Organic & Biomolecular Chemistry Blog

Supplying an organism with modified precursor materials for biosynthesis is a great way of hijacking the synthetic machinery of an organism to make the compounds you want. In this paper Cormac Murphy and colleagues from University College Dublin and Ecole Normale Superieure demonstrate that precursor-directed biosynthesis is a convenient way to create analogs of rumbrin with tunable potency and selectivity, also showing that the 3-chloropyrrole moiety is not absolutely essential for biological activity in this class of polyenes. One of the compounds prepared showed dramatically improved activity against lung cancer cells.

Interested? Read this article in OBC, it is free to access for the next four weeks!

Production of anticancer polyenes through precursor-directed biosynthesis
Benjamin R. Clark, Stephen O’Connor, Deirdre Fox, Jacques Leroy and Cormac D. Murphy
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C1OB05667K

Brucella spp. are the causative organisms for the zoonotic disease Brucellosis, which in humans may require months of treatment and can kill. As there is no human vaccine, new treatments are needed.

Stephan Köhler and Jean-Yves Winum from CNRS, and their colleagues, have created a new series of inhibitors that are highly active in vitro, and are shown to be active in vivo. Additionally, molecular modelling and competition experiment with NAD+ confirmed the positioning of the inhibitor inside the active site of HDH. As the target HDH has been directly linked to bacterial virulence, and with the results obtained on live extra- and intracellular brucellae, the development of these inhibitors can be considered as a promising step towards novel anti-virulence drugs.

The referees thought this article was very significant, and so do we – so read this HOT article today in OBC. It is free to download until 5th May.

Anti-virulence Strategy against Brucella suis: Synthesis, Biological Evaluation and Molecular Modeling of Selective Histidinol Dehydrogenase Inhibitors
Marie-Rose Abdo, Pascale Joseph, Jérémie Mortier, François Turtaut, Jean-Louis Montero, Bernard Masereel, Stephan Köhler and Jean-Yves Winum
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C1OB05149K

Cellular oxidative stress is thought to lie behind many disease and ageing processes, so an understanding of its effects is vital to designing strategies to counter such damage. Cynthia J. Burrows et al. from University of Utah have conducted a characterisation study of the nucleoside degradation products of copper-mediated Fenton reactions and determined the major product to be a recently discovered hydantoin, d2Ih. The products contrast with those produced in radiation-induced oxidation and the discovery of a new product, dGh_red, in the double-stranded oligodeoxynucleotide studies points the way for future chemical and biological studies in this vital area.

The referees thought this was a very significant work so read this HOT article today in OBC – it is free to access until 28th April!

Characterization of 2′-deoxyguanosine oxidation products observed in the Fenton-like system Cu(II)/H2O2/reductant in nucleoside and oligodeoxynucleotide contexts
Aaron M. Fleming, James G. Muller, Insun Ji and Cynthia J. Burrows
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C1OB05112A

Terpenes and other polycycles are very common in nature and as many are biologically active, have been a key target for synthetic organic chemists. Rama Heng and Samir Zard from Ecole Polytechnique in France have demonstrated a general approach to polycyclic structures featuring the direct formation of six-, seven-, and eight-membered rings. This very powerful, yet concise and highly flexible, approach to both fused and bridged polycyclic structures overcomes the limitations imposed by intrinsically slow radical transformations, opening numerous synthetic opportunities. Our referees were very enthusiastic about this paper and we think you will be too – expect to see more about this exciting new method!

This HOT article is available free until 21st April 2011! Read it today in OBC.

A flexible, unified radical-based approach to polycyclic structures
Rama Heng and Samir Z. Zard
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB00024A

Ever wanted to carry some polyions across a cell membrane? Some DNA perhaps? Well it turns out you could do with the help of a molecular octopus!

Stefan Matile et al. from the University of Geneva have undertaken a comprehensive study into the structural factors affecting the ability of “octopus” amphiphiles to carry polyions across lipid bilayers and found that the number of “tentacles” was a key factor. Their work has highlighted three key results: firstly, their approach to structure development allowed rapid production and screening of counterion libraries; secondly they have shown that activity related to tail length is also dependent on the number of tails; and finally they found that branched tails were better than their linear analogs.

These findings have a broad application across the fields of sensing, catalysis, cellular uptake and anything else that relies on transporting polyions across a membrane.

Read this HOT article now in Org. Biomol. Chem. – it is available free until 14/04/2011.

Comprehensive screening of octopus amphiphiles as DNA activators in lipid bilayers: implications on transport, sensing and cellular uptake
Javier Montenegro, Andrea Fin and Stefan Matile
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C0OB00948B

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

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

T. cruzi, the causative agent of Chagas disease, relies on its enzyme trans-sialidase for part of its infectivity. Robert Field et al., from several collaborating institutions worldwide, have studied this enzyme, highlighting the wide range of structures and functionalities that it can accommodate. This study has demonstrated important features for potential inhibitor design (a therapeutic target for Chagas’ disease) and also opens up possibilities for using the versatility of this enzyme more generally as a catalyst for α-(2→3)-sialylglycoconjugate synthesis.

This HOT article is now free to access until 22nd February.

Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries
Jennifer A. Harrison, K. P. Ravindranathan Kartha, Eric J. L. Fournier, Todd L. Lowary, Carles Malet, Ulf J. Nilsson, Ole Hindsgaul, Sergio Schenkman, James H. Naismith and Robert A. Field
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00826E, Paper

When a referee calls a paper outstanding you know you are onto a good thing!
Pirali et al. from Università degli Studi del Piemonte Orientale “A. Avogadro” have documented a straightforward synthesis of dialkyl 2-acyl-5-aminofuran-3,4-dicarboxylates, displaying four points of diversity and an unprecedented substitution pattern. The products are easily isolated and the functional groups are ripe for further derivatisation, making this a reaction which is both mechanistically interesting and also has practical value for synthetic and medicinal chemists.

Both reviewers thought this HOT article would be of wide interest in the organic community and it is now free to access until 18th February.

Read it today in OBC.

A novel α-isocyanoacetamide-based three-component reaction for the synthesis of dialkyl 2-acyl-5-aminofuran-3,4-dicarboxylates
Riccardo Mossetti, Diego Caprioglio, Giampiero Colombano, Gian Cesare Tron and Tracey Pirali
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00979B

Adrien Quintard and Alexandre Alexakis from the University of Geneva report a systematic study on the application and scope of the 1,2-sulfone rearrangement and notably on its asymmetric variant. 

A wide variety of nucleophiles can be used to yield highly functionalised substrates, with some demonstrating excellent enantioselectivities of up to 94% ee.  This 1,2-sulfone rearrangement constitutes an alternative to the use of expensive 1,1-bis(phenylsulfonyl)ethene and leads to a formal alkylation of the nucleophile.

Both reviewers thought this HOT article would be of very wide interest in the organic community and it is now free to access until 8th February.

1,2-Sulfone rearrangement in organocatalytic reactions
Adrien Quintard and Alexandre Alexakis
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00818D