Recent progress in stereoselective synthesis with aldolases

Aldol reactions constitute a powerful methodology for carbon–carbon bond formation in synthetic organic chemistry. Biocatalysis by means of aldolases offers a unique stereoselective and green tool to perform this transformation. Recent advances in the field, fueled by either protein engineering or screening, greatly improved the number of synthetic opportunities from small chiral polyfunctional molecules to highly complex oligosaccharide analogs with potential pharmaceutical relevance. Furthermore, aldolases have been shown to be particularly valuable for obtaining new types of structures (i.e. generate molecular diversity) accessible for investigations in drug discovery. Extensive knowledge arising from biochemical studies and synthetic applications of natural aldolases has fostered the development of novel catalysts, such as the de novo computational design of aldolase enzymes, aldolase ribozymes, or synthetic peptides and foldamers with aldolase activity, outlining first steps toward the creation of tailor-made (bio)catalysts to suit any desired application.This work was supported by the Spanish MCINN CTQ2006-01345/BQU, Generalitat de Catalunya DURSI 2005-SGR-00698. AS/GS and WDF were supported by the DFG through SPP1170 (Sp503/4-2 and Fe244/7-2, respectively). The authors especially acknowledge the financial support from ESF project COST CM0701, which has provided a valuable opportunity for knowledge exchange between the research groups.Peer reviewe