Self-induced nonequivalence in the association of D- and L-amino acid derivatives

Dobashi, Akira; Saito, Naoyuki G.; Motoyama, Yuuichi.; Hara, Shoji

doi:10.1021/ja00262a027

Cited by 82 publications

(35 citation statements)

References 4 publications

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“…This result provides evidence that dimerization of omeprazole enantiomers is taking place, since, in the opposite case, the optical rotation would be linearly dependent upon the enantiomer excess (r À s) as expected for chiral compounds. It has been proposed that H-bonds are responsible for the formation of diastereomeric dimers of N-acetylvaline tert-butyl ester enantiomers in CCl 4 at À 208 [24]. A similar structure can be postulated for omeprazole enantiomers (see Fig.…”

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confidence: 87%

Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Baciocchi

Juza²,

Classen³

et al. 2004

Helvetica Chimica Acta

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A new procedure to measure the equilibrium constants for the dimerization (homochiral and heterochiral) reactions of enantiomers in solution was applied to two different compounds, namely omeprazole and Pirkle×s alcohol, both in CHCl 3 . This procedure is based on the measurement of the optical rotation of the solution as a function of its composition, which exhibits a nonlinear dependence on the enantiomer enrichment. Such nonlinearity depends on the extent of dimerization, and it is a strong effect in the case of omeprazole, whose equilibrium constants are 14.0 AE 3.5 l/mol and 25.2 AE 4.0 l/mol for the formation of homochiral and of heterochiral dimers, respectively. Pirkle×s alcohol exhibits a weaker effect that allows only to estimate the order of magnitude of these constants, i.e., ca. 0.10 and 0.34 l/mol, respectively. Although, in solution, enantiomers and racemates of chiral compounds usually exhibit identical NMR spectra, small differences in the chemical shifts are sometimes observed (see [18] for an overview, as well as the ref. cit. therein). It is also known that nonracemic mixtures of enantiomers of compounds that strongly self-associate, e.g., amino alcohols, amides, and carboxylic acids, can exhibit anisochrony, thus reflecting the enantiomer composition even in the absence of shift reagents [19]. Association is often limited to the formation of dimers that may take place through the formation of H-bonds between enantiomers. This is the case for the enantiomers of the chiral [1,1'-binaphthalene]-2,2'-diol ( binaphthol) and 1-(anthracen-9-yl)-2,2,2-trifluoroethanol ( Pirkle×s alcohol). In the case of the enantiomers of binaphthol in CHCl 3 , we have recently been able, using an achiral chromatography column, to collect two fractions constituted of the pure enantiomer present in excess (reaching 100% e.e.) and of the racemic mixture, respectively [20]. In the case of Pirkle×s alcohol, the enantiomer enrichment of a nonracemic solution in hexane/CH 2 Cl 2 was also achieved through achiral chromatography on a silica stationary phase [12].

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confidence: 87%

Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Baciocchi

Juza²,

Classen³

et al. 2004

Helvetica Chimica Acta

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“…Since it is very possible that the stable molecular assembly structure in solution would be retained in the crystalline phase which is first formed by crystallization from the same solvent [46][47][48], we investigated the enantiomeric association mode in solutions of the racemates showing preferential enrichment. Although the variable temperature 1 H NMR technique proved to be inapplicable to deciding which molecular association mode is more stable in solution, homochiral or heterochiral [49][50][51][52], the combined use of solubility and supersolubility measurements under various conditions and number-averaged molecular weight measurement by vapor pressure osmometry turned out to be a potent tool for this objective [21]. Thus, it was concluded that a homochiral molecular assembly is essentially in preference to a heterochiral one in solutions of the racemic samples showing preferential enrichment, and that the homochiral supramolecular structure must be a 1D chain.…”

Section: Association Mode Of Enantiomers In Solutionmentioning

confidence: 99%

Chiral Symmetry Breaking Phenomenon Caused by a Phase Transition

2010

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Abstract:We report the mechanism and scope of "preferential enrichment", which is an unusual symmetry-breaking enantiomeric resolution phenomenon that is initiated by the solvent-assisted solid-to-solid transformation of a metastable polymorphic form into a thermodynamically stable one during crystallization from the supersaturated solution of certain kinds of racemic mixed crystals (i.e., solid solutions or pseudoracemates) composed of two enantiomers. The mechanism can well be interpreted in terms of a symmetrybreaking complexity phenomenon involving multistage processes that affect each other.

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“…The ratio of the enantiomers in the free, uncoupled substrate, a, as a function of the measurable quantities d and r is given by Eqn. 8 (see A p p e n d i~)~) .…”

Section: ' )mentioning

confidence: 99%

Horeau's Coupling of Enantiomers Revisited. The Reversible Coupling of Enantiomers to Form Diastereoisomers in Kinetically Labile Metal Complexes

Marty

Pasquier

Gampp

1987

Helvetica Chimica Acta

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Pairs of enantiomeric molecules (%, G) of a substrate of unknown, but incomplete enantiomeric purity may be coupled to each other through labile coordination to a metal center M. This results in the formation of an equilibrium mixture of diastereoisomeric complexes, uiz. meso-L, MRB ( = rn) and a pair of enantiomers LnM%% and L,MGB( = e), where L is an achiral auxiliary ligand. General expressions are presented for determining the ratio of enantiomers [%]o/ [G], from experimental parameters, which may be obtained from NMR measurements. Effects of diastereoselectivity are specifically considered. Limiting cases (nearly pure or nearly racemic substrates, very high or no diastereoselectivity, very large or no excess of free substrate) are discussed. The cases of additional diastereoisomerism owing to different coordination geometries and of the formation of complexes with more than two substrate molecules per metal center are also investigated. The results presented can not only be used far determining the enantiomeric excess but also for designing optimal strategies for the successive resolution of partly enriched samples.

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Self-induced nonequivalence in the association of D- and L-amino acid derivatives

Cited by 82 publications

References 4 publications

Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Chiral Symmetry Breaking Phenomenon Caused by a Phase Transition

Horeau's Coupling of Enantiomers Revisited. The Reversible Coupling of Enantiomers to Form Diastereoisomers in Kinetically Labile Metal Complexes

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