Mass enantiomeric excess determination

At low temperatures, the nonenzymatic reaction is reduced to a larger extent than the enzymatic reaction. The mass transfer rate is reduced to a smaller extent. Mass transfer limitation is required for high enantiomeric excess and determines the conversion rate. Therefore, the volumetric productivity decreases at lower temperatures. The equilibrium constant is considerably higher at low temperatures, resulting in a higher extent of conversion or a lower HCN requirement. Both the volumetric productivity and the required enzyme concentration increase by increasing the reaction temperature and aqueous-phase volume while meeting the required conversion and enantiomeric excess [44]. The influence of the reaction medium (solvent and water activity) is much more difficult to rationalize and predict [45],... 

Sawada, M. et al., Determination of enantiomeric excess for amino acid ester salts using FAB mass spectrometry. Chem. Commun. 1569-1570 (1998)... 

Enantiomeric excess can be detected in a number of ways. Direct observation of optical activity, that is, determination of the specific rotation [a]d of a compound, is cumbersome. Biochemical detection is also possible, although methodologies are generally specific to individual compounds or compound types. Indirect measurement through a chromatographic procedure, for example, gas chromatography or gas chromatography-mass spectrometry on a chiral stationary phase, has wide applicability and is very sensitive. 

Conversions and enantiomeric excesses (ee), obtained in ethane under supercritical conditions, are shown in Table 1. Favorable conditions for achieving good ee are high hydrogen pressure (>70 bar) and low temperature [8], The latter parameter is limited by the critical temperature of the ethane/hydrogen mixture [10]. Selectivities are about the same as those obtained in the best conventional apolar solvent, toluene. Initial reaction rates of the fast reaction could not be determined accurately. The reaction times, required for complete conversion of ethyl pyruvate, were 3 - 3.5 times lower in ethane than in toluene under otherwise identical conditions, likely due to the absence of mass transfer limitations in ethane. 

The high-throughput screening of asymmetric catalysts requires efficient techniques for the determination of enantiomeric excesses. Siuzdak and Finn recently developed a method for that purpose which makes use of kinetic resolution and mass spectrometry [19]. Various chiral secondary alcohols and amines were esterified on... 

Recently, the enantiomeric excess of a-amino acid ester hydrochlorides has been determined directly by using FAB (fast atom bombardment) mass spectrometry without chromatographic separation of the enantiomers. ... 

LebriUa has developed a chiral mass spectrometry method that has potential to determine enantiomeric excess of mixtures. The method involves an ion—molecule reaction between a neutral amine and a noncovalent charged complex (formed via ESI) consisting of a selector (cyclodextrin) and the desired selectand (chiral substrate, typically an amino acid). The protonated selector—selectand complex undergoes a guest—ligand exchange reaction with the amine. The rate of this reaction is sensitive to the chirality of the bound selectand and thus can be used to the quantify enantiomeric excess of other mixtures using suitable calibration curves. 

Standard reaction conditions. Catalysed reactions were conducted at 293 K in a Baskerville stainless steel reactor of volume 150 ml. 7.2 ml pyruvate ester (65 mmol) and alkaloid (0.17 mmol cinchonidine (50 mg) or 0.17 mmol quinuclidine (19 mg) or 0.17 mmol of each) were dissolved in 12.5 ml dichloromethane and added to the catalyst (250 mg) in the reactor. The reactor was operated at 30 bar in a constant pressure mode. Product analysis was by chiral gas chromatography to determine the enantiomeric excess (ee) and by GCMS to determine the masses of higher molecular weight products. 

Grigorean, G., Ramirez, I,Ahn, S.H., Lebrilla, C.B. (2000) A mass spectrometry method for the determination of enantiomeric excess in mixtures of D,L-amino acids. Anal. Chem., 72, 4275 281. 

The major composition of the Gd catalyst prepared from Gd(0-iPr)3 and ligand (7a) in a ratio of 1 2 was determined to be Gd/ligand = 2/3 by ESI-MS (electronspray ionization mass spectrometry) analysis [84a]. The mass value and the isotope distribution pattern matched well with the calculated values. NMR studies supported the formation of lanthanide cyanide. Free ligand (7a) was disilylated when treated with TMSCN. The relationship between the enantiomeric excess of the product and the ratio of Gd/ligand (Figure 13.6) was also consistent with these observations. The postulated mechanism is shown in Scheme 13.29. One of the Gd in the Gd/ligand (7a) =2 3 complex is speculated to work as Lewis acid to activate the ketone, and the other Gd center would work as a nucleophile. The two Gd centers work cooperatively to promote the reaction smoothly. 

The separation of amino acids into particular enantiomers was the subject of mass spectrometric studies but also ESI MS was applied to determine by kinetic resolution the enantiomeric excess of optically active alcohols and amines in nanoscale by diastereoselective derivatization with optically active acids [38], This method has several distinctive features among others, easily available chiral acids can be used (the authors used A -benzoyl proline derivatives), no chromatographic separations are required, it is insensitive to certain impurities, it is fast and requires only small amount of substrate (10 nmol or less). The method can take an advantage when accuracy of enantiomeric excess measurement is sufficient within 10% limits. 

Norboma-2,5-diene (0.95 mL, 9.4 mmol) and phenylacetylene (1.0 mL, 9.1 mmol) were added under to tris(acetylacetonato)cobalt (7.1 mg, 0.02 mmol) and (- -)-bicyclo[2.2.1]hept-5-ene-2,3-diylbis(diphenyl-phosphane) (14mg, 0.03 mmol) in dry THF (1 mL). The catalytically active cobalt species was then generated by adding 1 M diethylaluminum chloride in hexane (5 mL). The reaction mixture was stirred for 4h at 35 °C. i-PrOH (5mL) was added dropwise to decompose the excess of diethylaluminum chloride. The volatile constituents were removed by vacuum distillation at rt. The product was then isolated by vacuum distillation at lOO C in a Kugelrohr apparatus [a] 56.3 (c = 1, CHClj, 20°C). The H NMR and mass spectrum of the product were identical to those of a reference sample yield 100%, enantiomeric purity 98.4% ee, both determined by GC with naphthalene as standard using a 40-m Lipodex-C column. Retention times (—)-product 120.7 min, (-l-)-product 123.7 min (column temperature 104 C, carrier gas Hj, flow rate 4-5 mL min at 1.7 bar, injection temperature 170°C). 

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