Bruce D Hilton

Merck, Whitehouse Station, NJ, United States

Are you Bruce D Hilton?

Claim your profile

Publications (32)34.84 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Posaconazole, a clinically useful antifungal agent, has several known oxidative degradation products involving the piperazine ring near the center of the molecule. A novel degradant was recently isolated and characterized spectroscopically as a novel ring-contraction product incorporating a dihydroimidazolium moiety in lieu of the normally present piperazine ring.
    Magnetic Resonance in Chemistry 06/2012; 50(8):576-9. · 1.53 Impact Factor
  • Bruce D. Hilton, Gary E. Martin
    Journal of Heterocyclic Chemistry 01/2012; 49(3). · 1.22 Impact Factor
  • Journal of Heterocyclic Chemistry 01/2012; 49(5). · 1.22 Impact Factor
  • Source
    Gary E Martin, Bruce D Hilton, Kirill A Blinov
    [Show abstract] [Hide abstract]
    ABSTRACT: 1H-13C GHSQC and GHMBC spectra are irrefutably among the most valuable 2D NMR experiments for the establishment of unknown chemical structures. However, the indeterminate nature of the length of the long-range coupling(s) observed via the (n)J(CH)-optimized delay of the GHMBC experiment can complicate the interpretation of the data when dealing with novel chemical structures. A priori there is no way to differentiate 2J(CH) from (n)J(CH) correlations, where n ≥ 3. Access to high-field spectrometers with cryogenic NMR probes brings 1,1- and 1,n-ADEQUATE experiments into range for modest samples. Subjecting ADEQUATE spectra to covariance processing with high sensitivity experiments such as multiplicity-edited GHSQC affords a diagonally symmetric 13C-13C correlation spectrum in which correlation data are observed with the apparent sensitivity of the GHSQC spectrum. HSQC-1,1-ADEQUATE covariance spectra derived by co-processing of GHSQC and 1,1-ADEQUATE spectra allow the carbon skeleton of molecules to be conveniently traced. HSQC-1,n-ADEQUATE spectra provide enhanced access to correlations equivalent to 4J(CH) correlations in a GHMBC spectrum. When these data are used to supplement GHMBC data, a powerfully synergistic set of heteronuclear correlations are available. The methods discussed are illustrated using retrorsine (1) as a model compound.
    Journal of Natural Products 11/2011; 74(11):2400-7. · 3.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Long-range, two-dimensional heteronuclear shift correlation NMR methods play a pivotal role in the assembly of novel molecular structures. The well-established GHMBC method is a high-sensitivity mainstay technique, affording connectivity information via (n)J(CH) coupling pathways. Unfortunately, there is no simple way of determining the value of n and hence no way of differentiating two-bond from three- and occasionally four-bond correlations. Three-bond correlations, however, generally predominate. Recent work has shown that the unsymmetrical indirect covariance or generalized indirect covariance processing of multiplicity edited GHSQC and 1,1-ADEQUATE spectra provides high-sensitivity access to a (13)C-(13) C connectivity map in the form of an HSQC-1,1-ADEQUATE spectrum. Covariance processing of these data allows the 1,1-ADEQUATE connectivity information to be exploited with the inherent sensitivity of the GHSQC spectrum rather than the intrinsically lower sensitivity of the 1,1-ADEQUATE spectrum itself. Data acquisition times and/or sample size can be substantially reduced when covariance processing is to be employed. In an extension of that work, 1,n-ADEQUATE spectra can likewise be subjected to covariance processing to afford high-sensitivity access to the equivalent of (4)J(CH) GHMBC connectivity information. The method is illustrated using strychnine as a model compound.
    Magnetic Resonance in Chemistry 09/2011; 49(10):641-7. · 1.53 Impact Factor
  • Gary E Martin, Bruce D Hilton, Kirill A Blinov
    [Show abstract] [Hide abstract]
    ABSTRACT: Various experimental methods have been developed to unequivocally identify vicinal neighbor carbon atoms. Variants of the HMBC experiment intended for this purpose have included 2J3J-HMBC and H2BC. The 1,1-ADEQUATE experiment, in contrast, was developed to accomplish the same goal but relies on the (1) J(CC) coupling between a proton-carbon resonant pair and the adjacent neighbor carbon. Hence, 1,1-ADEQUATE can identify non-protonated adjacent neighbor carbons, whereas the 2J3J-HMBC and H2BC experiments require both neighbor carbons to be protonated to operate. Since 1,1-ADEQUATE data are normally interpreted with close reference to an HSQC spectrum of the molecule in question, we were interested in exploring the unsymmetrical indirect covariance processing of multiplicity-edited GHSQC and 1,1-ADEQUATE spectra to afford an HSQC-ADEQUATE correlation spectrum that facilitates the extraction of carbon-carbon connectivity information. The HSQC-ADEQUATE spectrum of strychnine is shown and the means by which the carbon skeleton can be conveniently traced is discussed.
    Magnetic Resonance in Chemistry 03/2011; 49(5):248-52. · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Utilizing (13)C-(13)C connectivity networks for the assembly of carbon skeletons from HSQC-ADEQUATE spectra was recently reported. HSQC-ADEQUATE data retain the resonance multiplicity information of the multiplicity-edited GHSQC spectrum and afford a significant improvement in the signal-to-noise (s/n) ratio relative to the 1,1-ADEQUATE data used in the calculation of the HSQC-ADEQUATE spectrum by unsymmetrical indirect covariance (UIC) processing methods. The initial investigation into the computation of HSQC-ADEQUATE correlation plots utilized overnight acquisition of the 1,1-ADEQUATE data used for the calculation. In this communication, we report the results of an investigation of the reduction in acquisition time for the 1,1-ADEQUATE data to take advantage of the s/n gain during the UIC processing to afford the final HSQC-ADEQUATE correlation plot. Data acquisition times for the 1,1-ADEQUATE spectrum can be reduced to as little as a few hours, while retaining excellent s/n ratios and all responses contained in spectra computed from overnight data acquisitions. Concatenation of multiplicity-edited GHSQC and 1,1-ADEQUATE data also allows the interrogation of submilligram samples with 1,1-ADEQUATE data when using spectrometers equipped with 1.7-mm Micro CryoProbes ™.
    Magnetic Resonance in Chemistry 03/2011; 49(6):350-7. · 1.53 Impact Factor
  • B. D. Hilton, W. Feng, G. E. Martin
    Journal of Heterocyclic Chemistry. 01/2011; 48:948-951.
  • G. E. Martin, B. D. Hilton, K. A. Blinov
    Magnetic Resonance in Chemistry. 01/2011; 49(5):248-252.
  • Magnetic Resonance in Chemistry. 01/2011; 49:641-647.
  • Source
    G. E. Martin, B. D. Hilton, K. A. Blinov
    Magnetic Resonance in Chemistry. 01/2011; 49:249-252.
  • G. E. Martin, B. D. Hilton, K. A. Blinov
    J. Nat. Prod. 01/2011; 74(11):2400-2407.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Long-range (1)H-(15)N heteronuclear shift correlation experiments at natural abundance are becoming more routinely utilized in the characterization of unknown chemical structures from a diverse range of sources including natural products and pharmaceuticals. Apart from the inherent challenges of the low gyromagnetic ratio and natural abundance of (15)N, investigators are also occasionally hampered by having to deal with the wide spectral range inherent to various nitrogen functional groups, which can exceed 500 ppm. Earlier triple resonance cryoprobe designs typically provided 90° (15)N pulses in the range of 35-40 µs, which did not allow the uniform excitation of wide F(1) spectral ranges for (1)H-(15)N GHMBC spectra. We report the results obtained with a newly designed Bruker 600 MHz triple resonance TCI Micro CryoProbe™ using methyl orange as a model compound, in which the (15)N resonances are separated by >450 ppm.
    Magnetic Resonance in Chemistry 12/2010; 48(12):935-7. · 1.53 Impact Factor
  • Bruce D Hilton, Gary E Martin
    [Show abstract] [Hide abstract]
    ABSTRACT: Practical experimental performance limits for an ensemble of heteronuclear 2D NMR experiments using a state-of-the-art 600 MHz 1.7 mm Bruker TCI Micro CryoProbe are reported. In the specific case of multiplicity-edited GHSQC, it was possible to acquire data on a 540 ng sample of strychnine (1; ∼1.6 nmol), prepared by serial dilution, which was used as a model compound. The experiments discussed also included GCOSY, (13)C reference spectra, (1)H-(13)C GHMBC, IDR-GHSQC-TOCSY, 1,1-ADEQUATE, and (1)H-(15)N GHMBC.
    Journal of Natural Products 09/2010; 73(9):1465-9. · 3.29 Impact Factor
  • Magnetic Resonance in Chemistry. 01/2010; 48(12):935-937.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Long-range homonuclear coupling pathways can be observed in COSY or GCOSY spectra by the acquisition of spectra with larger numbers of increments of the evolution period, t(1), than would normally be used. Alternatively, covariance processing of COSY-type spectra acquired with modest numbers of t(1) increments, allows the observation of multistage correlations. In this work results obtained from covariance-processed GCOSY spectra are fully analyzed and compared to normally processed COSY and 80 ms TOCSY spectra. Multistage or 'RCOSY-type' correlations are observed when remote protons both exhibit correlations to the same coupling partner e.g. A --> B and B --> C gives rise to an A --> C correlation. In the strict sense, RCOSY-type responses are artifacts albeit providing useful information. Nonbeneficial artifact correlations are observed when protons couple to other protons that overlap or partially overlap. The origin of artifact responses is also analyzed.
    Magnetic Resonance in Chemistry 10/2008; 46(11):997-1002. · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent reports have demonstrated the unsymmetrical indirect covariance combination of discretely acquired 2D NMR experiments into spectra that provide an alternative means of accessing the information content of these spectra. The method can be thought of as being analogous to the Fourier transform conversion of time domain data into the more readily interpreted frequency domain. Hyphenated 2D-NMR spectra such as GHSQC-TOCSY, when available, provide an investigator with the means of sorting proton-proton homonuclear connectivity networks as a function of the 13C chemical shift of the carbon directly bound to the proton from which propagation begins. Long-range heteronuclear chemical shift correlation experiments establish proton-carbon correlations via heteronuclear coupling pathways, most commonly across three bonds (3JCH), but in more general terms across two (2JCH) to four bonds (4JCH). In many instances 3JCH correlations dominate GHMBC spectra. We demonstrate in this report the improved visualization of 2JCH and 4JCH correlations through the unsymmetrical indirect covariance processing of GHSQC-TOCSY and GHMBC 2D spectra.
    Journal of Heterocyclic Chemistry 07/2008; 45(4). · 1.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several groups of authors have reported studies in the areas of indirect and unsymmetrical indirect covariance NMR processing methods. Efforts have recently focused on the use of unsymmetrical indirect covariance processing methods to combine various discrete two-dimensional NMR spectra to afford the equivalent of the much less sensitive hyphenated 2D NMR experiments, for example indirect covariance (icv)-heteronuclear single quantum coherence (HSQC)-COSY and icv-HSQC-nuclear Overhauser effect spectroscopy (NOESY). Alternatively, unsymmetrical indirect covariance processing methods can be used to combine multiple heteronuclear 2D spectra to afford icv-13C-15N HSQC-HMBC correlation spectra. We now report the use of responses contained in indirect covariance processed HSQC spectra as a means for the identification of artifacts in both indirect covariance and unsymmetrical indirect covariance processed 2D NMR spectra.
    Magnetic Resonance in Chemistry 02/2008; 46(2):138-43. · 1.53 Impact Factor
  • Journal of Heterocyclic Chemistry. 01/2008;
  • Magnetic Resonance in Chemistry. 01/2008;