Enantiopure tertiary alcohols are very valuable building blocks for the synthesis of many different natural products and pharmaceuticals. As a consequence, several chemical and enzymatic strategies to afford such chiral structures have been described. Promising enzymatic approaches with agents such as epoxide hydrolases, dehalogenases and hydroxynitrile lyases have been reported, as well as dihydroxylation by microorganisms. Apart from those valuable options, the hydrolase-based kinetic resolution of tertiary alcohols has been known for the last three decades, as several wild-type enzymes have been reported to be able to accept these sterically hindered molecules. More recently, the existence of an amino acid motif within an enzyme's active site has been identified as highly relevant for the acceptance of such bulky structures. This discovery clearly facilitates the identification of novel biocatalysts for this application. Although several tertiary alcohols have been successfully resolved with wild-type biocatalysts, enantioselectivities have often been too low for synthetic purposes. These limitations have recently been overcome by accessing enzymes from the metagenome through directed evolution or by rational protein design. This minireview describes the state of the art in this area, highlighting aspects of basic academic research into the practical application of biocatalysts for the synthesis of optically active tertiary alcohols.
- Alcohols/*chemistry/*metabolism Animals Catalysis Enzymes/*metabolism Humans Hydroxylation Protein Engineering Stereoisomerism
Kourist, R., Dominguez de Maria, P., & Bornscheuer, U. T. (2008). Enzymatic synthesis of optically active tertiary alcohols: expanding the biocatalysis toolbox. ChemBioChem, 9(4), 491-498. https://doi.org/10.1002/cbic.200700688