Organic & Biomolecular Chemistry Blog

When facing the synthesis of highly electron deficient monoaryl, di-aryl and bis-diaryl acetonitriles, Christopher Gorman and his research group at North Carolina State University look at two different methods: Nucleophilic aromatic substitution (NAS) and palladium-mediated coupling.

In their search for the most efficient method, they show that palladium-mediated coupling is more efficient than nucleophilic aromatic substitution for cyano-containing, electron deficient molecules. They further show that choice of solvent, base and supporting ligand has a large effect on the yield of this coupling.

Read all of this in this HOT article that is free to access until the 31st March.

Overcoming challenges in the palladium-catalyzed synthesis of electron deficient ortho-substituted aryl acetonitriles
Molly C. Brannock, William J. Behof, Gregory Morrison and Christopher B. Gorman
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB00903B

Drug design and discovery in a research lab is already a very challenging task. It involves knowledge, intensive research, resources, a bit of luck and a lot of time. However, eureka moments do happen and when they happen it feels great.

However, the story does not finish there. One thing is the synthesis of a new drug in a lab (mg scale) but being able to scale that up to the multigram (or kilogram if you are lucky) scale in a non-expensive and safe manner that can be implemented in industry, well… THAT is the biggest challenge!

In this paper, Xiaohu Deng and colleagues at Johnson & Johnson Pharmaceutical Research and Development in San Diego, describe the ‘ideal synthesis’ of a CCK1/CCK2 dual receptor antagonist on a multi-gram scale, without protecting groups and in an environmentally friendly way.

This is an example of how academic research is translated into industrial applications.

Both the referees and the editorial office found this paper very interesting and selected it as a HOT article, which means it is free to access for 4 weeks! Download it now.

Protecting-group-free synthesis of a dual CCK1/CCK2 receptor antagonist
Jing Liu, Xiaohu Deng, Anne E. Fitzgerald, Zachary S. Sales, Hariharan Venkatesan and Neelakandha S. Mani
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01004A, Paper

Aminoglycoside antibiotics are widely used in hospitals to treat serious and life-threatening infections. Because of their widespread use, bacterial resistance is becoming more of a problem and the search for aminoglycosides which are not affected grows ever more urgent.

Sylvie Garneau-Tsodikova, Micha Fridman and their colleagues from University of Michigan and Tel Aviv University have investigated the effect of 6′- and 6′′′-N-acylation of aminoglycosides on their ability to avoid bacterial resistance while retaining their antibiotic effect. The best compounds synthesised retained their full antibiotic effect against resistant strains whilst that of their parent compound was compromised. The authors have thus opened up a new route for aminoglycoside modification and demonstrated effective lead compounds for further development—the evolutionary struggle between man and pathogenic bacteria continues.

The referees enjoyed this paper and so did we, so read this HOT article in OBC today! It is free to access until 1st April 2011.

Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance
Pazit Shaul, Keith D. Green, Roi Rutenberg, Maria Kramer, Yifat Berkov-Zrihen, Elinor Breiner-Goldstein, Sylvie Garneau-Tsodikova and Micha Fridman
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C0OB01133A, Paper

Molecular self-assembly is an area of research that has spectacularly grown during the last two decades. The design of macromolecules that can adopt specific shapes and can act as receptors or host other molecules through non-covalent interactions has attracted particular attention.

One of the most popular building blocks in self assembly is calixarenes.  However, although calix-[4]-arenes have been widely studied in the field of molecular recognition, calix-[6]-arenes have not received as much attention due to the flexibility of their skeleton. The design of calix-[6]-arenes is still a challenging task.

In this paper, Stephane Le Gac, Ivan Jabin and co-workers take advantage of the versatility of the calix[6]arene functionalization together with the flexibility of its skeleton to create additional host-guest and host-host interactions. The resulting supramolecular receptors are unique since these additional interactions are reminiscent of intra-protein interactions in biological receptors.

If you want to find out more about these unique supramolecular receptors, download this HOT paper which is free to access until 23rd March.

Allosterically driven self-assemblies of interlocked calix[6]arene receptors
Stéphane Le Gac, Jean-François Picron, Olivia Reinaud and Ivan Jabin
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB01020K

Paul-Alain Jaffrès et al. from the Université de Brest report the synthesis of cationic lipo-phosphoramidates and lipo-thiophosphoramidates possessing the capacity to compact and transfect plasmid DNA. They investigated the effect of different functional groups on the physico-chemical properties of the lipids and found that they could fine tune the fluidity and fusogenicity of the liposomes. The best of the thiophosphoramidates synthesised provided highly efficient transfection—even at low charge levels, in contrast to the older phosphoramidates—demonstrating that a minor modification of the chemical structure of the cationic lipids may have a direct impact on their gene transfection ability.

As all our HOT articles, this is free to access for 4 weeks (until 23rd March).

Cationic lipo-thiophosphoramidates for gene delivery: synthesis, physico-chemical characterization and gene transfection activity – comparison with lipo-phosphoramidates
Aurore Fraix, Tristan Montier, Nathalie Carmoy, Damien Loizeau, Laure Burel-Deschamps, Tony Le Gall, Philippe Giamarchi, Hélène Couthon-Gourvès, Jean-Pierre Haelters, Pierre Lehn and Paul-Alain Jaffrès
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00981D