The Concept of Docking and Protecting Groups in Biohydroxylation

Abstract

The hydroxylation of unactivated carbon atoms employing methods developed in the realms of classical organic chemistry is difficult to achieve and the processes available lack the degree of chemo-, regio- and enantioselectivity required for organic synthesis. To improve this situation, the concept of docking/protecting groups should enable the organic chemist to employ biohydroxylation as an easy tool for preparative work. Similar to the common practice of using protective groups in organic chemistry, a docking/protecting (d/p) group is introduced first, then the biotransformation is performed, and finally the d/p group is removed. The aim of this concept is not only to avoid time consuming microorganism screening methods, but also to improve hydroxylation position predictability, prevent undesired side reactions, aid substrate detection, and product recovery. This approach is successfully applied to carboxylic acids, ketones, aldehydes, and alcohols.

Improvement of a Stereoselective Biocatalytic Synthesis by Substrate and Enzyme Engineering: 2‐Hydroxy‐(4′‐oxocyclohexyl)acetonitrile as the Model

“…[12] Griengl and co-workers used the docking/protecting concept to direct and enhance the regio-and stereoselectivity of biohydroxylations and to broaden the substrate acceptance of the enzymes involved. [13][14][15] Recently, this approach was also applied to enzyme-catalyzed cyanohydrin reactions. HbHNL (Hb = Hevea brasiliensis, HNL = hydroxynitrile lyase) showed a high increase in enantiopreference toward "thio-disguised" 2-butanone compared with the unmasked ketone.…”

“…Wang and Withers, for example, obtained an increased reaction rate for glycosidases by substrate‐assisted catalysis 12. Griengl and co‐workers used the docking/protecting concept to direct and enhance the regio‐ and stereoselectivity of biohydroxylations and to broaden the substrate acceptance of the enzymes involved 13–15. Recently, this approach was also applied to enzyme‐catalyzed cyanohydrin reactions.…”

Enzymatic synthesis of enantiopure alcohols: current state and perspectives

“…52 The 'docking/protecting' (d/p) group concept has been employed to modify a substrate and thereby improve a given biohydroxylation. 53 This concept was applied for the rst time to increase the stereoselectivity, as exemplied for the hydroxylation of substrate 3d with Beauveria bassiana ATCC 7159 (ref. 54) ( Fig.…”

Controlling substrate specificity and product regio- and stereo-selectivities of P450 enzymes without mutagenesis

“…Early studies with monooxygenases suggested that the presence of specific functional groups can improve substrate acceptance by biocatalysts. [37][38][39][40][41][42][43][44] Substrate engineering may involve the covalent addition of a specific recognition motifs, the chemical auxiliary or directing group, to an unnatural substrate with the aim of facilitating recognition by the enzyme and favoring a specific productive binding orientation (Figure 3). 43,45 …”