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OBC prize winner at CRSI National Symposium

02 Aug 2016

Congratulations to the OBC poster prize winner at the 2016 CRSI National Symposium!

We were pleased to present the OBC poster prize to Mr. K. Rajasekhar from the group of T. Govindaraju at the Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore. Mr. K. Rajasekhar presented his work on ‘Rationally designed peptidomimetic modulators of AB toxicity and related oxidative stress in Alzheimer’s disease’ on which he also recently published a Feature Article in Chemical Communications.

The 19th CRSI National Symposium in Chemistry is the most important annual chemistry symposium in India and took place from 14-16 July 2016 at the University of North Bengal (NBU), India.

Read K. Rajasekhar’s recent Feature article in ChemComm:

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer’s disease
K. Rajasekhar, Malabika Chakrabarti and T. Govindaraju
Chem. Commun., 2015,51, 13434-13450

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RSC Organic Division Poster Symposium 2016

01 Aug 2016

This poster symposium for final year organic chemistry PhD students will take place at The Royal Society of Chemistry at Burlington House, in London, Monday 5 December 2016.

Abstract submission is now open!

The closing date for abstract submissions is Monday 3 October 2016. Get more information or submit an abstract now.

This symposium offers final year PhD students a chance to showcase their research to their peers, leading academics and industrial chemists. It is open to all branches of organic chemistry – in its broadest interpretation – and has a tradition of being the most competitive and highly-regarded organic chemistry symposium for PhD students in the UK and Ireland.

There will be a first prize of £500, two runner-up prizes, and a ‘selected by Industry’ prize. Industrial delegates will select this winner based on the potential for application in an industrial context.

We would like to thank F. Hoffmann-La Roche, Ltd. and our industry sponsors for their generous support of this event.

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‘Microbial protein targets: towards understanding and intervention’ meeting

04 Jul 2016

Microbial protein targets: towards understanding and intervention

14–16 September 2016, Durham, UK

This symposium will bring together leading expertise in protein structure determination, biochemical characterization and chemical biology to explore the most recent advances in the understanding of protein function and inhibition in microbial pathogens – both bacteria and parasites.

An exciting line-up of speakers will present their recent work in the area. Some of the confirmed speakers are:

Chris Abell University of Cambridge, UK
Gerald Spaeth Institut Pasteur, Paris, France
Ed Tate Imperial College London, UK
Maria Marco-Martin GSK Tres Contos, Spain

Take advantage of this opportunity to showcase your work alongside leaders in the field and submit an abstract for an oral or poster presentation today. Through generous sponsorship from the RSC Chemical Biology Interface Division and the BSP there are bursaries available for early career researchers to support their participation at this meeting.

The oral abstract deadline has just been extended until 15 July 2016, and poster abstracts are welcome until 5 August 2016. For more information and to register please visit the conference webpage.

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New Editorial and Advisory Board Members

29 Jun 2016

We are very pleased to welcome two new members to our Organic & Biomolecular Chemistry Editorial Board and two new members to our Advisory Board – Dr Géraldine Masson (Institut de Chimie des Substances Naturelles, France) and Professor Govindasamy Mugesh (Indian Institute of Science, Bangalore, India), and Dr Gonçalo Bernardes (University of Cambridge, UK) and Dr Ratmir Derda (University of Alberta, Canada).

Géraldine Masson received her PhD in 2003 from the Joseph Fourier University, (France), under the supervision of Dr. Sandrine Py and Prof. Yannick Vallée. In the years 2003–2005 she was a Marie Curie postdoctoral research fellow with Prof. Jan van Maarseveen and Prof. Henk Hiemstra at the University of Amsterdam (Holland). In 2005, she joined the Institut de Chimie des Substances Naturelles (CNRS, France) as Chargé de Recherche and was promoted to Director of Research 2nd class in 2014. Her group’s research activities are directed toward the development of new organocatalytic enantioselective reactions and novel synthetic methodologies, and photoredox catalysis and their application in the synthesis of diverse natural and unnatural molecules displaying biologically activities.

Mugesh received his B.Sc. (1990) and M.Sc. (1993) degrees from the University of Madras and Bharathidasan University, respectively. He obtained his Ph.D. (1998) at the Indian Institute of Technology, Bombay. He was an Alexander von Humboldt Fellow at the Technical University, Braunschweig, Germany and a Skaggs postdoctoral fellow at the Scripps Research Institute, La Jolla, USA. Mugesh is an author of more than 120 publications in international peer reviewed journals. He received several awards and recognitions, which include: J. C. Bose National Fellowship, Government of India (2016); Asian Rising Star Commemorative Plaque, Asian Chemical Congress (2013), Fellow, Royal Society of Chemistry (FRSC, 2013), Shanti Swarup Bhatnagar Prize (2012), Fellow, The National Academy of Sciences, India (2012), AstraZeneca Excellence in Chemistry Award (2012); Fellow, Indian Academy of Sciences (2012); Swarnajayanti Fellowship, Government of India (2006-07).

His research interests include:

chemistry of thyroid hormone metabolism,
development of novel therapeutics for endothelial dysfunction and neurodegenerative diseases, and
nanomaterials for biological applications.

Gonçalo Bernardes graduated in Chemistry from the University of Lisbon in 2004 and soon moved to the University of Oxford where he completed his D.Phil. in 2008 under the supervision of Prof. Ben Davis. He was then awarded a Marie-Curie Fellowship to perform postdoctoral studies with Prof. Peter H. Seeberger. After a short period in Portugal working as a Group Leader at Alfama Lda., Gonçalo moved to the ETH Zürich to join the lab of Prof. Dario Neri. Gonçalo started his independent research career in 2013 at the Department of Chemistry, University of Cambridge after being awarded a prestigious Royal Society University Research Fellowship. Simultaneously, he founded a pioneering research unit in Chemical Pharmacology at the Instituto de Medicina Molecular in Lisbon. Despite his early age, he has published >50 papers and 5 patents. He has picked many accolades during his research career such as the European Young Chemist Award – Silver Medal in 2014, and more recentlythe Chem Soc Rev Emerging Investigator Lectureship 2016 and the RSC Harrison–Meldola Memorial Prize. For his efforts in translational research, Gonçalo was distinguished by the Portuguese Ministry of Health (MH) of Portugal for relevant services to Public Health and Medicine.

He now spends his time between his labs in Cambridge and Lisbon, directing a research program at the interface of chemistry and biology with a focus on the development of novel chemoselective reactions for the modification of biomolecules, and their use to understand and influence human disease.

Ratmir Derda received his undergraduate degree in Physics from Moscow Institute of Physics and Technology in 2001 and Ph.D. in Chemistry from the University of Wisconsin-Madison in 2008, under the supervision of Laura L. Kiessling. From 2008 to 2011, he was a postdoctoral researcher at Harvard University working under the supervision of George M. Whitesides and Donald E. Ingber. He joined University of Alberta in 2011 as an Assistant Professor in Chemistry and the Principal Investigator at the Alberta Glycomics Centre.

The Derda Lab centers on the development and mechanistic investigation of chemical transformations of genetically-encoded substrates. We employ genetically-encoded chemical libraries to attack unsolved problems in molecular recognition to aid the discovery of new therapeutics, biomaterials and molecular diagnostics.

Find some of their most recent RSC publications below or find out more about the other members of our Editorial and Advisory Boards here.

Catalytic, highly enantioselective, direct amination of enecarbamates
Audrey Dumoulin, Claudia Lalli, Pascal Retailleau and Géraldine Masson
Chem. Comm. , 2015, 51 , 5383-5386, DOI: 10.1039/C4CC08052A, Communication

One pot and selective intermolecular aryl- and heteroaryl-trifluoromethylation of alkenes by photoredox catalysis
Aude Carboni, Guillaume Dagousset, Emmanuel Magnier and Géraldine Masson
Chem. Comm. , 2014, 50 , 14197-14200, DOI: 10.1039/C4CC08052A, Communication

Insights into the catalytic mechanism of synthetic glutathione peroxidase mimetics
Debasish Bhowmick and Govindasamy Mugesh
Org. Biomol. Chem. , 2015, 13, 10262-10272, DOI: 10.1039/C5OB01665G, Review Article

Introduction of a catalytic triad increases the glutathione peroxidase-like activity of diaryl diselenides
Debasish Bhowmick and Govindasamy Mugesh
Org. Biomol. Chem., 2015, 13, 9072-9082, DOI: 10.1039/C5OB01294E, Paper

Iminoboronates are Efficient Intermediates for Selective, Rapid and Reversible N-Terminal Cysteine Functionalisation
Hélio Faustino, Maria José Silva, Luis F. Veiros, Gonçalo J. L. Bernardes and Pedro M. P. Gois
Chem. Sci., 2016, Accepted Manuscript, DOI: 10.1039/C6SC01520D, Edge Article

Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents
Tiago Rodrigues, Florian Sieglitz and Gonçalo J. L. Bernardes
Chem. Soc. Rev., 2016, Advance Article, DOI: 10.1039/C5CS00916B, Tutorial Review

Phage-displayed macrocyclic glycopeptide libraries
Simon Ng and Ratmir Derda
Org. Biomol. Chem., 2016, 14, 5539-5545, DOI: 10.1039/C5OB02646F, Communication

Heat-enhanced peptide synthesis on Teflon-patterned paper
Frédérique Deiss, Yang Yang, Wadim L. Matochko and Ratmir Derda
Org. Biomol. Chem., 2016, 14, 5148-5156, DOI: 10.1039/C6OB00898D, Paper

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16th French-American Chemical Society meeting

07 Apr 2016

French-American Chemical Society
16th Meeting

19-23 June 2016 – Santa Barbara, California, USA

Organic & Biomolecular Chemistry and Catalysis Science & Technology are delighted to support the 16th French-American Chemical Society meeting. The conference will feature an excellent range of speakers including:

Dennis Hall (University of Alberta) – Studies Towards the Synthesis of Polycyclic Alkaloids
Bastien Nay (Muséum National d’Histoire Naturelle) – Bio-inspired Strategies for the Total Synthesis of Polycyclic Chalasins and Related PKS-NRPS Natural Products
Surya Prakash (USC) – Our Recent Studies on Fluoroalkylations
David Williams (Indiana University) – Studies Towards the Synthesis of Polycyclic Alkaloids, and
Françoise Colobert (Université de Strasbourg) – Enantiopure Sulfoxide, an Efficient Chiral Directing Group for Stereoselective C-H Bond Activation.

Register now to secure your place and take part in this great five day symposium with 20 speakers comprising established and emerging researchers from both academia and industry. The meeting is organised by Professor Bruce Lipshutz (University of California Santa Barbara), Dr Robert Dodd (Institut de Chimie des Substances Naturelles) and Dr Jean Suffert (Université de Strasbourg) this year.

For more information and to book your place please visit the event page.

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Poster Prize winner at the University of California Symposium for Chemical Sciences

31 Mar 2016

Congratulations to the Poster Prize winner at the University of California Symposium for the Chemical Sciences.

Bryn Taylor (right) with Jennifer Griffiths from the RSC (photo courtesy of Beverly Chou from the Shea group)

The winner is Bryn Taylor of UC San Diego who is currently working as a graduate student in the group of Rob Knight and co-advised by Rommie Amaro. Her research encompasses computational chemistry and biophysics, focusing on microbial proteomes and the function of the microbiome.

The meeting took place for the first time and was supported by eight UC departments (UC Davis, UCLA, UC San Diego, UC Berkeley, UC Riverside, UC Santa Cruz, UC Irvine, UC Santa Barbara). All areas of chemistry, including biological, organic, inorganic, analytical and physical chemistry were represented and the symposium provided an excellent opportunity for graduate students and postdocs to not only present their work in a multidisciplinary environment, but also take part in different workshops to further their career and establish connections with professionals from industry, government and alternative science jobs.

The prize was presented by the RSC Editorial Development Manager, North America, Dr Jennifer Griffiths.

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Developing a fragment-based design-friendly methodology

10 Feb 2016

Target-based approaches to drug discovery have dominated pharmaceutical research since the early 1990s because they allow for increased screening capacity and rational drug design. Advances in combinatorial chemistry, high-throughput screening and gene expression profiling have been effective in the development of novel treatments for validated targets; however, a link between the downward trend in the number of new chemical entities reaching commercialization and the predominance of target-based drug discovery methods in the pharmaceutical industry has been suggested.

To address these issues, new technologies are constantly being developed and fragment-based drug design (FBDD) has emerged as a way to improve the quality and (most importantly) the efficiency of the drug discovery process. FBDD identifies the binding of low molecular weight ligands using techniques such as X-ray crystallography or NMR spectroscopy, and the binding information is then used to assemble potent lead compounds with drug-like properties.

In a recent publication, researchers at Astex Pharmaceuticals have noted that the success of FBDD often relies on the development of new synthetic methodologies for ligand elaboration. Despite the simplicity of fragment-like compounds, challenges lie in their design and synthesis as well as in developing the methodology to combine and grow fragments into high affinity leads. It is therefore important to identify compounds with attractive ‘fragment properties’ which are used as part of a selection process for adding new fragments into the Astex screening library. These include incorporation of diverse polar groups, multiple synthetically accessible positions for fragment growth in three dimensions and synthetic tractability among others.

Dihydroisoquinolone and some of its derivatives were identified in this study as ideal fragment-like compounds for the development of a FBDD-friendly synthetic methodology.

Schematic representation of synthetic elaboration of fragment 1. Growth positions are shown as blue arrows and the incorporation of aromatic heteroatoms and polar binding groups are indicated.

As proof of concept, the previously reported synthesis of dihydroisoquinolone-based compounds using Rh(III)-catalyzed C-H bond activation¹ was modified to incorporate additional potential binding groups as well as synthetic handles for efficient fragment-to-lead elaboration.

Their results illustrate an excellent example of how the application of FBDD-friendly synthetic methodology can be used to expand upon published methodologies to increase their utility in developing useful templates for fragment-based drug discovery. Although inventive ideas, such as this work, are making small contributions in pharmaceutical research, there is a need for more organic chemists to engage in these synthetic challenges if drug discovery techniques are to be fruitful in the long-run.

¹ N. Guimond et al. J. Am. Chem. Soc., 2011, 133(16), 6449–6457

To find out more see:

Design and synthesis of dihydroisoquinolones for fragment-based drug discovery (FBDD)
Nick Palmer, Torren M. Peakman, David Norton and David C. Rees
DOI: 10.1039/C5OB02461G

Victoria Corless is currently completing her Ph.D. in organic chemistry with Prof. Andrei Yudin at The University of Toronto. Her research is centred on the synthesis of kinetically amphoteric molecules, which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules.

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Revitalizing palladium-catalyzed α-arylation of enolates to generate diverse isoquinoline-based compounds

25 Jan 2016

Research efforts carried out by Professor Timothy Donohoe of Oxford University have been focussed on connecting new methodologies in organic synthesis and catalysis with impactful applications to the fields of medicinal chemistry and natural product synthesis.

One of the group’s most recent endeavors includes the development of a generalized strategy to access highly functionalized and diverse isoquinoline cores without the use of expensive and highly-specialized starting materials.

The isoquinoline motif and its derivatives are ubiquitous in a number of natural products, pharmaceutical agents, and chiral catalyst ligands. However, classical syntheses are often centered on electrophilic aromatic substitution of electron-rich systems, resulting in limited chemical diversity in accessible products. New routes are still highly desirable and a resurgence in synthetic efforts has resulted in a number of notable contributions using modern synthetic methodology.

In 2012, Prof. Donohoe and coworkers reported a sequential palladium-catalyzed α-arylation of enolates and cyclization to access isoquinolines based on chemistry originally and independently reported by Buckwald, Hartwig and Miura in 1997. Though a powerful reaction, it remained underutilized in the assembly of complex aromatic compounds. Using clever reaction engineering, Donohoe and coworkers envisioned synthesizing a psuedo-1,5-dicarbonyl accessible through α-arylation of enolizable ketones with aryl halides possessing a protected aldehyde or ketone in the ortho-position. In addition, trapping with reactive electrophiles resulted in functionalization at the C4 position. This methodology can be carried out in one pot, tolerates a wide range of substituents and most notably, provides a route to synthetically challenging electron-deficient isoquinoline scaffolds.

Palladium-catalyzed enolate arylation as a key C–C bond-forming reaction for the synthesis of isoquinolines

Their current study presents significant extensions of this earlier work and further demonstrates the innovation possible through transition metal catalysis in enabling the construction of complex architectures in interesting ways. The three- and four-component coupling procedures involve multiple bond formations in one pot from largely commercially available starting materials. Reaction versatility is demonstrated through the use of ketone, ester or nitrile enolates as well as electron-rich, electron-deficient or even sterically hindered aryl halides and in situ functionalization of intermediates to directly access a number of highly functionalized isoquinoline based compounds.

In addition to rejuvenating interesting and underexplored chemistry, Prof. Donohoe and coworkers have appreciably impacted the areas of natural product synthesis and medicinal chemistry through their innovative and streamlined synthesis of isoquinoline-based compounds and it will be interesting to see where their future endeavours will lead.

To find out more see:

Palladium-catalyzed enolate arylation as a key C–C bond-forming reaction for the synthesis of isoquinolines
Ben S. Pilgrim, Alice E. Gatland, Carlos H. A. Esteves, Charlie T. McTernan, Geraint R. Jones, Matthew R. Tatton, Panayiotis A. Procopiou and Timothy J. Donohoe
DOI: 10.1039/C5OB02320C

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Applying old tricks to new problems: Acyl Fluorides in Sterically Hindered Amide Coupling

21 Dec 2015

It comes as no surprise to those with a background in organic or medicinal chemistry that one of the most important and often-overlooked synthetic transformations is the formation of amide bonds.

Amide linkages are one of the most prolific moieties in the synthesis of pharmaceuticals and biologically active molecules. However, despite their prevalence there remain synthetic challenges, as even the simplest amides can be difficult to make.

A group at the University of Southern Denmark led by Prof. Trond Ulven has developed a protocol for amide coupling through in situ formation of acyl fluorides.

Initially, the researchers were working toward the synthesis of a molecular inhibitor for the free fatty acid receptor 2 (FFA2/GPR43), which has recently generated some interest as a target for treating various metabolic disorders.

While attempting the synthesis of an intermediate, coupling between their sterically hindered and sensitive carboxylic acid with an electron deficient and hindered amide understandably led to unsatisfactory results using standard coupling procedures.

Given the multiple steps required to generate both intermediates, the group decided to explore alternative methods to solve their problem. Indeed, acyl fluorides proved to be ideal as they behave like activated esters due to the unique nature of the carbonyl-fluoride bond while also minimizing steric hindrance between the two coupling partners.

Literature protocols are available for the generation of acyl fluorides and there are disadvantages associated with some. In recent years however, a number of alternative fluorinating agents have been reported that are capable of generating the acyl fluoride in situ under mild reaction conditions.

Prof. Ulven’s group was able to further improve the efficiency of this methodology by utilizing an alternative fluorinating agent, BTFFH, which is normally used in solid-phase peptide synthesis. This reagent reduces byproduct formation observed with reagents such as DAST, Deoxo-Fluor and XtalFluor-E. High conversions and isolated yields were obtained as a result and Ulven’s method was also successfully applied to amide coupling reactions previously reported as low yielding.

There is still a need for chemists to develop better ways to synthesize complex amide-containing structures without the need for external reagents. In the meantime, solutions such as these overcome synthetic challenges and are critical to further development and understanding in organic reaction design.

To find out more see:

A protocol for amide bond formation with electron deficient amines and sterically hindered substrates
Maria E. Due-Hansen, Sunil K. Pandey, Elisabeth Christiansen, Rikke Andersen, Steffen V. F. Hansen and Trond Ulven
DOI: 10.1039/C5OB02129D

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Dr Keith Stubbs joins Advisory Board

02 Dec 2015

We are pleased to announce that Dr Keith Stubbs, University of Western Australia, has recently joined the Organic & Biomolecular Chemistry Advisory Board.

Dr Keith Stubbs completed his undergraduate and PhD studies at UWA, followed by a two year post-doctoral position at Simon Fraser University in Vancouver, Canada. He currently is an ARC Future Fellow.

His research group mainly focusses on carbohydrate research ranging from new therapeutic targets against antibiotic and herbicide resistance to tools to study carbohydrate-processing enzymes, as well as on microfluidics as a new technique in organic synthesis.

Selection of his most recent publications:

Gaining insight into the catalysis by GH20 lacto-N-biosidase using small molecule inhibitors and structural analysis (Open Access)
Chem. Commun., 2015, 51, 15008-15011. DOI: 10.1039/C5CC05494J, Communication

An interactive database to explore herbicide physicochemical properties
Org. Biomol. Chem., 2015, 13, 5586-5590. DOI: 10.1039/C5OB00469A, Communication

A simple and robust preparation of N-acetylindoxyls: precursors for indigogenic substrates
Org. Biomol. Chem., 2015, 13, 905,-908. DOI: 10.1039/C4OB02248C, Paper

Photoredox catalysis under shear using thin film vortex microfluidics
Chem. Commun., 2015, 51, 11041-11044. DOI: 10.1039/C5CC02153G, Communication

Thin film microfluidic synthesis of fluorescent highly substituted pyridines
Green Chem., 2014, 16, 3450-3453. DOI: 10.1039/C4GC00881B, Communication

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