Synthesis of a variety of optically active hydroxylated heterocyclic compounds using epoxide hydrolase technology

Pienaar, Daniel P.; Mitra, Robin; Deventer, Thomas I. van; Botes, Adriana L.

doi:10.1016/j.tetlet.2008.08.097

Cited by 13 publications

(11 citation statements)

References 25 publications

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“…An amide-nitrogen participated intramolecular S N 2 epoxide ring-opening of 9 [12] was then projected to bring up the γ-lactam framework. Further deduction from γ,δ-epoxy-amide (9) clearly suggested the intermediacy of acid 11.…”

Section: Methodsmentioning

confidence: 99%

Novel Concise Synthesis of (−)‐Clausenamide

Liu¹,

Yu²,

Huang³

2013

Chin. J. Chem.

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A six-step synthesis of (−)-clausenamide is described. Optically pure (R,E)-1,3-diphenylallylic alcohol was acetylated and then subjected to an Ireland-Claisen rearrangement, giving the γ,δ-unsaturated acid, which underwent a substrate-induced stereoselective bromolactonization to afford the expected all-equatorial substituted bromo-δ-lactone. An unusual chemo-selective aminolysis of the lactone resulted in the formation of a γ,δ-epoxy-amide in stereospecific manner. Base-promoted cyclization of this intermediate and the subsequent Davis oxidation furnished the synthesis, delivering the final product in ＞99% ee and up to 34% overall yield.

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Section: Methodsmentioning

confidence: 99%

Novel Concise Synthesis of (−)‐Clausenamide

Liu¹,

Yu²,

Huang³

2013

Chin. J. Chem.

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“…An indirect biocatalyzed methodology for producing (S)-103 was described by Pienaar et al (2008), using a chemoenzymatic approach also presented in Figure 33. Hence, the racaemic epoxide 106 was opened using whole cells of Yarrowia lipolytica containing epoxide hydrolase activity, and the nonconverted substrate (S)-106 (20% yield, 97.8% ee) was chemically opened leading to halohydrin (S)-108, which upon a lipase-catalyzed hydrolysis and acid catalysis furnished (S)-103 with moderate yields (79%), not altering the good enantioselectivity obtained in the preparation of starting (S)-106.…”

Section: Sodium-glucose Co-transporter 2 (Sglt2) Inhibitors: Gliflozinsmentioning

confidence: 99%

Biocatalyzed synthesis of antidiabetic drugs: A review

Alcántara

2017

Biocatalysis and Biotransformation

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“…Yarrowia lipolytica has been established as a heterologous host for EH overexpression in the company Oxyrane Ltd. [102]. The origin of some EHs that were used in various biotransformation reactions was released in different patents [35,118,141].…”

Section: Bromo Epoxidementioning

confidence: 99%

“…With yet another overexpressed EH in Y. lipolytica (Oxy-3) (S)-4-acetoxy-buten-1,2-oxide was obtained in 20% yield and 97.8% ee starting from the racemate [102]. The (S)-epoxide can easily be converted to (S)-3-hydroxytetrahydrofuran (Figure 8.34), a compound used for the synthesis of HIV protease inhibitors amprenavir and fosamprenavir [147].…”

Section: Protected Epoxy Alcoholsmentioning

confidence: 99%

“…More recently, EHs exhibiting opposite enantiopreference toward the two antipodes of p-NSO were also described. Two of them, Kau2 and Kau8, were isolated from biofilter-derived metagenomes (Kotik et al, 2010), and two others, oxy-4 and oxy-10, from yeast (Pienaar et al, 2008). It should be noticed that the remaining epoxides of Kau2-and Oxy-10-mediated kinetic resolutions were determined to be(R)-p-NSO, which is the correct enantiomer for the synthesis of (R)-Nifenalol.…”

Section: Nitrostyrene Oxidementioning

confidence: 99%

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Epoxide Hydrolases and their Application in Organic Synthesis

2016

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c h a p t e r 8 INTRODUCTIONOrganic chemists have become interested in enzymes as catalysts due to their high efficiencies and specificities. Moreover, recent progress in molecular biology and enzyme-related research areas enabled and simplified the production and purifica tion of recombinant enzymes in large quantities and their engineering toward tailormade biocatalysts using straightforward mutagenesis and screening techniques. This is also true for epoxide hydrolases (EHs), as evidenced by the many published research papers about the synthetic applications of naturally occurring or engi neered EHs. EHs catalyze the opening of oxirane rings, generating a vicinal diol as the final product ( Figure 8.1). From a synthetic chemistry point of view, the most valuable EHs are those with either (i) high enantioselectivities or (ii) a combination of low enantio preference with a high level of enantioconvergence. While the former generate enan tiopure epoxides with a maximum yield of 50% in a kinetic resolution process, the latter produce ideally an enantiopure diol product with a theoretical yield of 100%. Thus, EHs provide convenient access to enantiopure epoxides or diols from racemic epoxides. Furthermore, the enantiopure diols can then often be chemically trans formed back to the corresponding epoxides with no effect on the enantiomeric excess (ee). High values of enantioselectivity or enantioconvergence are a consequence of particular enzyme-substrate interactions, which can be modulated by specific reac tion conditions or through the exchange of specific amino acids of the biocatalyst. The final stereochemical outcome of an EH-catalyzed reaction depends solely on the regioselectivity coefficients, which determine the absolute configuration and the ee of the diol product when the reaction reaches 100% conversion. During the reaction, the oxirane ring of each enantiomer is often attacked at either carbon atom, resulting in a mixture of diol enantiomers (Figure 8.2). Unfortunately, several authors used the product-derived E-value, E P (calculated from c and ee P using Sih's equation; see Ref.[1]) for characterizing the stereochemistry of the diol formation of an EH-mediated hydrolysis reaction [2,3]. This is wrong and misleading for epoxide-opening reac tions since there are two possible positions of attack for each oxirane enantiomer. The ideal enantioconvergent EH leads to deracemization of a racemic mixture of an epox ide and exhibits reversed regioselectivity for either substrate enantiomer, that is,

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Synthesis of a variety of optically active hydroxylated heterocyclic compounds using epoxide hydrolase technology

Cited by 13 publications

References 25 publications

Novel Concise Synthesis of (−)‐Clausenamide

Novel Concise Synthesis of (−)‐Clausenamide

Biocatalyzed synthesis of antidiabetic drugs: A review

Epoxide Hydrolases and their Application in Organic Synthesis

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