Unexpected rearrangement of enantiomerically pure 3‐aminoquinuclidine as a simple way of preparing diastereomeric octahydropyrrolo[2,3‐c]pyridine derivatives

Goljer, Igor; Molinari, Albert; He, Yanan; Nogle, Lisa; Sun, Wen‐Hua; Campbell, Brandon; McConnell, Oliver J.

doi:10.1002/chir.20663

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…However, for proprietary reasons fewer than twenty AC determinations of pharmaceutical compounds via VCD method have been recently reported. 52,[111][112][113][114][115][116][117][118][119][120][121][122] The following examples demonstrate that VCD has become a useful tool in assisting the study of structure-activity relationships (SAR) and/or structure-property relationships (SPR) for chiral pharmaceutical compounds.…”

Section: Determination Of Absolute Configuration Of Pharmaceutical Momentioning

confidence: 99%

Determination of Absolute Configuration of Chiral Molecules Using Vibrational Optical Activity: A Review

Wang²,

Dukor³

et al. 2011

Appl Spectrosc

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291

218

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Determination of the absolute handedness, known as absolute configuration (AC), of chiral molecules is an important step in any field related to chirality, especially in the pharmaceutical industry. Vibrational optical activity (VOA) has become a powerful tool for the determination of the AC of chiral molecules in the solution state after nearly forty years of evolution. VOA offers a novel alternative, or supplement, to X-ray crystallography, permitting AC determinations on neat liquid, oil, and solution samples without the need to grow single crystals of the pure chiral sample molecules as required for X-ray analysis. By comparing the sign and intensity of the measured VOA spectrum with the corresponding ab initio density functional theory (DFT) calculated VOA spectrum of a chosen configuration, one can unambiguously assign the AC of a chiral molecule. Comparing measured VOA spectra with calculated VOA spectra of all the conformers can also provide solution-state conformational populations. VOA consists of infrared vibrational circular dichroism (VCD) and vibrational Raman optical activity (ROA). Currently, VCD is used routinely by researchers in a variety of backgrounds, including molecular chirality, asymmetric synthesis, chiral catalysis, drug screening, pharmacology, and natural products. Although the application of ROA in AC determination lags behind that of VCD, with the recent implementation of ROA subroutines in commercial quantum chemistry software, ROA will in the future complement VCD for AC determination. In this review, the basic principles of the application of VCD to the determination of absolute configuration in chiral molecules are described. The steps required for VCD spectral measurement and calculation are outlined, followed by brief descriptions of recently published papers reporting the determination of AC in small organic, pharmaceutical, and natural product molecules.

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Section: Determination Of Absolute Configuration Of Pharmaceutical Momentioning

confidence: 99%

Determination of Absolute Configuration of Chiral Molecules Using Vibrational Optical Activity: A Review

Wang²,

Dukor³

et al. 2011

Appl Spectrosc

Self Cite

291

218

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“…83 Via an unexpected rearrangement reaction, Goijer et al obtained the 3,7-diasteroemers of 49 from the reaction of enantiopure 3-aminequinuclidine and 2-chloropyrimidine. 84 Again, the diastereomers could be differentiated based on NMR spectroscopic, and the AC was determined by VCD after HPLC separations of the diastereomers.…”

Section: The Journal Of Organic Chemistrymentioning

confidence: 99%

Absolute Configurations of Synthetic Molecular Scaffolds from Vibrational CD Spectroscopy

2019

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Vibrational circular dichroism (VCD) spectroscopy is one of the most powerful techniques for the determination of absolute configurations (AC), as it does not require any specific UV/vis chromophores, no chemical derivatization, and no growth of suitable crystals. In the past decade, it has become increasingly recognized by chemists from various fields of synthetic chemistry such as total synthesis and drug discovery as well as from developers of asymmetric catalysts. This perspective article gives an overview about the most important experimental aspects of a VCD-based AC determination and explains the theoretical analysis. The comparison of experimental and computational spectra that leads to the final conclusion about the AC of the target molecules is described. In addition, the review summarizes unique VCD studies carried out in the period 2008−2018 that focus on the determination of unknown ACs of new compounds, which were obtained in its enantiopure form either through direct asymmetric synthesis or chiral chromatography.

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“…Most of the reported chiroptical spectral analyses for chiral drugs were accomplished via visual spectral analyses. A table summarizing the chiral drugs whose ACs were investigated [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90] using chiroptical spectroscopic methods are summarized in Table 1. Occasional reviews have also highlighted some of these chiral drugs [42,65,91,92].…”

Section: Chiroptical Spectroscopic Toolsmentioning

confidence: 99%

Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

Polavarapu

2016

Molecules

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Chiroptical spectroscopy has emerged as a promising tool for the determination of absolute configurations and predominant conformations of chiral molecules in academic laboratories. This promise has led to the adaption of chiroptical spectroscopic methods as valuable tools in chiral drug discovery research programs of the pharmaceutical industry. Most major pharmaceutical companies have invested in in-house chiroptical spectroscopy applications and reported successful outcomes. In the context of continuously increasing applications of chiroptical spectroscopy for chiral molecular structure determination, a review of recent developments and applications for chiral drugs is presented in this manuscript.

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Unexpected rearrangement of enantiomerically pure 3‐aminoquinuclidine as a simple way of preparing diastereomeric octahydropyrrolo[2,3‐c]pyridine derivatives

Cited by 4 publications

References 32 publications

Determination of Absolute Configuration of Chiral Molecules Using Vibrational Optical Activity: A Review

Determination of Absolute Configuration of Chiral Molecules Using Vibrational Optical Activity: A Review

Absolute Configurations of Synthetic Molecular Scaffolds from Vibrational CD Spectroscopy

Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

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