TCA Cycle Involved Enzymes SucA and Kgd, as well as MenD: Efficient Biocatalysts for Asymmetric C–C Bond Formation
TL;DR: Asymmetric mixed carboligation reactions of α-ketoglutarate with different aldehydes were explored with the thiamine diphosphate dependent enzymes SucA, Kgd and MenD to selectively deliver chiral δ-hydroxy-γ-keto acids with moderate to excellent stereoselectivity.
About: This article is published in Organic Letters.The article was published on 2013-01-14. It has received 31 citations till now. The article focuses on the topics: Regioselectivity.
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TL;DR: The review provides a guide to the use of biocatalytic methods in the area of chemical synthesis with focused attention on retrosynthetic considerations and analysis and is expected to lead to better understanding of the characteristics and distinctions of the two complementary approaches.
Abstract: Recent developments of stereoselective biocatalytic and chemocatalytic methods are discussed. The review provides a guide to the use of biocatalytic methods in the area of chemical synthesis with focused attention on retrosynthetic considerations and analysis. The transformations presented are organized according to bond disconnections and attendant synthetic methods. The review is expected to lead to better understanding of the characteristics and distinctions of the two complementary approaches. It depicts for researchers in bio- and chemocatalysis a road map of challenges and opportunities for the evolution (and at times revolution) in chemical synthesis.
204 citations
TL;DR: The review gives a selection of biocatalytic C–C-bond-forming reactions which have been investigated during the last 5 years and which have already been proven to be applicable for organic synthesis.
Abstract: Carbon-carbon bond formation is the key reaction for organic synthesis to construct the carbon framework of organic molecules. The review gives a selection of biocatalytic C-C-bond-forming reactions which have been investigated during the last 5 years and which have already been proven to be applicable for organic synthesis. In most cases, the reactions lead to products functionalized at the site of C-C-bond formation (e.g., α-hydroxy ketones, aminoalcohols, diols, 1,4-diketones, etc.) or allow to decorate aromatic and heteroaromatic molecules. Furthermore, examples for cyclization of (non)natural precursors leading to saturated carbocycles are given as well as the stereoselective cyclopropanation of olefins affording cyclopropanes. Although many tools are already available, recent research also makes it clear that nature provides an even broader set of enzymes to perform specific C-C coupling reactions. The possibilities are without limit; however, a big library of variants for different types of reactions is required to have the specific enzyme for a desired specific (stereoselective) reaction at hand.
126 citations
TL;DR: A practical Cu-catalyzed picolinamide-directed o-amination of anilines showing excellent mono-substitution selectivity and high functional group tolerance has been developed.
105 citations
TL;DR: This review covers recent studies and the mechanistic understanding of stereoselective C–C bond forming thiamine diphosphate‐dependent enzymes, which has been guided by structure–function analyses based on mutagenesis studies and from influences of different substrates and organic co‐solvents on stereoselectedivity.
Abstract: Thiamine diphosphate-dependent enzymes are broadly distributed in all organisms, and they catalyse a broad range of C-C bond forming and breaking reactions. Enzymes belonging to the structural families of decarboxylases and transketolases have been particularly well investigated concerning their substrate range, mechanism of stereoselective carboligation and carbolyase reaction. Both structurally different enzyme families differ also in stereoselectivity: enzymes from the decarboxylase family are predominantly R-selective, whereas those from the transketolase family are S-selective. In recent years a key focus of our studies has been on stereoselective benzoin condensation-like 1,2-additions. Meanwhile, several S-selective variants of pyruvate decarboxylase, benzoylformate decarboxylase and 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC) synthase as well as R-selective transketolase variants were created that allow access to a broad range of enantiocomplementary α-hydroxyketones and α,α'-dihydroxyketones. This review covers recent studies and the mechanistic understanding of stereoselective C-C bond forming thiamine diphosphate-dependent enzymes, which has been guided by structure-function analyses based on mutagenesis studies and from influences of different substrates and organic co-solvents on stereoselectivity.
78 citations
TL;DR: This study reviews the hydrolase-catalyzed asymmetric carbon–carbon bond-forming reactions for the preparation of enantiomerically enriched compounds in organic synthesis and reviews the direct asymmetric aldol, Michael, Mannich and Morita–Baylis–Hillman reactions.
Abstract: Enzyme catalytic promiscuity, in which the active site of an enzyme has the ability to catalyze more than one chemical transformation, has received widespread attention as more catalytic promiscuities of existing enzymes have been discovered. In this field, hydrolases have been mainly studied due to their commercial availability, high stability, broad substrate scope and high catalytic efficiency in media containing organic solvents. In this study, we review the hydrolase-catalyzed asymmetric carbon–carbon bond-forming reactions for the preparation of enantiomerically enriched compounds in organic synthesis. To date, these hydrolase-catalyzed asymmetric reactions include the direct asymmetric aldol, Michael, Mannich and Morita–Baylis–Hillman reactions. The hydrolase-catalyzed non-enantioselective examples were not included.
65 citations
References
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TL;DR: Alternative, non-cyclic flux modes occur in leaves in the light, in some developing oilseeds, and under specific physiological circumstances such as anoxia.
665 citations
TL;DR: Emphasis is placed on the development of methods to make laboratory evolution faster and more efficient, thus providing chemists and biotechnologists with a rich and non-ending source of robust and selective catalysts for a variety of useful applications.
Abstract: Asymmetric catalysis plays a key role in modern synthetic organic chemistry, with synthetic catalysts and enzymes being the two available options. During the latter part of the last century the use of enzymes in organic chemistry and biotechnology experienced a period of rapid growth. However, these biocatalysts have traditionally suffered from several limitations, including in many cases limited substrate scope, poor enantioselectivity, insufficient stability, and sometimes product inhibition. During the last 15 years, the genetic technique of directed evolution has been developed to such an extent that all of these long-standing problems can be addressed and solved. It is based on repeated cycles of gene mutagenesis, expression, and screening (or selection). This Review focuses on the directed evolution of enantioselective enzymes, which constitutes a fundamentally new approach to asymmetric catalysis. Emphasis is placed on the development of methods to make laboratory evolution faster and more efficient, thus providing chemists and biotechnologists with a rich and non-ending source of robust and selective catalysts for a variety of useful applications.
468 citations
221 citations
TL;DR: The current view is that the two aromatic rings both contribute to catalysis, perhaps carrying out an intramolecular proton transfer to initiate the various reactions, an ability that makes this coenzyme virtually unique among coenzymes.
210 citations
TL;DR: Thiamin diphosphate‐dependent enzymes participate in numerous biosynthetic pathways and catalyse a broad range of reactions, mainly involving the cleavage and formation of C–C bonds, which extend the synthetic potential for asymmetric carboligations appreciably.
Abstract: Thiamin diphosphate-dependent enzymes participate in numerous biosynthetic pathways and catalyse a broad range of reactions, mainly involving the cleavage and formation of C-C bonds. For example, they catalyse the nonoxidative and oxidative decarboxylation of 2-keto acids, produce 2-hydroxy ketones and transfer activated aldehydes to a variety of acceptors. Moreover, they can also catalyse C-N, C-O and C-S bond formation. Because of their substrate spectra and different stereospecificity, these enzymes extend the synthetic potential for asymmetric carboligations appreciably. Different strategies have been developed to identify new members of this promiscuous enzyme class and the reactions they catalyse. This enabled us to introduce solutions for longstanding synthetic problems, such as asymmetric cross-benzoin condensation. Moreover, through a combination of protein structure analysis, enzyme and substrate engineering, and screening methods we explored additional stereochemical routes that have not been described previously for any of these interesting enzymes.
141 citations