Dunkel, R
1992
The Revised Structure of Bistramide A (Bistratene A): Application of a New Program for the Automated Analysis of 2D INADEQUATE Spectra
Foster, M.P.; Mayne, C.L.; Dunkel, R.; Pugmire, R.J.; Grant, D.M.; Kornprobst, J.-M.; Verbist, J.-F.; Biard, J.-F. and Ireland, C.M.
Journal of the American Chemistry Society, 114(3):1110-1111, 1992. Funded by National Institutes of Health and US Department of Energy.
The two-dimensional structure of bistramide A (a.k.a. bistratene A) has been revised. The bis-amide polyether was isolated from a Lissoclinum sp. ascidian collected in the Fiji islands. The structure was established by a combination of modern NMR methods including 2D INADEQUATE, PS-DQF-COSY, HMQC and HMBC experiments. Critical to establishing the carbon-carbon backbone was CCBond, a new program for automated analysis of 2D INADEQUATE spectra. Bistramide A demonstrated in vitro cytotoxicity towards human colon tumor HCT-116 and murine leukemia L1210 cell lines with an IC50 of 0.1 µg/mL.
Improvements in the Computerized Analysis of 2D INADEQUATE Spectra
Dunkel, R.; Mayne, C.L.; Pugmire, R.J. and Grant, D.M.
Analytical Chemistry, 64 (24):3133-3149, 1992. Funded by US Department of Energy, Pittsburgh Energy Technology Center and ACERC.
The carbon skeleton of a molecule can be determined by using the powerful 2D INADEQUATE experiment, but the method suffers from very poor sensitivity at natural carbon-13 abundance. A computer program, described previously, has been significantly improved in its ability to recognize AB spectral patterns corresponding to carbon-carbon bonds which makes it possible to evaluate reliably spectra with rms S/N ratio as low as 2.5, i.e., nearly 1 order of magnitude below the level required for routine manual interpretation. Application of the INADEQUATE experiment to samples containing as little as 20 µmol of a compound of interest is now possible. The method is described in detail and critically evaluated by means of examples and simulations.
Applications of the Improved Computerized Analysis of 2D INADEQUATE Spectra
Dunkel, R.; Mayne, C.L.; Foster, M.P.; Ireland, C.M.; Li, D.; Owen, N.L.; Pugmire, R.J. and Grant, D.M.
Analytical Chemistry, 64:3150-3160, 1992. Funded by US Department of Energy, Pittsburgh Energy Technology Center and ACERC.
This paper illustrates the use of the program CCBond to determine the carbon skeletons of bioorganic molecules in low concentration samples. Discussed is the structure elucidation of bistramide A, a compound extracted from a Fijian Lissocllnum sp. and cholesterol in 71- and 20-µmol samples, respectively. The detection limit of the automated bond extraction is shown to be improved compared to the manual interpretation of 2D INADEQUATE spectra.
1991
The Revised Structure of Bistramide A (Bistratene A): Application of a New Program for the Automated Analysis of 2D INADEQUATE Spectra
Foster, M.P.; Mayne, C.L.; Dunkel, R.; Pugmire, R.J.; Grant, D.M.; Kornprobst, J.-M.; Verbist, J.-F.; Biard, J.-F. and Ireland, C.M.
Journal of the American Chemistry Society, 1991 (in press). Funded by National Institutes of Health and US Department of Energy.
The two-dimensional structure of bistramide A (a.k.a. bistratene A) has been revised. The bis-amide polyether was isolated from a Lissoclinum sp. ascidian collected in the Fiji islands. The structure was established by a combination of modern NMR methods including 2D INADEQUATE, PS-DQF-COSY, HMQC and HMBC experiments. Critical to establishing the carbon-carbon backbone was CCBond, a new program for automated analysis of 2D INADEQUATE spectra. Bistramide A demonstrated in vitro cytotoxicity towards human colon tumor HCT-116 and murine leukemia L1210 cell lines with an IC50 of 0.1 µg/mL.
1990
Computerized Analysis of 2D INADEQUATE Spectra
Dunkel, R.; Mayne, C.L.; Curtis, J.; Pugmire, R.J. and Grant, D.M.
Journal of Magnetic Resonance, 90, 290-302, 1990. Funded by ACERC and US Department of Energy.
The extraction of carbon-carbon bond information from two-dimensional INADEQUATE spectra is both time consuming and complex due to the low sensitivity of the method, the incomplete suppression of single-quantum signals, and the large size of the data sets. A computerized analysis technique is introduced which detects bonds through a nonlinear regression analysis of carefully chosen subsets of the spectral data. A quantitative one-dimensional carbon spectrum is used to establish initial values for the regression and to determine the data subsets to be used. Using statistical analysis techniques, bonds are detected with reliability and sensitivity comparable to those of careful manual interpretation.
1989
Computerized Analysis of 2D-Inadequate Spectra
Dunkel, R.; Mayne, C.L.; Pugmire, R.J. and Grant, D.M.
30th Experimental NMR Conference, Pacific Grove, California, 1989. Funded by ACERC (National Science Foundation and Associates and Affiliates).
A phase sensitive two-dimensional INADEQUATE spectrum contains carbon-carbon connectivity information; and, hence, allows one to trace molecular carbon skeletons. When a bond is present between two carbons, there are antiphase doublets centered at the chemical shift of each of the carbons. This AB pattern is displaced in F1 by the double quantum frequency that is the sum of the chemical shifts. For each pair of lines in the 1D spectrum two small regions may be defined which must contain the pattern if a bond is present. Using eight parameters the AB pattern can be modeled as a sum of four two dimensional Lorentzians. A nonlinear least squares fit of this pattern to the experimental data from the two small regions is then performed for each pair of resonances in the 1D spectrum. The best-fit values of the parameters and the covariance matrix are used to decide whether the two carbons are bonded.
The Use of Pattern Recognition With High Resolution H-1 and C-13 NMR Techniques in the Study of Fuels and Coal-Derived Liquids
Pugmire, R.J.; Dunkel, R.; Mayne, C.L. and Grant, D.M.
1989 International Conference on Coal Science, Vol. 2,Tokyo,1989. Funded by ACERC (National Science Foundation and Associates and Affiliates).
NMR spectroscopy is a widely used analytical tool for probing molecular structure and dynamics. The growth in the use of this tool for studying coal-derived liquids has been quite dramatic. Spectral analysis of these complex hydrocarbon mixtures, however, has been hampered by the vast amount of data present in any given spectrum. We have embarked on a program to use multiple-pulse, two-dimensional (2D) NMR spectroscopy (1, 2) coupled with computer assisted analysis techniques to extract structural information from these materials. Described herein is a program called CCBOND for the computer aided analysis of 2D-INADEQUATE spectra.(3)
Dunkel, R
1992
The Revised Structure of Bistramide A (Bistratene A): Application of a New Program for the Automated Analysis of 2D INADEQUATE Spectra
Foster, M.P.; Mayne, C.L.; Dunkel, R.; Pugmire, R.J.; Grant, D.M.; Kornprobst, J.-M.; Verbist, J.-F.; Biard, J.-F. and Ireland, C.M.
Journal of the American Chemistry Society, 114(3):1110-1111, 1992. Funded by National Institutes of Health and US Department of Energy.
The two-dimensional structure of bistramide A (a.k.a. bistratene A) has been revised. The bis-amide polyether was isolated from a Lissoclinum sp. ascidian collected in the Fiji islands. The structure was established by a combination of modern NMR methods including 2D INADEQUATE, PS-DQF-COSY, HMQC and HMBC experiments. Critical to establishing the carbon-carbon backbone was CCBond, a new program for automated analysis of 2D INADEQUATE spectra. Bistramide A demonstrated in vitro cytotoxicity towards human colon tumor HCT-116 and murine leukemia L1210 cell lines with an IC50 of 0.1 µg/mL.
Improvements in the Computerized Analysis of 2D INADEQUATE Spectra
Dunkel, R.; Mayne, C.L.; Pugmire, R.J. and Grant, D.M.
Analytical Chemistry, 64 (24):3133-3149, 1992. Funded by US Department of Energy, Pittsburgh Energy Technology Center and ACERC.
The carbon skeleton of a molecule can be determined by using the powerful 2D INADEQUATE experiment, but the method suffers from very poor sensitivity at natural carbon-13 abundance. A computer program, described previously, has been significantly improved in its ability to recognize AB spectral patterns corresponding to carbon-carbon bonds which makes it possible to evaluate reliably spectra with rms S/N ratio as low as 2.5, i.e., nearly 1 order of magnitude below the level required for routine manual interpretation. Application of the INADEQUATE experiment to samples containing as little as 20 µmol of a compound of interest is now possible. The method is described in detail and critically evaluated by means of examples and simulations.
Applications of the Improved Computerized Analysis of 2D INADEQUATE Spectra
Dunkel, R.; Mayne, C.L.; Foster, M.P.; Ireland, C.M.; Li, D.; Owen, N.L.; Pugmire, R.J. and Grant, D.M.
Analytical Chemistry, 64:3150-3160, 1992. Funded by US Department of Energy, Pittsburgh Energy Technology Center and ACERC.
This paper illustrates the use of the program CCBond to determine the carbon skeletons of bioorganic molecules in low concentration samples. Discussed is the structure elucidation of bistramide A, a compound extracted from a Fijian Lissocllnum sp. and cholesterol in 71- and 20-µmol samples, respectively. The detection limit of the automated bond extraction is shown to be improved compared to the manual interpretation of 2D INADEQUATE spectra.
1991
The Revised Structure of Bistramide A (Bistratene A): Application of a New Program for the Automated Analysis of 2D INADEQUATE Spectra
Foster, M.P.; Mayne, C.L.; Dunkel, R.; Pugmire, R.J.; Grant, D.M.; Kornprobst, J.-M.; Verbist, J.-F.; Biard, J.-F. and Ireland, C.M.
Journal of the American Chemistry Society, 1991 (in press). Funded by National Institutes of Health and US Department of Energy.
The two-dimensional structure of bistramide A (a.k.a. bistratene A) has been revised. The bis-amide polyether was isolated from a Lissoclinum sp. ascidian collected in the Fiji islands. The structure was established by a combination of modern NMR methods including 2D INADEQUATE, PS-DQF-COSY, HMQC and HMBC experiments. Critical to establishing the carbon-carbon backbone was CCBond, a new program for automated analysis of 2D INADEQUATE spectra. Bistramide A demonstrated in vitro cytotoxicity towards human colon tumor HCT-116 and murine leukemia L1210 cell lines with an IC50 of 0.1 µg/mL.
1990
Computerized Analysis of 2D INADEQUATE Spectra
Dunkel, R.; Mayne, C.L.; Curtis, J.; Pugmire, R.J. and Grant, D.M.
Journal of Magnetic Resonance, 90, 290-302, 1990. Funded by ACERC and US Department of Energy.
The extraction of carbon-carbon bond information from two-dimensional INADEQUATE spectra is both time consuming and complex due to the low sensitivity of the method, the incomplete suppression of single-quantum signals, and the large size of the data sets. A computerized analysis technique is introduced which detects bonds through a nonlinear regression analysis of carefully chosen subsets of the spectral data. A quantitative one-dimensional carbon spectrum is used to establish initial values for the regression and to determine the data subsets to be used. Using statistical analysis techniques, bonds are detected with reliability and sensitivity comparable to those of careful manual interpretation.
1989
Computerized Analysis of 2D-Inadequate Spectra
Dunkel, R.; Mayne, C.L.; Pugmire, R.J. and Grant, D.M.
30th Experimental NMR Conference, Pacific Grove, California, 1989. Funded by ACERC (National Science Foundation and Associates and Affiliates).
A phase sensitive two-dimensional INADEQUATE spectrum contains carbon-carbon connectivity information; and, hence, allows one to trace molecular carbon skeletons. When a bond is present between two carbons, there are antiphase doublets centered at the chemical shift of each of the carbons. This AB pattern is displaced in F1 by the double quantum frequency that is the sum of the chemical shifts. For each pair of lines in the 1D spectrum two small regions may be defined which must contain the pattern if a bond is present. Using eight parameters the AB pattern can be modeled as a sum of four two dimensional Lorentzians. A nonlinear least squares fit of this pattern to the experimental data from the two small regions is then performed for each pair of resonances in the 1D spectrum. The best-fit values of the parameters and the covariance matrix are used to decide whether the two carbons are bonded.
The Use of Pattern Recognition With High Resolution H-1 and C-13 NMR Techniques in the Study of Fuels and Coal-Derived Liquids
Pugmire, R.J.; Dunkel, R.; Mayne, C.L. and Grant, D.M.
1989 International Conference on Coal Science, Vol. 2,Tokyo,1989. Funded by ACERC (National Science Foundation and Associates and Affiliates).
NMR spectroscopy is a widely used analytical tool for probing molecular structure and dynamics. The growth in the use of this tool for studying coal-derived liquids has been quite dramatic. Spectral analysis of these complex hydrocarbon mixtures, however, has been hampered by the vast amount of data present in any given spectrum. We have embarked on a program to use multiple-pulse, two-dimensional (2D) NMR spectroscopy (1, 2) coupled with computer assisted analysis techniques to extract structural information from these materials. Described herein is a program called CCBOND for the computer aided analysis of 2D-INADEQUATE spectra.(3)