Dynamic Kinetic Resolution of Amines Involving Biocatalysis and in Situ Free Radical Mediated Racemization

Gastaldi, Stéphane; Escoubet, Stéphanie; Vanthuyne, Nicolas; Gil, G.; Bertrand, M.

doi:10.1021/ol063062o

Cited by 94 publications

(47 citation statements)

References 15 publications

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“…reported. 267 Immobilised lipase-catalysed DKR yielding optically active cyanohydrin acetates were obtained in good yields and up to 93 % e.e. employing the use of a silica-supported ammonium hydroxide as the racemisation catalysts (Scheme 12).…”

Section: Scheme 11mentioning

confidence: 99%

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

Milner¹,

Maguire²

2012

Arkivoc

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Modern synthetic organic chemistry has experienced an enormous growth in biocatalytic methodologies; enzymatic transformations and whole cell bioconversions have become generally accepted synthetic tools for asymmetric synthesis. This review details an overview of the latest achievements in biocatalytic methodologies for the synthesis of enantiopure compounds with a particular focus on chemoenzymatic synthesis in non-aqueous media, immobilisation technology and dynamic kinetic resolution. Furthermore, recent advances in ketoreductase technology and their applications are also presented.Keywords: Biocatalysis, kinetic and dynamic kinetic resolution, Baker's yeast, ketoreductases General IntroductionAsymmetric synthesis is the preferential formation of one stereoisomer of a chiral target compound to another; when scientists at GlaxoSmithKline, AstraZeneca and Pfizer 1 examined 128 syntheses from their companies, they found as many as half of the drug compounds made by their process research and development groups are not only chiral but also contain an average of two chiral centres each. 2In 2006 just 25 % were derived from the chiral pool and over 50 % employed chiral technologies. 1In order to meet regulatory requirements enantiomeric purities of 99.5 % were deemed necessary by the FDA. 3 This is one of the biggest challenges which face chemists today, primarily due to the recognition of the fact that different enantiomers of the same compound can interact differently in biological systems. As a consequence, the production of single enantiomers instead of racemic mixtures has become an important process in the pharmaceutical and agrochemical industry. Several routes can lead to the desired enantiomer including transition metal-, [4][5][6] organo-5,7-10 and bio-catalysis [11][12][13][14][15] and these have been thoroughly reviewed in the literature. 16,17 2. Biocatalysis IntroductionBiocatalysis involves the use of enzymes or whole cells (containing the desired enzyme or enzyme system) as catalysts for chemical reactions. A timeline of historic events in biocatalysis and biotechnology is outlined in Table 1. [18][19][20] Reviews and Accounts Novel methodologies for discovering industrial enzymes based on genomic sequencing and phage display (discussed further in Section 1.3), 21,22 as well as highly effective optimisation tools based on chemical, physical and molecular biology approaches, 23 have improved the access to biocatalysts, increased their stability, and radically broadened their specificity. 24This greater availability of catalysts with superior qualities including the use of new bioengineering tools contributed significantly to the development of new industrial processes. Biocatalytic methodologies for organic synthesis were outlined by Woodley et al. in three categories: established, emerging and expanding chemistries as depicted in Figure 1. 25 Enzyme classesBy the late 1950s it had become evident that the nomenclature of enzymes without any guiding authority, in a period when the...

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Section: Scheme 11mentioning

confidence: 99%

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

Milner¹,

Maguire²

2012

Arkivoc

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“…Combination with CAL-B enabled the DKR of nonbenzylic amines 59 yielding amides (R)-60 in good yield and high enantioselectivities [44].…”

Section: Dkr Using Hydrolytic Enzymes and Racemization Catalystsmentioning

confidence: 99%

“…44 Removal of pyruvate using pyruvate decarboxylase.452j 14 Biocatalytic Routes to Nonracemic Chiral Amines synthesis of enantiomerically pure amines from their corresponding ketones using D-or L-alanine as the amine donor and lactate dehydrogenase to drive the reaction equilibrium via the removal of the coproduct pyruvate. Excellent enantioselectivities (>99% in many cases) were achieved for each enantiomer of amine product (Figure 14.45).…”

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confidence: 99%

Biocatalytic Routes to Nonracemic Chiral Amines

Turner

Truppo

2010

Chiral Amine Synthesis

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Enantiomerically pure chiral amines are highly valuable functionalized molecules with a wide range of applications including (i) intermediates for the synthesis of pharmaceutical and agrochemical active ingredients, (ii) resolving agents for the separation of enantiomers via diastereomeric salt formation, and (iii) ligands for asymmetric synthesis using either transition metal catalysis or organocatalysis [1]. The option of preparing chiral amines using biocatalytic approaches is now viewed as attractive as a result of recent developments in biocatalyst availability, methods for improving biocatalyst stability, and the inherent high selectivity and catalytic activity that can be obtained through enzyme catalysis. This chapter reviews the methods that are currently available for the preparation of chiral amines using biocatalysis. The review focuses on those biocatalytic methods in which the amine functionality is involved directly in the biocatalytic transformation (e.g., the synthesis of amino alcohols in which the alcohol functionality is manipulated by lipase-catalyzed acylation or hydrolysis are omitted). In addition, biocatalytic methods for the preparation of amino acids are also outside the scope of this review. The chapter is organized according to the three general approaches that have been developed, namely, kinetic resolution (KR), dynamic kinetic resolution (DKR) and deracemization, and finally asymmetric synthesis. A final section deals with emerging approaches including the use of imine reductases. As summarized in Figure 14.1, using a-methylbenzylamine 1 as a model compound, each of the methods discussed in this chapter possesses advantages and disadvantages in terms of (i) availability of starting material, (ii) efficiency of the process (i.e., kinetic resolution versus asymmetric synthesis), (iii) range of chiral amines that can be prepared (1 , 2 , 3 ), (iv) availability of biocatalyst, and (v) possible requirement for cofactor recycling. Each of these issues is dealt with throughout the chapter. Table 14.1 provides details of commercial sources of the enzymes referred to in the text.

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“…These catalysts were able to racemize various primary and secondary aromatic amines and were also compatible with the enzymatic resolution [42,43]. An alternative approach to metal-catalyzed racemization via imine formation is the racemization catalyzed by alkylsulfanyl radicals [44,45]. The combination of these racemization catalysts with a protease resulted in the first synthesis of an (S)-amide via DKR as an alternative to most other DKR processes that produce the (R)-amides [44,45].…”

Section: Homogeneous Catalysts For Racemization and Dkr Of Chiral Aminesmentioning

confidence: 99%

Heterogeneous Catalysts for Racemization and Dynamic Kinetic Resolution of Amines and Secondary Alcohols

et al. 2010

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This paper gives an overview of the available heterogeneous catalysts for racemization of chirally stable secondary alcohols and amines, and of the combination of these catalysts with immobilized enzymes in dynamic kinetic resolution (DKR) for production of enantiopure esters or amides. For the one-pot DKR process, compatibility of enzyme and heterogeneous catalyst is a major issue, and in some cases the combination fails because of (mutual) deactivation. Heterogeneous catalysts of various types, such as zeolites or oxides effect alcohol racemization; they function either via acid catalysis and carbenium chemistry, or via a redox pathway via the ketone. Dynamic kinetic resolution of aliphatic alcohols using a heterogeneous catalyst in mild conditions is however an open challenge. Heterogeneous amine racemization catalysts invariably operate using a redox mechanism via the imine. In this case, the scope encompasses benzylic and aliphatic amines. The practicality of the approach is illustrated with the production of enantiopure N-acylated homoserine lactones, which are signalling compounds in microbial communities.

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Dynamic Kinetic Resolution of Amines Involving Biocatalysis and in Situ Free Radical Mediated Racemization

Cited by 94 publications

References 15 publications

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

Biocatalytic Routes to Nonracemic Chiral Amines

Heterogeneous Catalysts for Racemization and Dynamic Kinetic Resolution of Amines and Secondary Alcohols

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