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More Comments About Diazonamide A – other efforts to distinguish WHAT’S REAL?

24 Sep

Following on from my posting last night about Diazonamide A I note that PMR has blogged about this. Peter’s conclusion was that “the blogosphere is starting to emerge as a serious place to look for chemistry.” I have to agree! Just Paul’s one posting on Diazonamide A has resulted in a lot of additional trackbacks!

 I want to comment on a few of Peter’s comments and offer additional commentary. Before proceeding browse his posting then return back here.

Some comments…

1) regarding the structure on PubChem Peter commented “Lovely. I think it’s correct, but it’s not exactly beautiful.” As I commented in my previous posting…there are TWO structures on PubChem. They are DIFFERENT..check the InChI. It is why they are not deduplicated. And those structures ARE very ugly so there is no way to consider the stereochemistry other than downloading the molfile and cleaning it locally hoping there isn’t a problem in the process!

2) Peter comments “So, off to chemspider which is free….<> There are two more structures but both are  equally unreadable”. yes absolutely. There has been a lot of commentaries about PubChem being the standard on many blogs so we did NOT clean the 2D structures when we loaded the PubChem dataset. These coordinates are exactly as downloaded from PubChem. We are working on improving these displays by working with a collaborator to source a new CLEANing algorithm.

3) Peter comments “I try to zoom the formula and get a featureless gray square on both IE and Firefox.” There are six structures in the search. 350562, 4591072, 10472888, 10478902, 17209260, 17212293. The first four show nice ZOOMed structure images. The last two don’t. Why? The database has just been updated to about 18.5 Million structures, an additional 2 million structures in the past couple of weeks. We are presently deduplicating an additional few million structures and will likely cross 20 million structures by the end of the week. The structure IMAGES have not yet been added for the latest additions. They will appear in the near future following the next deduplication process.

4) Peter comments “So I try Jmol (shown right). Now the molecules are three-dimensional but the coordinates in chemspider are those of the 2-D diagram. Personally I regard this as extremely misleading and would NEVER use Jmol for 2D diagrams, but I shan’t pursue this here.”

We’ve commented on this already on this blog. We have been sourcing a 3D optimizer since PubChem does not provide 3D coordinates. We have one now…more comments will come shortly. We probably have over 20 million structures to optimize and, of course, limited resources. So, we’ll get to this when we get to it. We’re leaving Jmol in place until structures are optimized.  I encourage you all to add yourselves to the Feedburner signin on the blogs to stay informed. We don’t intentionally mislead…

 5) Peter comments ”

So I still don’t know what the molecule is. Where else? Perhaps I can use some more abstracts…And the fourth one on Pubmed hits gold. It’s from PNAS:” Also:

 Diazonamide entry

The comment “I’m sure it’s correct” is interesting. ESPECIALLY since the structure has been revised by Harrans’ group (J. Li, S. Jeong, L. Esser and P. G. Harran, Angew. Chem., Int. Ed.,2001, 40, 4765). Is the paper in PNAS for the original structure or the revised structure? it’s from February of this year so in this case I think Peter is correct. But you get the point …you just have to consider the hexacyclinol debacle to realize that what is printed for a structure is not necessarily correct.

In fact, my own belief is that while the structure is the best representation of the structure lots of errors are made in drawing them – stereocenters are omitted, the structures are drawn in a visually appealing form and sometimes actually misrepresent the structure and cause changes in stereochemistry especially with double bond orientiation. The structure editor used for drawing should be used to generate the details of the stereocenters and they should then be reviewed for accuracy before accepting the structure representation (and generating InChIs etc)

Recently we announced that we had acquired ChemRefer and that we were going to benefit from the closer relationship! However, even now it is possible to use ChemRefer to search articles and so a search for Diazonamide A on ChemRefer found 6 hits as shown below.

ChemRefer and Diazonamide

 Beautiful structures are just a click away. Some are shown below…all supposed to be Diazonamide A.

Hot off the press (Nat. Prod. Rep., 2004, 21, H23) – Royal Society of Chemistry

NPR review

Another_One_Is_Shown_Here: 4 Total synthesis highlights (Annu. Rep. Prog. Chem., Sect. B: Org. Chem., 2004, 100, 91) – Royal Society of Chemistry

 Total Synthesis Highlights

Tandem reactions, cascade sequences, and biomimetic strategies in total synthesis (Chem. Commun., 2003, 551) – Royal Society of Chemistry

Chem Commun

 

Anyways…you get the point. PDF files with direct information about Diazonamide A are one click away on ChemSpider through the integrated ChemRefer service. Overall I would say that the structure drawn by Paul Docherty on the TotallySynthetic Blog is CONSISTENT with that given in Simple indole alkaloids and those with a nonrearranged monoterpenoid unit (Nat. Prod. Rep., 2004, 21, 278) – Royal Society of Chemistry so maybe the case is closed. With this information in hand I look forward to a definitive statement from the expert synthetic chemists so that we can make sure the CORRECT structure for Diazonamide A is on ChemSpider.

 

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 24, 2007 in Uncategorized

 

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