C2-Ketol elongation by transketolase-catalyzed asymmetric synthesis

The asymmetric synthesis of new carbon-carbon bonds represents a cornerstone of both organic chemistry and biochemistry. Among the variety of synthetic reaction methodologies the aldol and ketol reactions continue to be major technology platforms in the science of synthesis. The efficient utilization of resources and energy towards the synthesis of the product and the reduction of waste are important goals of sustainable chemistry and industrial biotechnology. The transition from stoichiometric to catalytic asymmetric versions of carbon-carbon bond forming reactions is a major topic in various catalysis research areas such as inorganic catalysis, organocatalysis and biocatalysis. alpha-Hydroxyketones are important structural elements in many compounds, but general chemical procedures for asymmetric chain elongation involve several reaction steps with the stoichiometric use of protecting groups. Catalytic methods utilizing transketolases (TKs) as biocatalysts are highly attractive because of their capability of creating new carbon-carbon bonds with high selectivity and broad substrate specificity. The use of hydroxypyruvate makes the chain elongation by two carbon atoms irreversible and provides the practical advantage of changing the reaction thermodynamics from equilibrium to complete conversion. The large-scale production of transketolase and the irreversible C-2-ketol donor beta-hydroxypyruvate have provided the tools to make C-2-ketol elongation attractive for preparative work. The number of reaction steps required for two-carbon extension can thereby be reduced compared with classical chemical synthesis routes. (C) 2009 Elsevier B.V. All rights reserved.