Determination of the absolute configurations of synthetic daunorubicin analogues using vibrational circular dichroism spectroscopy and density functional theory

Yang, Guochun; Tran, H. D.; Fan, Eric; Shi, Wei; Lowary, Todd L.; Xu, Yunjie

doi:10.1002/chir.20825

Cited by 16 publications

(8 citation statements)

References 74 publications

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“…The majority of these molecules were investigated by the groups of Stephens 11,[124][125][126][127][128] and Joseph-Nathan, [129][130][131][132][133][134][135][136][137][138][139] but additional groups in natural-product research have begun to take advantage of VCD for AC determinations. [140][141][142][143][144][145][146][147][148][149] Nafie published an extensive review on the AC determination of natural products by VCD in 2008, 10 and as a result only a few more recent examples are described in this section.…”

Section: Determination Of Absolute Configuration Of Natural Product Mmentioning

confidence: 99%

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

Wang²,

Dukor³

et al. 2011

Appl Spectrosc

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 Natural Product Mmentioning

confidence: 99%

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

Wang²,

Dukor³

et al. 2011

Appl Spectrosc

291

218

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show abstract

“…IR spectroscopy itself can, in some cases, also be used to determine the relative stereochemistry, and the combination of VCD with IR appears promising for assigning the stereochemistry if the spectra are analyzed in detail. The number of applications of VCD for the determination of the AC of diastereoisomers increases every year, − but in most cases the relative stereochemistry is already known. In the present study, the AC of all stereoisomers of tadalafil is established from VCD.…”

Section: Introductionmentioning

confidence: 99%

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

Qiu¹,

Gussem

Tehrani³

et al. 2013

J. Med. Chem.

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The stereochemistry of all four stereoisomers of tadalafil is determined using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD) spectroscopy. By comparing experimentally obtained VCD spectra to computationally simulated ones, the absolute configuration of the enantiomeric pair (6R, 12aR)/(6S, 12aS) can be confidently assigned without prior knowledge of their relative stereochemistry. IR and NMR spectra are used to aid the assignment of the relative stereochemistry. The IR and VCD difference spectra further confirm the assignment of all stereoisomers. ECD and ORD spectra are used to investigate the complementarity of the three chiroptical techniques. VCD spectroscopy itself is found to have the ability to identify diastereoisomers, and simultaneous use of these chiroptical spectroscopic methods and NMR chemical shifts aids in increasing the reliability of stereochemistry assignment of diastereoisomers.

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“…15 Currently, most applications of circular dichroism and ORD are restricted to pairs of enantiomers. For VCD some examples have been published where the technique has been used for the determination of the AC for diastereomers [16][17][18][19][20][21][22][23][24][25][26] although this number is vastly smaller than the number of applications for enantiomers. Moreover, in many cases the relative stereochemistry of the asymmetric carbons is already known.…”

Section: Introductionmentioning

confidence: 99%

Vibrational Circular Dichroism versus Optical Rotation Dispersion and Electronic Circular Dichroism for diastereomers: the stereochemistry of 3-(1′-hydroxyethyl)-1-(3′-phenylpropanoyl)-azetidin-2-one

Gussem

Bultinck

Feledziak

et al. 2012

Phys. Chem. Chem. Phys.

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The absolute configuration of a relatively large and conformationally flexible chiral compound, 3-(1'-hydroxyethyl)-1-(3'-phenylpropanoyl)-azetidin-2-one, is determined using Vibrational Circular Dichroism (VCD) spectroscopy, Optical Rotation Dispersion (ORD) and Electronic Circular Dichroism (ECD). To that end a state of the art experimental VCD spectrum is compared to a theoretical spectrum and the absolute configuration is assigned. ORD and ECD are also used in the assignment to investigate the complementarity of the three techniques. VCD spectroscopy is found to have important advantages over ORD and ECD for diastereomers. The concept of robust modes is applied to this conformationally flexible molecule, showing that its use is limited for such large and flexible molecules.

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Determination of the absolute configurations of synthetic daunorubicin analogues using vibrational circular dichroism spectroscopy and density functional theory

Cited by 16 publications

References 74 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

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

Vibrational Circular Dichroism versus Optical Rotation Dispersion and Electronic Circular Dichroism for diastereomers: the stereochemistry of 3-(1′-hydroxyethyl)-1-(3′-phenylpropanoyl)-azetidin-2-one

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