Resolution of optical isomers of 4-amino-p-chlorobutyric acid lactam by co-crystallization

Caira, Mino R.; Nassimbeni, Luigi R.; Scott, Janet L.; Wildervanck, Alexander F.

doi:10.1007/bf01677103

Cited by 2 publications

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“…Alternatively cocrystallization may be enantiospecific, occurring only between an enantiopure coformer and one enantiomer of the target molecule. Enantiospecific cocrystallizations have been reported sporadically over the last 20 years, − including a recent example that has been developed to give chiral resolution with high enantiomeric excess . The same quandary is found for diastereomeric cocrystal pairs as for salts: how to select or design a coformer that will give a sufficiently large stability gap between the pair to strongly resolve the two enantiomers.…”

Section: Introductionmentioning

confidence: 92%

Analysis of Enantiospecific and Diastereomeric Cocrystal Systems by Crystal Structure Prediction

Habgood

2013

Crystal Growth & Design

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Cocrystals offer two novel variants on the classic salt formation method of chiral resolution. Diastereomeric cocrystal pairs are directly analogous to salts but without the requirement for proton transfer. Conversely, a coformer that cocrystallizes with one enantiomer but not the other (enantiospecific cocrystallization) has recently been shown to give high enantiomeric yield. For either variant an understanding of intermolecular interactions is vital. In this study computational crystal structure prediction (CSP) is applied to three recently reported examples: levetiracetam with mandelic acid and with tartaric acid, which display enantiospecific cocrystallization, and tartaric acid with malic acid, which forms a diastereomeric cocrystal pair. The ability of CSP techniques to predict the experimental cocrystal structures is demonstrated. The chirally selective interactions are determined using the unique capabilities of CSP, with reference to alternative structures for each cocrystal system, including the hypothetical diastereomeric twins of the levetiracetam cocrystals. In each case, chiral selectivity can be described in terms of the dominant R 2 2(8) dimer’s response to the change in enantiomer. It is concluded that when designing a coformer for chiral resolution a predilection toward a single, orientationally restrictive intermolecular motif, with minimal ability to form alternative motifs, is the best strategy.

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Section: Introductionmentioning

confidence: 92%

Analysis of Enantiospecific and Diastereomeric Cocrystal Systems by Crystal Structure Prediction

Habgood

2013

Crystal Growth & Design

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Chemistry and Insulin-Mimetic Properties of Bis(acetylacetonate)oxovanadium(IV) and Derivatives¹

et al. 2000

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The syntheses and the solid state structural and spectroscopic solution characterizations of VO(Me-acac)2 and VO(Et-acac)2 (where Me-acac is 3-methyl-2,4-pentanedionato and Et-acac is 3-ethyl-2,4-pentanedionato) have been conducted since both VO(acac)2 and VO(Et-acac)2 have long-term in vivo insulin-mimetic effects in streptozotocin-induced diabetic Wistar rats. X-ray structural characterizations of VO(Me-acac)2 and VO(Et-acac)2 show that both contain five-coordinate vanadium similar to the parent VO(acac)2. The unit cells for VO(Et-acac)2 and VO(Me-acac)2 are both triclinic, P1, with a = 9.29970(10) A, b = 13.6117(2) A, c = 13.6642(2) A, alpha = 94.1770(10) degrees, beta = 106.4770(10) degrees, gamma = 106.6350(10) degrees for VO(Et-acac)2 and a = 7.72969(4) A, b = 8.1856(5) A, c = 11.9029(6) A, alpha = 79.927(2) degrees, beta = 73.988(2)degrees, gamma = 65.1790(10)degrees for VO(Me-acac)2. The total concentration of EPR-observable vanadium(IV) species for VO(acac)2 and derivatives in water solution at 20 degreesC was determined by double integration of the EPR spectra and apportioned between individual species on the basis of computer simulations of the spectra. Three species were observed, and the concentrations were found to be time, pH, temperature, and salt dependent. The three complexes are assigned as the trans-VO(acac)2.H2O adduct, cis-VO(acac)2.H2O adduct, and a hydrolysis product containing one vanadium atom and one R-acac- group. The reaction rate for conversion of species was slower for VO(acac)2 than for VO(malto)2, VO(Et-acac)2, and VO(Me-acac)2; however, in aqueous solution the rates for all of these species are slow compared to those of other vanadium species. The concentration of vanadium(V) species was determined by 51V NMR. The visible spectra were time dependent, consistent with the changes in species concentrations that were observed in the EPR and NMR spectra. EPR and visible spectroscopic studies of solutions prepared as for administration to diabetic rats documented both a salt effect on speciation and formation of a new halogen-containing complex. Compound efficacy with respect to long-term lowering of plasma glucose levels in diabetic rats traces the concentration of the hydrolysis product in the administration solution.

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Resolution of optical isomers of 4-amino-p-chlorobutyric acid lactam by co-crystallization

Cited by 2 publications

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Analysis of Enantiospecific and Diastereomeric Cocrystal Systems by Crystal Structure Prediction

Analysis of Enantiospecific and Diastereomeric Cocrystal Systems by Crystal Structure Prediction

Chemistry and Insulin-Mimetic Properties of Bis(acetylacetonate)oxovanadium(IV) and Derivatives¹

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Resolution of optical isomers of 4-amino-p-chlorobutyric acid lactam by co-crystallization

Cited by 2 publications

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Analysis of Enantiospecific and Diastereomeric Cocrystal Systems by Crystal Structure Prediction

Analysis of Enantiospecific and Diastereomeric Cocrystal Systems by Crystal Structure Prediction

Chemistry and Insulin-Mimetic Properties of Bis(acetylacetonate)oxovanadium(IV) and Derivatives1

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Chemistry and Insulin-Mimetic Properties of Bis(acetylacetonate)oxovanadium(IV) and Derivatives¹