Structural Analysis of d -Phenylglycinamide Salts Uncovers Potential Pitfalls in Chiral Resolution via Diastereomeric Salt Formation

Natalia Tumanova, Vanessa Seiler, Nikolay Tumanov, Koen Robeyns, Yaroslav Filinchuk, Johan Wouters, Tom Leyssens

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

d-Phenyglycinamide (d-PGA) was shown to form diastereomeric salts with a series of dicarboxylic acids (malic, methylsuccinic, camphoric) and the drug naproxen. Structural analysis of the 21 newly discovered forms was performed in order to investigate the potential of d-PGA as a base agent for chiral resolution via diastereomeric salt formation. Malic and methylsuccinic dicarboxylic acids formed salts with 1:1 and 2:1 stoichiometries, whereas camphoric acid and naproxen yielded only 1:1 salts. In the d-PGA/naproxen system, variable-temperature in situ synchrotron X-ray diffraction gave access to two additional nonambient 1:1 salts. d-PGA subjected to liquid-assisted grinding with the racemic forms of the tested compounds to study chiral resolution in the solid state yielded in most of the cases complicated mixtures of diastereomeric salts or salts with the racemates (when both enantiomers and d-PGA crystallize in one structure), thereby suggesting that the use of d-PGA for chiral resolution may be challenging.
langue originaleAnglais
Pages (de - à)3652-3659
Nombre de pages8
journalCrystal Growth & Design
Volume19
Numéro de publication7
Date de mise en ligne précoce21 juin 2019
Les DOIs
étatPublié - 3 juil. 2019

Empreinte digitale

structural analysis
Structural analysis
Salts
salts
Naproxen
Dicarboxylic Acids
dicarboxylic acids
Acids
Enantiomers
enantiomers
grinding
phenylglycinamide
Synchrotrons
Stoichiometry
stoichiometry
synchrotrons
drugs
solid state
X ray diffraction
acids

Citer ceci

Tumanova, Natalia ; Seiler, Vanessa ; Tumanov, Nikolay ; Robeyns, Koen ; Filinchuk, Yaroslav ; Wouters, Johan ; Leyssens, Tom. / Structural Analysis of d -Phenylglycinamide Salts Uncovers Potential Pitfalls in Chiral Resolution via Diastereomeric Salt Formation. Dans: Crystal Growth & Design. 2019 ; Vol 19, Numéro 7. p. 3652-3659.
@article{e6c21a8cbd534e72973db39411c5d059,
title = "Structural Analysis of d -Phenylglycinamide Salts Uncovers Potential Pitfalls in Chiral Resolution via Diastereomeric Salt Formation",
abstract = "d-Phenyglycinamide (d-PGA) was shown to form diastereomeric salts with a series of dicarboxylic acids (malic, methylsuccinic, camphoric) and the drug naproxen. Structural analysis of the 21 newly discovered forms was performed in order to investigate the potential of d-PGA as a base agent for chiral resolution via diastereomeric salt formation. Malic and methylsuccinic dicarboxylic acids formed salts with 1:1 and 2:1 stoichiometries, whereas camphoric acid and naproxen yielded only 1:1 salts. In the d-PGA/naproxen system, variable-temperature in situ synchrotron X-ray diffraction gave access to two additional nonambient 1:1 salts. d-PGA subjected to liquid-assisted grinding with the racemic forms of the tested compounds to study chiral resolution in the solid state yielded in most of the cases complicated mixtures of diastereomeric salts or salts with the racemates (when both enantiomers and d-PGA crystallize in one structure), thereby suggesting that the use of d-PGA for chiral resolution may be challenging.",
author = "Natalia Tumanova and Vanessa Seiler and Nikolay Tumanov and Koen Robeyns and Yaroslav Filinchuk and Johan Wouters and Tom Leyssens",
year = "2019",
month = "7",
day = "3",
doi = "10.1021/acs.cgd.8b01769",
language = "English",
volume = "19",
pages = "3652--3659",
journal = "Crystal Growth and Design",
issn = "1528-7483",
publisher = "American Chemical Society",
number = "7",

}

Structural Analysis of d -Phenylglycinamide Salts Uncovers Potential Pitfalls in Chiral Resolution via Diastereomeric Salt Formation. / Tumanova, Natalia; Seiler, Vanessa; Tumanov, Nikolay; Robeyns, Koen; Filinchuk, Yaroslav; Wouters, Johan; Leyssens, Tom.

Dans: Crystal Growth & Design, Vol 19, Numéro 7, 03.07.2019, p. 3652-3659.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Structural Analysis of d -Phenylglycinamide Salts Uncovers Potential Pitfalls in Chiral Resolution via Diastereomeric Salt Formation

AU - Tumanova, Natalia

AU - Seiler, Vanessa

AU - Tumanov, Nikolay

AU - Robeyns, Koen

AU - Filinchuk, Yaroslav

AU - Wouters, Johan

AU - Leyssens, Tom

PY - 2019/7/3

Y1 - 2019/7/3

N2 - d-Phenyglycinamide (d-PGA) was shown to form diastereomeric salts with a series of dicarboxylic acids (malic, methylsuccinic, camphoric) and the drug naproxen. Structural analysis of the 21 newly discovered forms was performed in order to investigate the potential of d-PGA as a base agent for chiral resolution via diastereomeric salt formation. Malic and methylsuccinic dicarboxylic acids formed salts with 1:1 and 2:1 stoichiometries, whereas camphoric acid and naproxen yielded only 1:1 salts. In the d-PGA/naproxen system, variable-temperature in situ synchrotron X-ray diffraction gave access to two additional nonambient 1:1 salts. d-PGA subjected to liquid-assisted grinding with the racemic forms of the tested compounds to study chiral resolution in the solid state yielded in most of the cases complicated mixtures of diastereomeric salts or salts with the racemates (when both enantiomers and d-PGA crystallize in one structure), thereby suggesting that the use of d-PGA for chiral resolution may be challenging.

AB - d-Phenyglycinamide (d-PGA) was shown to form diastereomeric salts with a series of dicarboxylic acids (malic, methylsuccinic, camphoric) and the drug naproxen. Structural analysis of the 21 newly discovered forms was performed in order to investigate the potential of d-PGA as a base agent for chiral resolution via diastereomeric salt formation. Malic and methylsuccinic dicarboxylic acids formed salts with 1:1 and 2:1 stoichiometries, whereas camphoric acid and naproxen yielded only 1:1 salts. In the d-PGA/naproxen system, variable-temperature in situ synchrotron X-ray diffraction gave access to two additional nonambient 1:1 salts. d-PGA subjected to liquid-assisted grinding with the racemic forms of the tested compounds to study chiral resolution in the solid state yielded in most of the cases complicated mixtures of diastereomeric salts or salts with the racemates (when both enantiomers and d-PGA crystallize in one structure), thereby suggesting that the use of d-PGA for chiral resolution may be challenging.

UR - http://pubs.acs.org/doi/10.1021/acs.cgd.8b01769

UR - http://www.mendeley.com/research/structural-analysis-scpdscp-phenylglycinamide-salts-uncovers-potential-pitfalls-chiral-resolution-vi

U2 - 10.1021/acs.cgd.8b01769

DO - 10.1021/acs.cgd.8b01769

M3 - Article

VL - 19

SP - 3652

EP - 3659

JO - Crystal Growth and Design

JF - Crystal Growth and Design

SN - 1528-7483

IS - 7

ER -