Diversification of a Multicomponent Reaction

Arun Ankush Tanpure, a graduate student at IISER Pune, India, writes on a recent OBC article

The Ugi reaction was one of the very first multicomponent reactions exploited to develop chemical libraries, which further extended to combinatorial, solid phase and flow synthesis for evolving new lead structures of active agents. Implementing the Ugi reaction in combination with other organic reactions enlarges the chemical diversity of possible products.

Researchers at Vrije University Brussel, led by Steven Ballet, have made a step forward by executing a one-pot Ugi-Huisgen tandem reaction and found an alternative high atom economy pathway for the synthesis of conformationally constrained, amino-triazoloazepinone-containing di- and tripeptides.

Strategically, they have used an unconventional azide containing acid, and alkyne amine along with traditional aldehydes and isocyanides. By using equimolar reactants with very mild reaction conditions, they were able to observe total conversion to the linear Ugi-compounds equipped with azide and alkyne functionality. Furthermore, they have cyclised the resulting compounds into the respective triazoles, by performing a catalyst-free Huisgen cycloaddition reaction in a sealed tube.

Variation in substitution patterns and tolerance of a large array of aldehydes in this methodology will open a new avenue for the synthesis of various building blocks to be used in peptidomimetics with a wide range of applications.

Find out more in their Communication:

Efficient synthesis of conformationally constrained, amino-triazoloazepinone-containing di- and tripeptides via a one-pot Ugi–Huisgen tandem reaction
T. M. A. Barlow, M. Jida, D. Tourwéa and S. Ballet
DOI: 10.1039/C4OB01381F

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Q2 Top Ten most accessed articles

The 10 most accessed Organic & Biomolecualr Chemistry articles between April and June 2014 – Free to access until the end of October

During the months April – June 2014, the most downloaded Organic & Biomolecualr Chemistry articles were:

Design, synthesis, and application of tartaric acid derived N-spiro quaternary ammonium salts as chiral phase-transfer catalysts
Mario Waser, Katharina Gratzer, Richard Herchl and Norbert Müller
DOI: 10.1039/C1OB06573D

Far-red and near infrared BODIPY dyes: synthesis and applications for fluorescent pH probes and bio-imaging
Yong Ni and Jishan Wu
DOI: 10.1039/C3OB42554A

Direct acylation of N-benzyltriflamides from the alcohol oxidation level via palladium-catalyzed C–H bond activation
Jihye Park, Aejin Kim, Satyasheel Sharma, Minyoung Kim, Eonjeong Park, Yukyoung Jeon, Youngil Lee, Jong Hwan Kwak, Young Hoon Jung and In Su Kim
DOI: 10.1039/C3OB40140E

sp3 C–H oxidation by remote H-radical shift with oxygen- and nitrogen-radicals: a recent update
Shunsuke Chiba and Hui Chen
DOI: 10.1039/C4OB00469H

Watsonianone A–C, anti-plasmodial β-triketones from the Australian tree, Corymbia watsoniana
Anthony R. Carroll, Vicky M. Avery, Sandra Duffy, Paul I. Forster and Gordon P. Guymer
DOI: 10.1039/C2OB26931G

Recent advances in biocompatible nanocarriers for delivery of chemotherapeutic cargoes towards cancer therapy
Chung Yen Ang, Si Yu Tan and Yanli Zhao
DOI: 10.1039/C4OB00164H

Continuous flow chemistry: a discovery tool for new chemical reactivity patterns
Jan Hartwig, Jan B. Metternich, Nikzad Nikbin, Andreas Kirschning and Steven V. Ley
DOI: 10.1039/C4OB00662C

Bifunctional primary amine-thioureas in asymmetric organocatalysis
Olga V. Serdyuk, Christina M. Heckel and Svetlana B. Tsogoeva
DOI: 10.1039/C3OB41403E

Palladium-catalyzed three-component reaction of N-tosylhydrazone, norbornene and aryl halide
Fangdong Hu, Ying Xia, Zhenxing Liu, Chen Ma, Yan Zhang and Jianbo Wang
DOI: 10.1039/C4OB00590B

A coumarin-quinolinium-based fluorescent probe for ratiometric sensing of sulfite in living cells
Li Tan, Weiying Lin, Sasa Zhu, Lin Yuan and Kaibo Zheng
DOI: 10.1039/C4OB00132J

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Winners at the 25th Symposium on Physical Organic Chemistry

From left to right: Professor Yoshito Tobe (President) Mr. Tomoya Nakamura (OBC) Mr. Yuta Shiina (RSC Advances) Mr. Hirotaka Mori (Chemical Science) Hiroyuki Isobe (Organizer)

Congratulations to the winners of the poster prizes at the 25th Symposium on Physical Organic Chemistry (Japan), which was held September 7th to September 9th in Sendai.

Organic & Biomolecular Chemistry prize: Mr. Tomoya Nakamura (Supervisor: Professor Eiichi Nakamura), Department of Chemistry, The University of Tokyo
Title: Benzodipyrrole-Based Donor-Acceptor Type Boron Complexes for Near-Infrared Absorption

RSC Advances prize: Mr. Yuta Shiina (Supervisor: Professor Nagao Kobayashi), Department of Chemistry, Tohoku University
Title: Redox-control of Molecular Alignment of TTF-Annulated Silicon Phthalocyanine Oligomers

Chemical Science prize: Mr. Hirotaka Mori (Supervisor: Professor Atsuhiro Osuka), Department of Chemistry, Kyoto University
Title: Synthesis and Properties of 5,20-α-Oligothienyl-substitued [26]Hexaphyrins

The event organised by the Society of Physical Organic Chemistry, Japan,  saw 624 participants attend, with 2 keynote lectures from E. Nakamura & C. Nuckolls.  In addition there were 328 poster presentations, and 96 oral presentations.

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HOT Organic & Biomolecular Chemistry articles

Check out the following HOT articles, as recommened by the reviewers of the articles. These have all been made free to access until 20th October:

Estimating the shape and size of supramolecular assemblies by variable temperature diffusion ordered spectroscopy
Benjamin M. Schulze, Davita L. Watkins, Jing Zhang, Ion Ghiviriga and Ronald K. Castellano
DOI: 10.1039/C4OB01373E, Communication


Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification
James J. Sahn, Brett A. Granger and Stephen F. Martin
DOI: 10.1039/C4OB00835A, Review Article
From themed collection In Celebration of Richard Taylor’s 65th Birthday


Development and mechanistic studies of an optimized receptor for trimethyllysine using iterative redesign by dynamic combinatorial chemistry
Nicholas K. Pinkin and Marcey L. Waters
DOI: 10.1039/C4OB01249F, Paper


Modulation of DNA–polyamide interaction by β-alanine substitutions: a study of positional effects on binding affinity, kinetics and thermodynamics
Shuo Wang, Karl Aston, Kevin J. Koeller, G. Davis Harris, Nigam P. Rath, James K. Bashkin and W. David Wilson
DOI: 10.1039/C4OB01456A, Paper


Iridium-catalyzed C–H borylation of pyridines
Scott A. Sadler, Hazmi Tajuddin, Ibraheem A. I. Mkhalid, Andrei S. Batsanov, David Albesa-Jove, Man Sing Cheung, Aoife C. Maxwell, Lena Shukla, Bryan Roberts, David C. Blakemore, Zhenyang Lin, Todd B. Marder and Patrick G. Steel
DOI: 10.1039/C4OB01565G, Paper


Efficient synthesis of conformationally constrained, amino-triazoloazepinone-containing di- and tripeptides via a one-pot Ugi–Huisgen tandem reaction
T. M. A. Barlow, M. Jida, D. Tourwé and S. Ballet
DOI: 10.1039/C4OB01381F, Communication


Influence of B-ring modifications on proton affinity, transmembrane anion transport and anti-cancer properties of synthetic prodigiosenes
Estelle Marchal, Soumya Rastogi, Alison Thompson and Jeffery T. Davis
DOI: 10.1039/C4OB01399A, Paper


Catalytic amide allylation of α-ketoesters: extremely high enantioselective synthesis of ester functionalised α-methylene-γ-butyrolactones
Masaki Takahashi, Yusuke Murata, Masahiro Ishida, Fumitoshi Yagishita, Masami Sakamoto, Tetsuya Sengoku and Hidemi Yoda
DOI: 10.1039/C4OB01508H, Communication


Recent developments in transition metal-catalysed spiroketalisation
Rachelle Quach, Daniel F. Chorley and Margaret A. Brimble
DOI: 10.1039/C4OB01325E, Perspective


Non-isoprenoid polyene natural products – structures and synthetic strategies
Katrina S. Madden, Fathia A. Mosa and Andrew Whiting
DOI: 10.1039/C4OB01337A, Review Article


A Lewis acid-mediated conformational switch
Peter C. Knipe, Hannah Lingard, Ian M. Jones, Sam Thompson and Andrew D. Hamilton
DOI: 10.1039/C4OB01556H, Paper

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RSC Organic Division Poster Symposium 2014 one month left to submit

Calling all final year organic chemistry PhD students

There is only one month left to submit your abstract for the RSC Organic Division’s poster symposium, headline sponsored by F. Hoffmann-La Roche, Ltd.

When & where?

The symposium will take place at The Royal Society of Chemistry, Burlington House, London on Monday 01 December 2014 and offers you the chance to showcase your research to your peers, leading academics and industrial chemists.

Prizes

There will be a first prize of £500, two runner-up prizes of £250, and a “selected by Industry Prize” also 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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Myriad Multiplicity in Nitroenamine Multicomponent Methodology

Posted on behalf of Jennifer Lee, guest web writer for Organic & Biomolecular Chemistry

Not many molecules can claim to be both a Michael donor and Michael acceptor while containing a good leaving group as is the case with nitroketene-N,S-acetals like N-methyl-S-methyl nitroethylene (NMSM), broadly categorized as nitroenamines.

As a double actor in the pseudo three-component reaction investigated by Rao and Parthiban, moieties of NMSM react three times in two roles:  twice as a nucleophile and once as an electrophile.  The other components in the same pot included the aromatic aldehyde and catalytic 2-aminopyridine.

The methodology generates an alternate route from the classic Hantzsch reaction to the 1,4-dihydropyridine (DHP) platform with a broader scope and purification by recrystallization.  Advantageously, 1,4-DHPs are calcium channel blockers and hydride sources for reduction.

The functionally-rich NMSM component conveniently diversifies DHP which could lead to more potent medicinal applications or pesticides.

The two inherent diversity points on the platform arose from the aldehyde and amine precursors.  Additional diversity from amine substitution of the built-in sulfide leaving group created a total of 29 unique 1,4-DHP possibilities.

Specifically, they synthesized a neonictinoid insecticide analogue to the popular nitenpyram compound to constrain the alkene to the cis-isomer with muted toxicity to mammals.

Overall, leveraging an electronically versatile synthon like NMSM in a multicomponent reaction leads to enhanced diversity for analoging with myriad compounds that could perform better than those currently available.

To find out more see:

One-pot pseudo three-component reaction of nitroketene-N,S-acetals and aldehydes for synthesis of highly functionalized hexa-substituted 1,4-dihydropyridines
H. Surya Prakash Rao and A. Parthiban
DOI: 10.1039/c4ob00628c

Jennifer LeeJennifer Lee is currently a Ph.D. candidate in Dr. George Kraus’ organic chemistry lab at Iowa State University.  Her research focuses on designing methodologies to transform carbohydrate-derived biomass into biorenewable commodity and specialty chemicals.  The creation of a versatile platform technology led to diverse and industrially-relevant aromatic compounds to work toward a more sustainable future.

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Vaccines for heroin

Arun Ankush Tanpure, a graduate student at IISER Pune, India, writes on a recent OBC article

The number of deaths due to heroin overdoses has severely increased in last decade, and regular consumption of heroin leads to serious health concerns.

Vaccination is one of the emerging choices among heroin rehabilitation therapies. In general, these vaccines contain heroin-like hapten as a pharmacophore that acts as an antagonist. This antagonist has high affinity for heroin receptors but does not activate them, hence reverses the effects of heroin. Because of inherent chemical instability, when entered in to bloodstream these anti-heroin drugs rapidly metabolise into several by-products, which makes development of effective vaccines against heroin particularly challenging.

Recently an American research group at National Institute on Drug Abuse (NIDA) lead by Professor Kenner Rice has reported the synthesis and immunological evaluation for a series of haptens.

The team has emphasised the hydrolytic stability of hapten scaffolds and envisioned that hapten with amido groups at both the C3 and C6 positions should be more stable than a hapten with an ester in one of those positions. Insertion of a 3-amino group and the construction of a C-6α-(2-oxo-propyl) group stereoselectively was the challenging task towards the synthesis of designed hapten derivatives. The group has tackled the synthetic hurdle by adopting convergent synthesis approach and validating the stereochemistry by single X ray crystallography.

Furthermore, in vivo Immunological studies of all three new synthetic haptens reveals that one derivative DiAmHap (3) is chemically more stable and better candidate for a heroin vaccine than 6-PrOxyHap (1) and DiPrOxyHap (2). This work is a very positive step towards the development of vaccines for heroin abuse.

Synthesis and immunological effects of heroin vaccines
Fuying Li, Kejun Cheng,  Joshua F. G. Antoline, Malliga R. Iyer, Gary R. Matyas, Oscar B. Torres, Rashmi Jalah, Zoltan Beck, Carl R. Alving, Damon A. Parrish, Jeffrey R. Deschamps, Arthur E. Jacobson and Kenner C. Rice
DOI: 10.1039/C4OB01053A

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Amino acids: fluorescensors for mercury ions

Arun Ankush Tanpure, a graduate student at IISER Pune, India, writes on a recent OBC article

Many human activities have been responsible for heavy metal poisoning in recent years, Mercury (Hg) poisoning being one of them. Mercury occurs in several forms and even trace concentrations of mercury ions in crops, fish or the human body are enough to produce potentially toxic effects to vital organs. Mercury poisoning can lead to several diseases including Acrodynia (also known as the pink disease), the Hunter-Russell syndrome and the Minamata disease.

Selective detection of mercury, particularly in aqueous media, has been a key area for analytical chemists, since traditional analytical techniques for mercury detection are time consuming, laborious and involve expensive instrumentation. In this work, Korean researcher Keun-Hyeung Lee and co-workers have developed a pair of very sensitive amino acid based fluorescence-ON probes for the exclusive detection of mercury ions in aqueous solution.

The team has combined the fluorescence properties of pyrene and Hg(II) binding ability of tyrosine residues for the design and synthesis of two novel fluorescensors. Both newly-synthesised probes show emission maxima at 386 and 400 nm in the absence of Hg(II) ion. Upon titration with Hg(II) ions, both probes show exponential fluorescence enhancement and display a remarkable red shift (90-100 nm) emission. These probes are also highly selective for mercury ions in the presence of a range of other metal ions and are effective in aqueous solutions.

The team further clarifies the binding mode of these sensors and the coordination of the metal ion. This method can be implemented for rapid and quantitative detection of Hg(II) from various polluted water sources. This work also underscores the unconventional use of an amino acid as a chemosensor.

Ratiometric fluorescence chemosensor based on tyrosine derivatives for monitoring mercury ions in aqueous solutions
Ponnaboina Thirupathi, Ponnaboina Saritha (née Gudellin) and Keun-Hyeung Lee
DOI: 10.1039/C4OB01044B

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Recent HOT Organic & Biomolecular Chemistry articles

Check out the following HOT articles, these have been made free to access for a limited time:

Synthesis and immunological effects of heroin vaccines
Fuying Li, Kejun Cheng, Joshua F. G. Antoline, Malliga R. Iyer, Gary R. Matyas, Oscar B. Torres, Rashmi Jalah, Zoltan Beck, Carl R. Alving, Damon A. Parrish, Jeffrey R. Deschamps, Arthur E. Jacobson and Kenner C. Rice
Org. Biomol. Chem., 2014, Advance Article
DOI: 10.1039/C4OB01053A

Synthesis and immunological effects of heroin vaccines

Free to access until 21st August 2014


6-Azido hyacinthacine A2 gives a straightforward access to the first multivalent pyrrolizidine architectures
Giampiero D’Adamio, Camilla Parmeggiani, Andrea Goti, Antonio J. Moreno-Vargas, Elena Moreno-Clavijo, Inmaculada Robina and Francesca Cardona
Org. Biomol. Chem., 2014,12, 6250-6266
DOI: 10.1039/C4OB01117A

6-Azido hyacinthacine A2 gives a straightforward access to the first multivalent pyrrolizidine architectures

Free to access until 21st August 2014


Relative contractile motion of the rings in a switchable palindromic [3]rotaxane in aqueous solution driven by radical-pairing interactions
Leah S. Witus, Karel J. Hartlieb, Yuping Wang, Aleksandrs Prokofjevs, Marco Frasconi, Jonathan C. Barnes, Edward J. Dale, Albert C. Fahrenbach and J. Fraser Stoddart
Org. Biomol. Chem., 2014,12, 6089-6093
DOI: 10.1039/C4OB01228C

Relative contractile motion of the rings in a switchable palindromic [3]rotaxane in aqueous solution driven by radical-pairing interactions

Free to access until 21st August 2014


Catalytic control over the formation of supramolecular materials
Rienk Eelkema and Jan H. van Esch
Org. Biomol. Chem., 2014, Advance Article
DOI: 10.1039/C4OB01108B

Catalytic control over the formation of supramolecular materials

Free to access until 21st August 2014


Comparison of the substrate selectivity and biochemical properties of human and bacterial γ-butyrobetaine hydroxylase
Anna M. Rydzik, Ivanhoe K. H. Leung, Grazyna T. Kochan, Nikita D. Loik, Luc Henry, Michael A. McDonough, Timothy D. W. Claridge and Christopher J. Schofield
Org. Biomol. Chem., 2014, Advance Article
DOI: 10.1039/C4OB01167H

Comparison of the substrate selectivity and biochemical properties of human and bacterial γ-butyrobetaine hydroxylase

Free to access until 21st August 2014


Diaporine, a novel endophyte-derived regulator of macrophage differentiation
Hao Chen Wu, Hui Ming Ge, Le Yun Zang, Yun Cheng Bei, Zhi Yuan Niu, Wei Wei, Xiu Jing Feng, Sen Ding, Seik Weng Ng, Ping Ping Shen and Ren Xiang Tan
Org. Biomol. Chem., 2014, Advance Article
DOI: 10.1039/C4OB01123F

Diaporine, a novel endophyte-derived regulator of macrophage differentiation

Free to access until 21st August 2014


New reagents for detecting free radicals and oxidative stress
Mina Barzegar Amiri Olia, Carl H. Schiesser and Michelle K. Taylor
Org. Biomol. Chem., 2014, Advance Article
DOI: 10.1039/C4OB01172D

New reagents for detecting free radicals and oxidative stress

Free to access until 21st August 2014

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14th Anglo-Italian Meeting on Heterocyclic Chemistry

The 14th Anglo-Italian Meeting on Heterocyclic Chemistry, organised by the Heterocyclic & Synthesis Group in collaboration with the Italian Chemical Society, recently took place.

14th Anglo-Italian Meeting on Heterocyclic Chemistry conference photo 2014

It was an excellent meeting, held at Cumberland Lodge in Windsor Great Park, with around 50 participants, equally split between the two countries. There were some excellent lectures, including plenaries from:

  • Professor Stephen Clark (University of Glasgow)
  • Professor Sabine Flitsch (University of Manchester)
  • Dr King Kuok (Mimi) Hii (Imperial College London)
  • Professor Emanuela Licandro (University of Milan)
  • Professor Andrea Pace (University of Palermo)
  • Professor Claudio Trombini (University of Bologna)

Our congratulations go to  Susan Lepri from University of Perugia who won our poster prize.

Susan receiving her prize from Professor Chris Willis (Heterocyclic Group) and Professor Giuseppe Musumarra (Italian Chemical Society)

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