Stereochemical determination and bioactivity assessment of (S)-(+)-curcuphenol dimers isolated from the marine sponge Didiscus aceratus and synthesized through laccase biocatalysis

Cichewicz, Robert H.; Clifford, Laura J.; Lassen, Peter Rygaard; Cao, Xiaolin; Freedman, Teresa B.; Nafie, Laurence A.; Deschamps, Joshua D.; Kenyon, Victor; Flanary, Jocelyn R.; Holman, Theodore R.; Crews, Phillip

doi:10.1016/j.bmc.2005.06.020

Cited by 69 publications

(52 citation statements)

References 59 publications

(92 reference statements)

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“…[37][38][39] More recently, the spectroscopic approach of comparing observed and calculated vibrational circular dichroism (VCD) spectra, electronic circular dichroism (ECD), or optical rotation (OR) values has gained popularity due to the ease of data acquisition and the ability to calculate spectra and values with commercially available software and supercomputers or modern, powerful PCs and Linux clusters. [40][41][42][43][44][45][46][47][48][49] In the case of VCD, besides absolute stereochemistry of molecules containing one or more asymmetric centers, or planes or axes of asymmetry, i.e., atropisomerism, [50][51][52][53] additional information can be obtained, including solution conformation 54,55 and real-time reaction monitoring. 56,57 VCD has been applied specifically to pharmaceuticallyrelevant molecules.…”

Section: Introductionmentioning

confidence: 99%

Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols

McConnell¹,

He²,

Nogle³

et al. 2007

Chirality

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Phenylglycidols substituted in the 2-, 3-, and 4- positions with fluorine, chlorine, and trifluoromethyl, and with methoxy in the 3- position, were synthesized from the corresponding E-cinnamic acids and separated into their (R,R)- and (S,S)- enantiomers using subcritical fluid chromatography with mixtures of MeOH in CO(2), on either a Chiralpak AD or AS chiral stationary phase. These compounds and commercially-available (R,R)- and (S,S)-phenylglycidol were analyzed for their vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotation (OR) properties to exemplify a strategy whereby the absolute stereochemistry of common and key chiral intermediates is established early in the structure-activity and structure-property relationship phase of a drug discovery program in a pharmaceutical company. From this study, substituents in the phenyl group of the synthesized molecules were found not to grossly alter spectroscopic features, and therefore, diagnostic absorption bands in the respective VCD spectra, and the sign and shape of the measured ECD curves could be used to determine and track the absolute stereochemistry of analogs without necessarily requiring time-consuming ab initio calculations of all low energy conformers for all compounds. VCD, OR, and ECD calculations for the determination of absolute configuration carried out at the DFT level with the hybrid B3PW91 functional and the TZVP basis set were found to be especially useful in this study.

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Section: Introductionmentioning

confidence: 99%

Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols

McConnell¹,

He²,

Nogle³

et al. 2007

Chirality

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“…For flexible large molecules, such as natural products, the absolute configurations have been often determined by the model fragments of the entire molecules. 25,26 Therefore, we have addressed the conformational search using DFT calculations for the fragments of entire molecules in combination with the conformational code.…”

Section: Introductionmentioning

confidence: 99%

Structural determination of molecular stereochemistry using VCD spectroscopy and a conformational code: Absolute configuration and solution conformation of a chiral liquid pesticide, (R)‐(+)‐malathion

et al. 2009

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The absolute configuration and solution conformation of (R)-(1)-malathion were determined by using vibrational circular dichroism spectroscopy and a fragment-conformational search with a recently published conformational code. The determination of molecular stereochemistry was carried out without a conformational search using molecular mechanics calculations. Density functional theory calculations of the fragments of (R)-malathion, ethyl propionate, (R)-ethyl 2-(methylthio)propanoate, (R)-diethyl 2-(methylthio)succinate, and O,O,S-trimethyl phosphorodithioate were carried out, and the principal conformational features of the fragments were profiled. This fragment-conformational search reduces the time needed for the selection of the predominant conformations for (R)-malathion and significantly improves the accuracy of the determination of absolute configuration.

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“…When the VCD spectrum of the target compound expresses bands similar in sign, wave number, and intensity (with the calculated VCD spectrum), the absolute configuration chosen for the calculation is deduced as the same as that for the measured molecule. Besides determining absolute stereochemistry of molecules containing one or more asymmetric centers, or planes or axes of asymmetry, i.e., atropisomerism, [319][320][321][322][323][324] additional information about solution conformation can be obtained. 304,[325][326][327] Also, VCD can be used for real-time reaction monitoring.…”

Section: Current Toolbox-optical Spectroscopy Approachesmentioning

confidence: 99%

“…304,[325][326][327] Also, VCD can be used for real-time reaction monitoring. [328][329][330] VCD has been used to determine the absolute stereochemistry of natural products, 320,331 compounds derived via asymmetric enzymatic catalysis, 332 as well as carboxylic acids 333,334 and alcohols 204 in derivatized form in order to improve calculations by obviating the presence of dimers or rigidifying the molecule of interest, respectively. There are numerous published examples of VCD being applied specifically to pharmaceutically-relevant molecules, 325,335,336 as well as numerous reports where various permutations of calculated versus measured VCD, ECD and/or OR have been used to determine absolute configuration.…”

Section: Current Toolbox-optical Spectroscopy Approachesmentioning

confidence: 99%

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery—Building chiral technology toolboxes

McConnell¹,

Bach

Balibar³

et al. 2007

Chirality

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The application of Chiral Technology, or the (extensive) use of techniques or tools for the determination of absolute stereochemistry and the enantiomeric or chiral separation of racemic small molecule potential lead compounds, has been critical to successfully discovering and developing chiral drugs in the pharmaceutical industry. This has been due to the rapid increase over the past 10-15 years in potential drug candidates containing one or more asymmetric centers. Based on the experiences of one pharmaceutical company, a summary of the establishment of a Chiral Technology toolbox, including the implementation of known tools as well as the design, development, and implementation of new Chiral Technology tools, is provided.

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Stereochemical determination and bioactivity assessment of (S)-(+)-curcuphenol dimers isolated from the marine sponge Didiscus aceratus and synthesized through laccase biocatalysis

Cited by 69 publications

References 59 publications

Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols

Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols

Structural determination of molecular stereochemistry using VCD spectroscopy and a conformational code: Absolute configuration and solution conformation of a chiral liquid pesticide, (R)‐(+)‐malathion

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery—Building chiral technology toolboxes

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