When we undertook the work to write a review article on CASE Systems (computer-assisted structure elucidation) at the invitation of the Progress in NMR Spectroscopy editors we didn’t envisage almost 2 years of work. Adding a review article into an 80 hour work week, balancing with family, blah, blah, blah wasn’t quite sane. By the end it went from a labor of love to a burden. However, the last pangs of pain all washed away tonight when we heard that it’s online

Computer-assisted Structure Verification and Elucidation Tools In NMR-Based Structure Elucidation (Reference: JPNMRS1239) in Progress in Nuclear Magnetic Resonance Spectroscopy is alive and well and living at http://dx.doi.org/10.1016/j.pnmrs.2007.04.003.

For those of you who have been watching the hexacyclinol controversy (1,2,3,4,5,6) we just worked with John Porco’s group and used a CASE approach to generate the correct assignments for the molecule. The work is presently being submitted for publication under the following abstract.

“Computer-Assisted Structure Elucidation (CASE) using a combination of 1D and 2D NMR data has been available for a number of years. These software programs can be considered as logic machines capable of deriving all plausible structures from a set of structural constraints or “axioms”, these being produced from the spectral data and associated chemical information or prior knowledge. CASE programs allow the spectroscopist not only to determine the structures from the spectral data but also to study the dependence of the solution on changes to the set of axioms. In this article we describe the application of the ACD/Structure Elucidator expert system to resolve the conflict between two different hypothetical hexacyclinol structures derived by different researchers from the NMR spectra of this complex natural product. It has been shown that the combination of algorithms for both structure elucidation and structure validation delivered by the expert system enables the identification of the most probable structure as well as the associated chemical shift assignment.”

The final assignments are shown below, together with some of the correlations used to generate the assignment.

Hexacyclinol

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3 Responses to “Almost 2 Years in the Making – A Review Article on Computer Assisted Structure Elucidation: Assigning the Structure of Hexacyclinol”

  1. Ryan's Blog on NMR Software says:

    Another Article! Also, the Hexacyclinol Debate

    OK, if you don’t know it by now Antony J. Williams, M.E. Elyashberg, and Gary E. Martin are publication writing machines. On the Chemspider Blog, Tony points us to their latest publication (reportedly 2 years in the making) that is

  2. Computational Organic Chemistry » Predicting the Structure of Hexacyclinol says:

    [...] As an alternative, Rychnovsky proposed that hexacyclinol is in fact the by-product from work-up of the natural product panepophenanthrin, also obtained from Panus rudis. He proposed that hexacylinol has the structure shown in 5. He optimized the geometry of 5 and obtained two low-energy conformers. The second-lowest conformer, shown in Figure 3, has a predicted 13C NMR spectrum in very close agreement with experiment. Its average chemical shift deviation is 1.8 ppm with a maximum difference of 5.8 ppm. These differences are consistent with those found in the diterpenes test set. This structure has now been synthesized by Porco and its x-ray structure obtained.5 This compound has the structure predicted by Rychnovsky and is completely consistent with the original hexacyclinol compound reported by Gräfe. This successful resolution of the structure of hexacycliinol should spur further use of computational methods to predict NMR spectra and evaluate chemical structures. ACD has recently applied its method for predicting NMR spectra to the problem of hexacylinol.6 You can read about this on the ChemSpider blog. [...]

  3. The Full NMR Assignment of Hexacyclinol using CASE now published at The ChemConnector Blog - Observations and Musings for the Chemistry Community says:

    [...] on a number of blogs and has caused a furor within the organic chemistry community. I have discussed this previously on the ChemSpider blog. Well, I am happy to say that the article describing our work is finally available as an ASAP [...]

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