Stereochemistry of the Tadalafil Diastereoisomers: A Critical Assessment of Vibrational Circular Dichroism, Electronic Circular Dichroism, and Optical Rotatory Dispersion

Qiu, Shi; Gussem, Ewoud De; Tehrani, Kourosch Abbaspour; Sergeyev, Sergey; Bultinck, Patrick; Herrebout, Wouter A.

doi:10.1021/jm401407w

Cited by 56 publications

(44 citation statements)

References 68 publications

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“…In the field of configurational analysis it is very important to use structural information since only then a reliable assignment of the absolute configuration of new molecules is possible [1,2]. Despite enormous progress in instrumentation and methods [3] structural analysis is still a challenge, illustrated by the review of Nicolaou and Snyder [4] who presented data based on which roughly 1000 articles published between 1990 and 2004 have to be revised because of structural reasons.…”

Section: Introductionmentioning

confidence: 99%

Stereochemical analysis of (+)-limonene using theoretical and experimental NMR and chiroptical data

Reinscheid

2016

Journal of Molecular Structure

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a b s t r a c tUsing limonene as test molecule, the success and the limitations of three chiroptical methods (optical rotatory dispersion (ORD), electronic and vibrational circular dichroism, ECD and VCD) could be demonstrated. At quite low levels of theory (mpw1pw91/cc-pvdz, IEFPCM (integral equation formalism polarizable continuum model)) the experimental ORD values differ by less than 10 units from the calculated values. The modelling in the condensed phase still represents a challenge so that experimental NMR data were used to test for aggregation and solventesolute interactions. After establishing a reasonable structural model, only the ECD spectra prediction showed a decisive dependence on the basis set: only augmented (in the case of Dunning's basis sets) or diffuse (in the case of Pople's basis sets) basis sets predicted the position and shape of the ECD bands correctly. Based on these result we propose a procedure to assign the absolute configuration (AC) of an unknown compound using the comparison between experimental and calculated chiroptical data.

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Section: Introductionmentioning

confidence: 99%

Stereochemical analysis of (+)-limonene using theoretical and experimental NMR and chiroptical data

Reinscheid

2016

Journal of Molecular Structure

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“…[7] It is mostly used to assign absolute configurations of natural products, [8] pharmaceuticals, [9] and other chiral molecules including products of catalytic asymmetric reactions. [10] However,V CD spectroscopy is not only sensitive to the chirality of am olecule but also to conformational changes, [11] self-aggregation, [12] and intermolecular interactions with solvents.…”

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confidence: 99%

Stereochemical Communication within a Chiral Ion Pair Catalyst

et al. 2015

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Ionic interactions are increasingly appreciated as a key, asymmetry-inducing factor in enantioselective catalytic transformations, including those involving Brønsted acid or base catalysis, phase-transfer catalysis, and related processes. However, a detailed understanding of these interactions is often lacking. Herein, we show how an enantiopure anion enforces a chiral conformation onto a catalytically relevant achiral cation. Specifically, we use vibrational circular dichroism (VCD) spectroscopy to monitor the transmission of stereochemical information from a chiral phosphate anion to a flexible manganese(III)-salen cation. We show that VCD can be used to study solvent effects and that the obtained chiroptical data directly and quantitatively correlate with the experimentally observed enantioselectivity in an asymmetric olefin epoxidation reaction.

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“…In the near IR region, the experimental ECD (electronic circular dichroism) spectra of endoborneol enantiomers more successfully matched with calculations if equal populations of the three OH rotamers are assumed, in contrast to the energy calculation which indicates one predominant (51.5%) conformer [22]. In a recent study, Qiu et al [23] investigated the tadalafil isomers by chiroptical and NMR methods. The authors showed that the population mixes differ if different levels of theory are used for energy calculations.…”

Section: Structural Analysis Of the Menthol-type Isomersmentioning

confidence: 88%

Stereochemical analysis of menthol and menthylamine isomers using calculated and experimental optical rotation data

Reinscheid

2016

Journal of Molecular Structure

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a b s t r a c tThe complete series of menthol isomers and their corresponding amino derivatives (base and protonated/HCl forms), were investigated using experimental and theoretical data. Our study focused on the conformational and configurational analysis, and revealed that experimental data should be used in combination with calculated data. Furthermore, even in the case of the highly studied member, menthol, discrepancies were found among previously published literature values. We show that the correct determination of the population mix is a must for the correct prediction of the absolute configuration (AC) of neoisomenthol. The neoiso forms are of special interest since a number of structural inconsistences can be found in the literature. We present a stringent proof of the AC of neoisomenthol based on literature information. To the best of our knowledge, the AC of neoisomenthylamine is for the first time shown using experimental and calculated optical rotation data. A correction of a series of publications containing an important error in the assignment of (þ)-menthylamine (correct: (þ)-neomenthylamine) is presented. With 26 data pairs (experimental versus calculated) of optical rotation values a regression is performed. The AC of all 12 compounds, even the most difficult neoiso forms, could be predicted correctly using experimental low-temperature NMR data. Furthermore, if only experimental data with an optical rotation outside the range of À10 < [a] > þ10 are used, all 12 compounds would have been correctly assigned without lowtemperature NMR data as restraints.

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Stereochemistry of the Tadalafil Diastereoisomers: A Critical Assessment of Vibrational Circular Dichroism, Electronic Circular Dichroism, and Optical Rotatory Dispersion

Cited by 56 publications

References 68 publications

Stereochemical analysis of (+)-limonene using theoretical and experimental NMR and chiroptical data

Stereochemical analysis of (+)-limonene using theoretical and experimental NMR and chiroptical data

Stereochemical Communication within a Chiral Ion Pair Catalyst

Stereochemical analysis of menthol and menthylamine isomers using calculated and experimental optical rotation data

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