADH. The enzyme belongs to the class of short-chain dehydrogenases and its 3D structure has recently been solved (Niefind, 2003). The recombinant form of L. brevis ADH in E. coli accepts a variety of /j.d-dikelo esters as was determined in the synthesis of potential building blocks for HMG CoA reductase inhibitors (see also Chapter 13, Section 13.3.2) (Wolberg, 2001). tert-Butyl 3,5-dioxohexanoate and tert-butyl 3,5-dioxoheptanoate were reduced on a preparative scale to afford the corresponding (R)- 5-hydroxy-/3-keto esters with 99.4% e.e. and 98.1% e.e., respectively. 

A similar compound, tert-butyl 6-chloro-3,5-dihydroxyhexanoate, was synthesized via the key step of a highly regio- and enantioselective single-site reduction of tert-butyl 6-chloro-3,5-dioxohexanoate by two enantiocomplementary biocatalysts  

Both biotransformations were performed on a gram scale. The /3-keto group of the enantiomeric S-hydroxy-/3-keto esters thus obtained was reduced by syn- and anti-selective borohydride reductions (see Section 13.3.2). 

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Methods to produce chiral alcohols with ADHs are essentially described at a laboratory scale, namely those using HLADH, TBADH and the recently isolated enzymes from Rhodococcus erythropolis, and Lactobacillus kefir and L. brevis, respectively. 

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