The selective addition of water to CC bonds; enzymes are the best chemists

Abstract

Water is the liquid of life. Nature has therefore evolved countless enzymes that catalyse the addition of water to C=C bonds, isolated or conjugated. These reactions are regio- and enantioselective, they are part of primary metabolism as well as the secondary metabolism. The enzymes that catalyse these reactions (hydratases or hydro-lyases) are applied industrially in selected cases. However, they are not generally used in the laboratory although they outperform all currently available catalytic chemical methodologies. This feature article highlights the potential that hydratases have for chemistry compared to the acid catalysed addition of water.

Enantioselective preparation of (R) and (S)-3-hydroxycyclopentanone by kinetic resolution

“…Here a straightforward approach to this valuable building block for amongst others the Prostaglandins' is described [9,10]. Moreover 3-hydroxycyclopentanone is a valuable compound for the study of enantioselective Michael addition reactions of water [11][12][13].…”

Enhancing the Pharmacokinetic Properties of Botulinum Neurotoxin Serotype A Protease Inhibitors through Rational Design

“…First, the highly hydrophobic 2,4-dichlorophenyl ring both compromises the solubility of the compound and also is unable to take advantage of potential hydrophilic interactions in the active site of the enzyme. The cinnamate provides a second liability of the structure, as this moiety can undergo possibly deleterious Michael addition 16 making 1 potentially unstable in vivo .…”

Michael hydratase alcohol dehydrogenase or just alcohol dehydrogenase?

“…The large subunit contains a molybdopterin, the medium subunit a FAD and the small subunit a [2Fe-2S] cluster (Jin and Hanefeld [2011]). This particular enzyme architecture is also found in the molybdenum-containing hydroxylase family.…”

“…In contrast to the low number of chemical methods, nature is capable of performing this reaction and many examples have been described (Jin and Hanefeld [2011]). The beauty of this reaction is obvious: Using water as a nucleophile and solvent would allow a green route to hydroxy ketones.…”