Enantiomerically pure β-phenylalanine analogues from α–β-phenylalanine mixtures in a single reactive extraction step

Verkuijl, Bastiaan J. V.; Szymański, Wiktor; Wu, Bian; Minnaard, Adriaan J.; Janssen, Dick B.; Vries, Johannes G. de; Feringa, Ben L.

doi:10.1039/b921661h

Cited by 28 publications

(20 citation statements)

References 18 publications

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“…To elucidate why Pd(PPh 3 ) 2 Cl 2 was the most active precatalyst complex, high‐pressure (HP) NMR spectroscopy was performed on this system under in situ conditions by using 13 C{ 1 H} and 31 P{ 1 H} NMR spectroscopy. At the beginning of the experiment, the 31 P{ 1 H} NMR spectrum (Figure , trace 1) displayed one signal at δ =24.30 ppm in agreement with the characterization of the pure compound . The addition of aniline caused no change in the spectrum (trace 2), whereas heating the mixture under Ar led to a broadening of the signal and an upfield shift to δ =23.86 ppm (trace 3).…”

Section: Resultssupporting

confidence: 72%

Selective Oxidative Carbonylation of Aniline to Diphenylurea with Ionic Liquids

et al. 2018

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A catalytic system for the selective oxidative carbonylation of aniline to diphenylurea based on Pd complexes in combination with imidazolium ionic liquids is presented. Both oxidants, Pd complexes, and ionic liquids affect the activity of the reaction, and the choice of oxidant determines the selectivity of the reaction. Together they allow the reaction to proceed under comparatively mild conditions without a loss of activity. Examination of the reaction by use of in situ NMR spectroscopy allowed us to observe an intermediate suggested only previously, which supported the proposed mechanism.

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Section: Resultssupporting

confidence: 72%

Selective Oxidative Carbonylation of Aniline to Diphenylurea with Ionic Liquids

et al. 2018

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“…In some cases, the use of biocatalysts is an attractive alternative option (Wohlgemuth 2010). Recently, the ammonia lyases and aminomutases (which exhibit ammonia lyase activity) have gained a lot of interest for the asymmetric synthesis of chiral α- and β-amino acids, with the advantage that they use readily available unsaturated acids as substrates (Turner 2010; Verkuijl et al 2010; Szymanski et al 2009; Wu et al 2009, 2010; Weiner et al 2008). However, most known ammonia lyases show low stability and therefore they are not compatible with the harsh reaction conditions that are usually required for industrial processes, such as high temperature, high pH, and high ammonia concentrations needed to catalyze the reverse reactions (Turner 2010).…”

Section: Introductionmentioning

confidence: 99%

Characterization of a thermostable methylaspartate ammonia lyase from Carboxydothermus hydrogenoformans

Raj

Veetil

Szymański

et al. 2011

Appl Microbiol Biotechnol

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Methylaspartate ammonia lyase (MAL; EC 4.3.1.2) catalyzes the reversible addition of ammonia to mesaconate to give (2S,3S)-3-methylaspartate and (2S,3R)-3-methylaspartate as products. MAL is of considerable biocatalytic interest because of its potential use for the asymmetric synthesis of substituted aspartic acids, which are important building blocks for synthetic enzymes, peptides, chemicals, and pharmaceuticals. Here, we have cloned the gene encoding MAL from the thermophilic bacterium Carboxydothermus hydrogenoformans Z-2901. The enzyme (named Ch-MAL) was overproduced in Escherichia coli and purified to homogeneity by immobilized metal affinity chromatography. Ch-MAL is a dimer in solution, consisting of two identical subunits (∼49 kDa each), and requires Mg2+ and K+ ions for maximum activity. The optimum pH and temperature for the deamination of (2S,3S)-3-methylaspartic acid are 9.0 and 70°C (kcat = 78 s−1 and Km = 16 mM). Heat inactivation assays showed that Ch-MAL is stable at 50°C for >4 h, which is the highest thermal stability observed among known MALs. Ch-MAL accepts fumarate, mesaconate, ethylfumarate, and propylfumarate as substrates in the ammonia addition reaction. The enzyme also processes methylamine, ethylamine, hydrazine, hydroxylamine, and methoxylamine as nucleophiles that can replace ammonia in the addition to mesaconate, resulting in the corresponding N-substituted methylaspartic acids with excellent diastereomeric excess (>98% de). This newly identified thermostable MAL appears to be a potentially attractive biocatalyst for the stereoselective synthesis of aspartic acid derivatives on large (industrial) scale.Electronic supplementary materialThe online version of this article (doi:10.1007/s00253-011-3615-6) contains supplementary material, which is available to authorized users.

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“…Non‐chromatographic separation methods aimed at partially removing key impurities recently attracted attentions. For example, some research groups successfully applied reactive extraction systems for the recovery of enantiomerically pure β‐phenylalanine analogs from α–β‐phenylalanine mixtures (Verkuijl et al, 2010), cycloolefins from cyclohexane (Gorri et al, 2010), lactic acid (Pai et al, 2002), and Penicillin G (Likidis and Schügerl, 1987; Pai et al, 2002; Yang and Cussler, 2000). In the aqueous extract of danshen (roots of Salvia multiorrihza Bunge), rosmarinic acid is one of the main impurities and is almost impossible to be eliminated completely from salvianolic acid B by conventional methods.…”

Section: Introductionmentioning

confidence: 99%

Enhanced recovery of antitumor ganoderic acid T from Ganoderma lucidum mycelia by novel chemical conversion strategy

Wang

Zhong

2011

Biotech & Bioengineering

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The removal of analog impurities with a very small sample size presents a major challenge in the purification of high-valued biochemicals such as those derived from fermentation or herbs. Ganoderic acid T (GA-T), an antitumor drug candidate, is very difficult to purify from the mycelia of medicinal mushroom Ganoderma lucidum due to co-purifying analog impurities. A novel pretreatment process with three consecutive chemical conversion steps, namely hydrolysis-acetylation-hydrolysis, was developed to convert two key analog impurities (7-O-ethyl GA-O and GA-Mk) to GA-T. It increased the GA-T amount in the 100 g dried mycelia from the initial 0.444 g to 1.621 g after the pretreatment, representing an apparent yield of 365% for the pretreatment. If the yield basis were the initial GA-T amount plus the GA-T amount from 100% conversion of 7-O-ethyl GA-O and GA-Mk in the crude extract, the yield, termed adjusted yield for the pretreatment in this work, would still reach 90.8%. Furthermore, the subsequent RP-HPLC purification was considerably enhanced due to the conversion of the analog impurities. This game-changer strategy achieved a daily GA-T throughput of 2.9 g with 95% purity (mass based). Even at the laboratory scale, it is now possible to produce a sufficient amount of GA-T for small-scale pharmacological and clinical evaluations. The approach of converting analog impurities that are otherwise difficult to remove to the product in a bioseparation process may be useful to achieve enhanced recovery of other medicinally useful natural products.

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Enantiomerically pure β-phenylalanine analogues from α–β-phenylalanine mixtures in a single reactive extraction step

Abstract: An efficient and selective method for the extraction of alpha-amino acids in preference over their beta-isomers using PdCl(2)(PPh(3))(2) was discovered, which enables the separation of product mixtures obtained in the enantioselective enzymatic formation of beta-amino acids.

Cited by 28 publications

References 18 publications

Selective Oxidative Carbonylation of Aniline to Diphenylurea with Ionic Liquids

Selective Oxidative Carbonylation of Aniline to Diphenylurea with Ionic Liquids

Characterization of a thermostable methylaspartate ammonia lyase from Carboxydothermus hydrogenoformans

Enhanced recovery of antitumor ganoderic acid T from Ganoderma lucidum mycelia by novel chemical conversion strategy

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