<sup>1</sup>H- and <sup>13</sup>C-nmr Assignments for Taxol, 7-epi-Taxol, and Cephalomannine

Chmurny, Gwendolyn N.; Hilton, Bruce D.; Brobst, Susan W.; Look, Sally A.; Witherup, Keith M.; Beutler, John A.

doi:10.1021/np50082a002

Cited by 112 publications

(81 citation statements)

References 6 publications

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“…The purified paclitaxel was identified by high-resolution electrospray tandem mass spectrometry (HR-ESI-MS/MS), and 1H NMR (see Supplementary File). These data are in good agreement with those reported in the literature [36,37] …”

Section: Purification Of Paclitaxel On Large Scalesupporting

confidence: 93%

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Efficient purification of paclitaxel from yews using high-performance displacement chromatography technique

Watchueng

Kamnaing

Gao

et al. 2011

Journal of Chromatography A

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Efficient purification of paclitxel from yews using high-performance displacement chromatography technique Watchueng, J.; Kamnaing, P.; Gao, JM.; Kiyota, T.; Yeboah, F.; Konishi, Y.Journal of Chromatography A, 1218Chromatography A, (2011Chromatography A, ) 2929Chromatography A, -2935 Paclitaxel was purified using high-performance displacement chromatography (HPDC) technique, but not by the mechanism of HPDC. On small scale, paclitaxel was extracted with methanol from dry needles of Taxus canadensis and was enriched by extracting with chloroform after removing water-soluble hydrophilic components and hexane-soluble hydrophobic components. Then, 93-99% purity of paclitaxel was obtained using the HPDC technique. On large scale, taxanes were enriched by solvent partitioning between acetic acid/MeOH/H 2 O and hexane and extracted with CH 2 Cl 2 . Taxanes except paclitaxel were further removed by extracting with methanol-water-trifluoroacetic acid (1.0:98.9:0.1, v/v/v). Applying HPDC technique to water-insoluble substances is problematic as this method requires a highly aqueous solvent system. In order to overcome this incompatibility, a system was set up where paclitaxel, although in low concentration, was extracted by methanol-water-trifluoroacetic acid (10.0:89.9:0.1, v/v/v). Recycling the extracting solvent to ensure minimal volume, the extracted paclitaxel was adsorbed on a C 18 trap column. A C 18 column of 4.6 mm internal diameter was then connected to the trap column. The HPDC technique was thus carried out using an isocratic acetonitrile-water-trifluoroacetic acid (30.0:69.9:0.1, v/v/v) mobile phase consisting of a displacer cetylpyridinium trifluoroacetate (3 mg/mL). Paclitaxel was co-eluted with the displacer and spontaneously crystallized. The crystal (114 mg) showed 99.4% purity and only 10% of paclitaxel in the starting crude extract was lost during the enrichment/purification processes. This large scale purification method was successfully applied to purify paclitaxel from Chinese yew in small scale, suggesting general applicability of the method. This is the first report of purifying a water-insoluble natural product using HPDC technique.Crown

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Section: Purification Of Paclitaxel On Large Scalesupporting

confidence: 93%

“…The structure of the purified paclitaxel was identified by HR-ESI-MS/MS, and 1 H NMR (see Supplementary File). These data are in good agreement with those reported in the literature [36,37], and confirm that the purified compound is paclitaxel.…”

Section: Purification Of Paclitaxel From Chinese Yew On Small Scalesupporting

confidence: 92%

Efficient purification of paclitaxel from yews using high-performance displacement chromatography technique

Watchueng

Kamnaing

Gao

et al. 2011

Journal of Chromatography A

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“…An alternative implementation of GARP-1 decoupling using a scan-dependant decoupler offset of a limited 13C spectral region has recently been reported. The NMR data of taxol shown here generally refer to assignments that are well documented, 16,[24][25][26][27] and the observed spectra ( Figure 2) were found to be qualitatively identical with the published data. …”

supporting

confidence: 84%

A Routine Experimental Protocol for qHNMR Illustrated with Taxol

2007

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Quantitative 1 H NMR (qHNMR) provides a value-added dimension to the standard spectroscopic data set involved in structure analysis, especially when analyzing bioactive molecules and elucidating new natural products. The qHNMR method can be integrated into any routine qualitative workflow without much additional effort by simply establishing quantitative conditions for the standard solution 1 H NMR experiments. Moreover, examination of different chemical lots of taxol and a Taxus brevifolia extract as working examples led to a blueprint for a generic approach to performing a routinely practiced 13 C-decoupled qHNMR experiment, and for recognizing its potential and main limitations. The proposed protocol is based on a newly assembled 13 C GARP broadband decoupled proton acquisition sequence that reduces spectroscopic complexity by removal of carbon satellites. The method is capable of providing qualitative and quantitative NMR data simultaneously and covers various analytes from pure compounds to complex mixtures such as metabolomes. Due to a routinely achievable dynamic range of 300:1 (0.3%) or better, qHNMR qualifies for applications ranging from reference standards to biologically active compounds to metabolome analysis. Providing a "cookbook" approach to qHNMR, acquisition conditions are described that can be adapted for contemporary NMR spectrometers of all major manufacturers. The world's pool of natural products plays an important role as an (in)exhaustible resource for evolutionary-shaped molecules. Natural products are valuable research tools, which in part is due to their biological potency (see comprehensive reviews [1][2][3][4] ). When natural products are used as biomedical agents, and in consistency with the pharmacophore model, it is the combination of their specific chemical structure and/or reactivity that forms their relationship with a biological target and ultimately defines their essential structural features. Consequently, chemical constitution plays a key role in biological activity, and, therefore, all structure related information obtainable from a biologically active agent is by default relevant. Ultimately, any variation of structural parameters has the potential to introduce variations in biological activity. This relationship holds regardless of the magnitude of the biological perturbation, i.e., whether there is slight or a substantial change in potency, or even an alteration in the type of biological response. The well-documented subtleties of mammalian hormonal steroids can serve as a distinguished example in this regard.⊥ Dedicated to Dr. Norman R. Farnsworth on the occasion of his 77 th birthday.* To whom correspondence should be addressed. Tel (312) 355-1949355- . Fax (312)-355-2693. gfp@uic.edu. Supporting Information Available.This material is available free of charge via the Internet at http://pubs.acs.org. Further information on qNMR methodology, instrument parameter files for the NMR major manufacturer's spectrometers, and original FIDs of the taxol qHNMR experime...

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“…16 The T-shaped conformers superimpose well with the binding conformation of Taxol inˇ-tubulin. 17,31 The structural information determined by solution NMR in nonpolar organic solvents 18,19 or mixture of polar and organic solvents 15 have significant differences 20,21 and we are thus motivated to investigate the molecular structure of Taxol in solid phase. In this work, we applied 13 C solid-state NMR spectroscopy to characterize the structure of Taxol in powder form.…”

Section: Methodsmentioning

confidence: 99%

“…The 13 C chemical shift assignments were determined (Table 1) on the basis of solution-state 13 C NMR assignments. 18 Referring to Table 1, most of the signals arising from the taxane ring residues exhibit well-resolved doublets, with a splitting that ranges from 50-150 Hz. Others, C-15, C-16 and C-17, revealed as singlets, while for C-2 0 and 4-Me, the corresponding spectral resolution is too poor to resolve as doublets.…”

Section: Nmr Spectroscopymentioning

confidence: 99%

Solid‐state NMR studies of the molecular structure of Taxol

Tzou

Chu

2006

Magnetic Reson in Chemistry

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¹H- and ¹³C-nmr Assignments for Taxol, 7-epi-Taxol, and Cephalomannine

Abstract: The 1H- and 13C-nmr spectra of taxol [1], 7-epi-taxol [2], and cephalomannine [3] were assigned using modern 1D and 2D nmr methods. Preliminary conformational information was obtained by nOe spectroscopy.

Cited by 112 publications

References 6 publications

Efficient purification of paclitaxel from yews using high-performance displacement chromatography technique

Efficient purification of paclitaxel from yews using high-performance displacement chromatography technique

A Routine Experimental Protocol for qHNMR Illustrated with Taxol

Solid‐state NMR studies of the molecular structure of Taxol

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1H- and 13C-nmr Assignments for Taxol, 7-epi-Taxol, and Cephalomannine

Abstract: The 1H- and 13C-nmr spectra of taxol [1], 7-epi-taxol [2], and cephalomannine [3] were assigned using modern 1D and 2D nmr methods. Preliminary conformational information was obtained by nOe spectroscopy.

Cited by 112 publications

References 6 publications

Efficient purification of paclitaxel from yews using high-performance displacement chromatography technique

Efficient purification of paclitaxel from yews using high-performance displacement chromatography technique

A Routine Experimental Protocol for qHNMR Illustrated with Taxol

Solid‐state NMR studies of the molecular structure of Taxol

Contact Info

Product

Resources

About

¹H- and ¹³C-nmr Assignments for Taxol, 7-epi-Taxol, and Cephalomannine