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

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

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