Author Archive

ChemSpider for natural product research – an introduction

This blog post is an introduction to a series that we will be running that looks at how natural products research can be facilitated by new technologies, such as ChemSpider. Along the way we might also consider some of the challenges that come with generating and (re)using chemical data as we move into an age where more and more data is generated by all of us, and the end consumer of that data may not only be a human reading a publication on a screen (or in a print copy).

In our recently published editorial we mention our belief that the natural products community may benefit from both using and contributing to ChemSpider. Over the next few posts we hope to illustrate some aspects of ChemSpider that we hope may be of use.

We don’t know if you use ChemSpider every day, or have only visited the site once or twice; if you always find what you want or perhaps have sometimes have obtained unexpected results; or somewhere in-between. But we hope that we can show you how features of ChemSpider that make your life easier, be it by showing you: types of data that you didn’t know that you could find; or approaches to searching that you were not aware of. Most of all, we hope that we can show you the possibility of the resource that we as a community of researchers passionate about chemical structures can build.

Of course we don’t want this to be a one-way conversation, and we welcome comments to the blog posts and emails (please direct these to ChemSpider@rsc.org in the first instance).

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Natural Product Updates – new site launched

Natural Product Updates has launched a new website with personalised alerts, to help you to find relevant articles even faster.

On the new platform subscribers can set up tailored email alerts and saved searches, saving time and bringing the latest developments directly to their inbox.

Our trained editors select the content from a wide range of primary sources. Each article is presented with a representative structure, and is also searchable by source organism, biological activity and compound type

Natural Product Updates is a literature alerting service keeping you current with the latest developments in natural product chemistry. It covers the isolation of new natural products, structure elucidation, synthesis, biosynthesis and biological activity studies. Reviews in all of these areas are also included.

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The Great Chemistry Bake-off

On Friday the 27th of February the final of the 2nd National Retrosynthesis Competition was held had at Burlington House. To read more about the event itself please see our post from two weeks ago.

In this blog we bring you thoughts on the experience from Stephen Penrose, Ph.D. a member of the winning team from Charles River Laboratories, 1ED.


At the end of an exciting but emotionally exhausting day at Burlington House the top three synthetic routes to Alistonitrine A were announced. In third place Manchester University, in second place Oxford University…

The consensus among Team 1ED was that our greatest competitors had placed second—did we have a chance? We had produced an excellent, novel synthesis backed up with solid literature precedent for all the steps, presented and defended with style and substance. Could we be picking up the beautifully crafted round-bottom flask trophy? When Charles River Early Discovery was announced in first place we were absolutely delighted. We were National Retrosynthesis champions for the next two years! The complex, team-based problem solving we use every day for confidential client programmes was there for all to see on a national stage.

To show the strength of synthetic chemistry in the UK, the Royal Society of Chemistry (RSC) and the Society of Chemical Industry (SCI) initiated the biennial National Retrosynthesis Competition. The contest is a great opportunity for young chemists (under the age of 35) from all areas of the chemistry community to test their skills in paper molecular deconstruction (and construction). The first competition was held in 2013, and the problem solving and synthetic complexity of the natural products showcased was highly impressive. As part of the newly formed Charles River Discovery Services unit we were very keen to showcase the quality of our synthetic talents and challenge ourselves against like-minded academic groups and industrial leaders in the 2015 competition. A team of eight was assembled from our Cambridge, Harlow and Welwyn Garden City sites and the first round target was disclosed. To quote from my biology colleagues, it was “a piece of cake”, but only if you were deconstructing, then constructing a 4-tier wedding cake without a recipe!

The qualifying target was the natural product Myrothecol A—a quinone sesquiterpene isolated from a leaf litter sample collected in Guangdong China. This compound has attractive biological activity against a range of targets including HIV, tuberculosis and immunosuppression. Working closely within our team we were able to produce six different synthetic routes to Myrothecol A. As a team we critically evaluated all the routes, and through a combination of ideas and literature precedent for each step we evolved our route. For our first round entry the CRL route to Myrothecol A had a longest linear sequence of 14 steps with an estimated overall yield of 3.2%.

For the final of the competition we were given a more complex product to dissect: Alistonitrine A. This compound is a metabolite from Alstonia scholaris R. Br.. The bark and leaves have been used as traditional medicines to treat a number of ailments, including dysentery, malaria, and chronic respiratory disease. The compound is very rare with 15 kg of air-dried leaves giving a mere 5 mg of Alistonitrine A.

Alistonitrine A

This molecular construction was also much more complex, due to the fact that nobody had previously made the compound (or anything similar). The team optimised every step of the synthesis to determine whether there was compatibility of functional groups and how to install the unprecedented 6,5,6,5,5,6 ring system containing 2 aminal bridges and 6 contiguous chiral centres. After numerous meetings and around 10 different routes being critically evaluated and discarded, we had a framework from which to proceed. The strategy we envisaged was based on Emil Fischer’s concept of asymmetric induction—using a single chiral centre to give preferential formation of all other chiral centres in the final structure.

To put the theory into practice we needed a very reliable method of forming the initial cage system (that’s the 6,5,5,6 part) and with excellent enantiomeric excess. With this in mind we decided to use the excellent methodology of Prof. David Macmillan—an organocatalytic endo [4+2] cyclisation. This route would give us the ideal start on the molecule. From this point onwards almost all of the steps were unprecedented to Alistonitrine A. The underpinning step to close most of the rings was a diastereoselective intramolecular 1,6 conjugate amidation of an acyl sulfamide into an α,β,γ,δ-unsaturated ester.

We needed a further degree of confidence that this would work successfully; did we have the right bond geometry for the transformation to work? Was the NH nucleophilic enough to react? In order to answer these questions we were guided by our excellent computational chemistry team. They provided us the tools we needed to produce an energy-minimised model to show that the acyl sulfamide was perfectly placed to undergo our bond forming reaction.

We also used in-house tools to calculate the pKa of the NH bond to give compelling evidence that we could form a suitable anion to undergo the ring closing process. This evidence supported our asymmetric induction approach and showed that we had a fighting chance of synthesising Alistonitrine A (on paper at least). We had turned a challenging synthetic competition into a multi-disciplinary team-based problem solving exercise using our colleagues at CRL.

Giving our clients the best possible outcomes is critical to us at CRL. Applying this same work ethic, we used not only our skills in problem solving, but our skills in presenting the data, which included an extensive set of back-up slides that helped us defend all of our steps.

Our final effort was to be judged at Burlington House (home of the Royal Society of Chemistry since 1841) by a panel of experts. Each of the 10 teams gave a 20-minute presentation followed by questions from both the judging panel as well as the audience.

As the penultimate team to compete we had watched a number of teams throughout the day, each producing thought provoking synthesis. One team had compared Alistonitrine A to Wembley football stadium. At 15:00 my colleague Joe Marshall and I were given the honour of upholding CRL’s reputation. There had been a number of practice talks and we had all the points clear in our minds and delivered them well. Time seemed to go very quickly. I spent most of my time watching our teammates on the floor; the nods, smiles and thumbs-ups really helped to quell any nerves. By the end of the 20 minutes we were delighted with what we had achieved—but then came the dreaded questioning!

During the course of the day the team had noticed that the questions seemed to be most fierce for teams that were felt to be top competition. We defended the first few questions well, but then a hand went up in the audience. “Great synthesis. I had a comment about your sulfamide bridge deprotection. I don’t think the step you proposed works, can you run me through it?” Sure, we thought going to our backup slides; here is the precedent… “But you need a free NH for that mechanism to work.”

I have to say I have never stood in front of the audience and heard such an audible groan of disappointment in my career! One part of me thought this was it, we were out of the running for the top prize. But another part of me thought that if I was presenting to a client I would defend my scientific opinion. I wanted CRL to look strong in front of our national peers so we continued the defence, answering questions about nucleophilicity of aminals over amines and whether our final ring-closing step would actually work. Thankfully, for every question asked we had back-up slides reinforcing our work. There were no further “banana skins” and we finished as we started, delivering and defending with style.

There was one more presentation to digest before the final deliberation from the judging panel. I felt absolutely drained. The extra hours and the trips up and down the country for face-to-face discussions had finally come to a thrilling conclusion. We had made a couple of minor mistakes in our synthesis, but we felt many teams had made more. Did we have an excellent synthesis? Had we defended our work to the best our ability? We thought so.

When we placed first there was a sense of jubilation that the team had managed to innovate and deliver better than some very prestigious competitors from industry and academia. At the post-competition mixer we were told by the judges that they struggled to split some of the synthesis as the general standard was excellent. What set the CRL team apart were our presentation skills, defence of the questions and the comprehensive literature work we had done.

It was pretty clear to me after the competition that complex, team-based problem solving is critical to everything we do in medicinal chemistry, from identifying and designing the compound to probing its pathways. The Retrosynthesis Competition crystallized this for me and demonstrated that great teamwork—and the pursuit of innovation and excellence that goes along with it—is the reason we strive to produce that novel compound which makes all the difference.

Senior scientist and medicinal chemist Stephen Penrose, Ph.D., is a member of Charles River’s winning 1ED team that competed recently in the National Retrosynthesis Competition.

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National Retrosynthesis Competition Final

On Friday the 27th of February, Burlington House was the venue for the final of the 2nd National Retrosynthesis Competition. This event was jointly organised by the Heterocyclic and Synthesis Group of the Royal Society of Chemistry, and the Fine Chemicals Group and Young Chemists Panel of the SCI, under the lead of Rob Wybrow of Syngenta, UK.

From 50 teams who entered the preliminary round in December 2014, 10 were selected for the final by the judging panel, Professor Chris Willis (Bristol University), Professor Rob Stockman (Nottingham University), Dr Wes Heaton (GSK) and Dr Mike Mortimore (Vertex). The finalists were drawn from a broad cross-section of chemistry-based organisations, universities and academic institutions, pharmaceutical companies, CROs and agrochemicals.

In the final, teams presented their synthetic strategies for the recently identified, as yet unsynthesized natural product, alistonitrine A, and answered questions from the audience challenging their reasoning and route selection. Trophies for the winning teams were generously provided by Chemglass Life Sciences, and the overall winners received an additional prize of a year’s subscription to Natural Product Reports, provided by the Royal Society of Chemistry.

The winning team “One ED”, representing Charles River Laboratories, received a Huber Unichiller 003-MPC (donated by Huber). The runners up were “Oxford SBM Team” from Oxford University who received a Flashforge Creator 3D Printer  (donated by Chemglass Life Sciences), and the third place on the podium was taken by “Team Dalton Towers” from the University of Manchester, who received a J Young 5 port Vacuum Manifold (donated by GPE).

The organising committee would like to thank all of the teams who entered for their contributions, the finalists, judges, guests, attendees, sponsors and exhibitors for their significant input into the event. Based upon enthusiastic positive feedback from participants and special guests on the day the competition was hugely successful, underlining the key central importance of synthetic organic chemistry in both fundamental and applied research in the UK. Taking that positive momentum forwards, the organising committee has already begun their planning for the 3rd National Retrosynthesis Competition, to be held in early March 2016.

Retrosynthesis winners “One ED” from Charles River Laboratories

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Agri Innovation 2015

Join us on 22 April at the Society of Chemical Industry in London for Agri Innovation 2015: Emerging Technologies in Crop Research

This one-day meeting aims to provide an update on several areas of crop research, including identifying target proteins for crop protection ingredients, the synthesis of new crop protection agents and understanding the mechanisms of resistance and immunity in plants and insects. If you are working in organic synthesis, chemical biology or biochemistry in relation to crop science, this meeting will provide an opportunity to catch up on the latest developments. Speakers from academia and industry from across Europe will come together to present and discuss the latest developments in this area.

The meeting is jointly run by the Royal Society of Chemistry, the Society of Chemical Industry Agrisciences Group and AGRI-net, the agriscience chemical biology network. For more details and to register, please visit the website.

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Editorial Board Changes

As the new year gets underway we would like to share some changes to our Editorial Board.

Editorial Board Retirements

After 6 years with Natural Product Reports we are very sorry to see Professors David L. Jakeman and Stefan Schulz step down from their roles on the Editorial Board. We would like to take this opportunity to thank both David and Stefan for all of their time and effort over the past 6 years, helping to make the journal the success it is today. Thank you!

However, we are pleased to say that although David and Stefan may be leaving the Editorial Board they will not be leaving us entirely. Both are now members of the Advisory Board for the journal and we look forward to continue working with them in the future in this new role.

Prof. David L. Jakeman

Prof. Stefan Schulz


New Editorial Board Members

We would also like to take this opportunity to welcome some new faces to the Natural Product Reports family.

Prof. Giovanni Appendino

Professor Giovanni Appendino, Universita del Piemonte Orientale, Italy.

Professor Giovanni Appendino did his Laurea Degree at the University of Torino (Italy) in 1979. He did Post-Laurea work at the Laboratory of Organic Synthesis, University of Gent (Belgium) with Prof. Pierre De Clercq. He has been a Full Professor of Organic Chemistry at the Università del Piemonte Orientale, Department of Pharmaceutical Sciences, Novara (Italy), since 2000.

Research activity in his laboratories takes inspiration from plant natural products to address problems in various realms of biomedical investigation, from pharmacology and nutrition (new drug leads and health-promoting dietary ingredients) to organic/medicinal chemistry (new synthetic methodologies and optimization of natural product drug leads) and cell biology (novel mechanisms of activity).



Prof. Mark Brönstrup

Professor Mark Brönstrup, Helmholtz Centre for Infection Research, Germany

Mark Brönstrup studied Chemistry at the Philipps-Universität Marburg and at the Imperial College in London. In 1999 he received his doctorate from the Technical University Berlin in Organic Chemistry. After his graduation, he worked from 2000 to 2004 as a laboratory head for Mass Spectrometry at Aventis, complemented by a research sabbatical in 2003 at Harvard Medical School. From 2005 to 2010 he led the Natural Product Sciences section at Sanofi-Aventis in Frankfurt with the goal of discovering leads from natural sources and optimising them to clinical candidates. He dealt with translational research projects from 2010 to 2013 as a section head for Biomarkers & Diagnostics in the Diabetes Division, and a domain head for Biomarkers, Bioimaging & Biological Assays at Sanofi. Since December 2013, he heads the department Chemical Biology at the Helmholtz Centre for Infection Research; additionally, he holds a Professorship (W3) at the Leibniz Universität Hannover.

Mark Brönstrup’s research uses chemical biology tools to understand mechanisms for the treatment of infectious diseases.



Professors Appendino and Brönstrup began their roles as Editorial Board members from January 2015, and we look forward to working closely with them over the coming months and years.

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Seth Herzon wins 2015 NPR Emerging Investigator Lectureship

Seth Herzon winner of the 2015 NPR Emerging Investigator LectureshipWe are delighted to announce that Professor Seth Herzon from Yale University (USA) is the winner of the 2015 NPR Emerging Investigator Lectureship.

The NPR Lectureship is an annual event which is held at an international meeting, the recipient being a researcher who has made a significant contribution to any natural products-related research in their early independent career.

The conference at which the lecture will be delivered will be announced in due course.

Read more on Seth’s research on the Herzon lab Homepage

Previous winners include:

Emily Balskus, Harvard University, USA (2014 winner)
Rebecca Goss, University of St Andrews, UK (2013 winner)
Dean Tantillo, UC Davis Chemistry, USA (2012 winner)

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Q2 Top Ten most accessed articles

During the months April – June 2014, the most downloaded Natural Product Reports articles were:

Explorations of fungal biosynthesis of reduced polyketides – a personal viewpoint
John C. Vederas
DOI: 10.1039/C4NP00091A

Microbial biosynthesis of medicinally important plant secondary metabolites
Myoung Chong Song, Eun Ji Kim, Eunji Kim, Kris Rathwell, Sang-Jip Nam and Yeo Joon Yoon
DOI: 10.1039/C4NP00057A

Marine natural products
John W. Blunt, Brent R. Copp, Robert A. Keyzers, Murray H. G. Munro and Michèle R. Prinsep
DOI: 10.1039/C3NP70117D

Natural product isolation – how to get from biological material to pure compounds
Franz Bucar, Abraham Wube and Martin Schmid
DOI: 10.1039/C3NP20106F

Fungal polyketide biosynthesis – a personal perspective
Thomas J. Simpson
DOI: 10.1039/C4NP00065J

Natural product synthesis in the age of scalability
Christian A. Kuttruff, Martin D. Eastgate and Phil S. Baran
DOI: 10.1039/C3NP70090A

Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs
Giovanni Appendino, Alberto Minassi and Orazio Taglialatela-Scafati
DOI: 10.1039/C4NP00010B

Thinking big about small beings – the (yet) underdeveloped microbial natural products chemistry in Brazil
Laura P. Ióca, Pierre-Marie Allard and Roberto G. S. Berlinck
DOI: 10.1039/C3NP70112C

Recent advances in deep-sea natural products
Danielle Skropeta and Liangqian Wei
DOI: 10.1039/C3NP70118B

Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature
Wilfred A. van der Donk et al.
DOI: 10.1039/C2NP20085F

Access to these articles is free until the end of October through a registered RSC account – click here to register for free

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RSC Organic Division Poster Symposium 2014

RSC Organic Division Poster Symposium 2014, headline sponsored by F. Hoffmann-La Roche, Ltd.

The poster symposium, for final year organic chemistry PhD students, will take place at The Royal Society of Chemistry, Burlington House, London on Monday 01 December 2014.

The symposium offers final year PhD students a chance to showcase their research to their peers, leading academics and industrial chemists, and is open to all branches of organic chemistry. The symposium has a tradition of being the most competitive and highly regarded organic chemistry symposium for PhD students in the UK and ROI and we would like to thank F. Hoffmann-La Roche, Ltd. for their generous support of the event.

There will be a first prize of £500, two runner-up prizes of £250, and a “selected by Industry Prize”. Industrial delegates will make this selection by considering the research’s potential for application in an industrial context; the winner will also receive a prize of £500.

Closing date for submissions is Wednesday 01 October 2014.
For more information and to submit your abstract go to http://rsc.li/organic-poster

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Make your journal work for you

Want to know about the latest research we publish in Natural Product Reports? Want to be told about upcoming themed issues, or the most read articles, or other journal news?

Here are a few ways you can stay in touch with us and all that is happening:

RSS Feed for Natural Product ReportsMost recent articles

Be informed about the latest articles published on our website by adding us to your RSS Feed.


Issue alerts

Sign-up to NPR issue alertsGet the table of contents of the latest issue of Natural Product Reports sent direct to you when we publish the issue.


News alerts

Register for NPR news alertsBy joining our news alerts we can let you know about:

  • Up-coming themed collections (print & electronic)
  • Top Ten most accessed articles
  • Changes to our Editorial Board
  • Important news for the journal


Twitter

Follow Natural Product Reports on twitter

We can also be found on Twitter @NatProdRep, add us and say hello.


And of course you can always come back to this blog to find out about our journal news.

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