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Almost 2 Years in the Making – A Review Article on Computer Assisted Structure Elucidation: Assigning the Structure of Hexacyclinol

07 Jul

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

 

About tony

Antony (Tony) J. Williams received his BSc in 1985 from the University of Liverpool (UK) and PhD in 1988 from the University of London (UK). His PhD research interests were in studying the effects of high pressure on molecular motions within lubricant related systems using Nuclear Magnetic Resonance. He moved to Ottawa, Canada to work for the National Research Council performing fundamental research on the electron paramagnetic resonance of radicals trapped in single crystals. Following his postdoctoral position he became the NMR Facility Manager for Ottawa University. Tony joined the Eastman Kodak Company in Rochester, New York as their NMR Technology Leader. He led the laboratory to develop quality control across multiple spectroscopy labs and helped establish walk-up laboratories providing NMR, LC-MS and other forms of spectroscopy to hundreds of chemists across multiple sites. This included the delivery of spectroscopic data to the desktop, automated processing and his initial interests in computer-assisted structure elucidation (CASE) systems. He also worked with a team to develop the worlds’ first web-based LIMS system, WIMS, capable of allowing chemical structure searching and spectral display. With his developing cheminformatic skills and passion for data management he left corporate America to join a small start-up company working out of Toronto, Canada. He joined ACD/Labs as their NMR Product Manager and various roles, including Chief Science Officer, during his 10 years with the company. His responsibilities included managing over 50 products at one time prior to developing a product management team, managing sales, marketing, technical support and technical services. ACD/Labs was one of Canada’s Fast 50 Tech Companies, and Forbes Fast 500 companies in 2001. His primary passions during his tenure with ACD/Labs was the continued adoption of web-based technologies and developing automated structure verification and elucidation platforms. While at ACD/Labs he suggested the possibility of developing a public resource for chemists attempting to integrate internet available chemical data. He finally pursued this vision with some close friends as a hobby project in the evenings and the result was the ChemSpider database (www.chemspider.com). Even while running out of a basement on hand built servers the website developed a large community following that eventually culminated in the acquisition of the website by the Royal Society of Chemistry (RSC) based in Cambridge, United Kingdom. Tony joined the organization, together with some of the other ChemSpider team, and became their Vice President of Strategic Development. At RSC he continued to develop cheminformatics tools, specifically ChemSpider, and was the technical lead for the chemistry aspects of the Open PHACTS project (http://www.openphacts.org), a project focused on the delivery of open data, open source and open systems to support the pharmaceutical sciences. He was also the technical lead for the UK National Chemical Database Service (http://cds.rsc.org/) and the RSC lead for the PharmaSea project (http://www.pharma-sea.eu/) attempting to identify novel natural products from the ocean. He left RSC in 2015 to become a Computational Chemist in the National Center of Computational Toxicology at the Environmental Protection Agency where he is bringing his skills to bear working with a team on the delivery of a new software architecture for the management and delivery of data, algorithms and visualization tools. The “Chemistry Dashboard” was released on April 1st, no fooling, at https://comptox.epa.gov, and provides access to over 700,000 chemicals, experimental and predicted properties and a developing link network to support the environmental sciences. Tony remains passionate about computer-assisted structure elucidation and verification approaches and continues to publish in this area. He is also passionate about teaching scientists to benefit from the developing array of social networking tools for scientists and is known as the ChemConnector on the networks. Over the years he has had adjunct roles at a number of institutions and presently enjoys working with scientists at both UNC Chapel Hill and NC State University. He is widely published with over 200 papers and book chapters and was the recipient of the Jim Gray Award for eScience in 2012. In 2016 he was awarded the North Carolina ACS Distinguished Speaker Award.
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Posted by on July 7, 2007 in ChemSpider Chemistry

 

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