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Will the Correct Structure of Taxol Please Stand Up. Part 2.

25 Sep

I covered the issue of taxol a few weeks ago: http://www.chemspider.com/blog/?p=64. Today Taxol came up again on a post by Peter Murray-Rust. First of all a couple of comments re the post.

PMR commented “The intelligible Chemspider image was hand-drawn by the PNAS authors – I don’t know how it got to Chemspider. (Personally I think it’s pretty awful – I do not like stereo bonds which are rectangular rather than wedges. Why do people use them. And You only have to scale the image to corrupt this info). So we need an Open collection of chemical structures.” In case there is confusion please read the original post…the structure was grabbed from a PDF file (4 Total synthesis highlights (Annu. Rep. Prog. Chem., Sect. B: Org. Chem., 2004, 100, 91) – Royal Society of Chemistry)…it is NOT on ChemSpider. The structure was located by a search using Chemrefer, now on ChemSpider. It was not drawn by us, we’re not responsible for it and, to clarify, I don’t like it either.

Oh, and we do have an Open Collection of chemical structures. The deposition process is under beta-testing and anyone can download the data (we will give away the entire structure collection shortly).

Peter commented that Wikipedia is highly curated. I use it a lot. But, I am cautious…ESPECIALLY with stereochemisty. I’m trying to determine what the ACTUAL taxol structure is. My investigations suggest that one stereocenter is WRONG on the Wikipedia structure. The link to the PubChem record is therefore to the incorrect structure in theory.

Also, the systematic name is not what I would term as anywhere near IUPAC standard: β-(benzoylamino)-α-hydroxy-,6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)
oxet-9-ylester,(2aR-(2a-α,4-β,4a-β,6-β,9-α(α-R*,β-S*),11-α,12-α,12a-α,2b-α))-benzenepropanoic acid

By the way…the name on Drugbank is 5 beta,20-Epoxy-1,2a,4,7 beta,10 beta,13 alpha-hexahydroxytax-11-en-9-one 4,10-diacetate
2-benzoate 13-ester with (2 R,3S)-N-benzoyl-3-phenylisoserine….hmmm…

I would LOVE this post to get confirmation regarding what the right structure is…is Wikipedia CORRECT or Wrong? I THINK the structure on Drugbank is RIGHT. This DIFFERS from the Wikipedia structure by one stereocenter. Check out the InChIs below:

PUBCHEM
InChI=1/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37-,38-,40-,45+,46-,47+/m0/s1/f/h48H

DRUGBANK
InChI=1/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+/m0/s1/f/h48H

Compare the STEREO layer at:
t31-,32-,33+,35-,36+,37-,38-,40-,45+,46-,47+
t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+

and compare the stereo for stereo center 37… one is PLUS and one is MINUS. OOPS!

I’m certainly willing to be wrong but the point is, right now, I am not sure what the right structure. Can anyone out there confirm??? Can someone check “the” highly curated data source and tell us?

Until then I am in full agreement with Peter regarding what Wikipedia SHOULD be “It’s Open, re-usable, very highly curated, and the first place that students look. That – or a derivative – is where the world’s chemistry should reside. ” HOWEVER, I am calling for confirmation of the structure and correction if necessary. One of either DrugBank OR PubChem, both linked from Wikipedia, is wrong.

In terms of the comment “That – or a derivative – is where the world’s chemistry should reside”. I DO agree. We have committed to a wiki-environment for Chemistry. We are presently deciding on the appropriate wiki environment (NOT necessarily MediaWiki) to layer onto ChemSpider. Email exchanges are underway with some of the players in this domain at present – and a sincere thanks to Joerg Wegner for his support on this! With Martin Walker on our advisory group (Walkerma on Wikipedia…a very active player in this domain) we look forward to the best advice and guidance from our collaborators.

 

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 September 25, 2007 in ChemSpider Chemistry

 

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