Anti-Anthrax Agents Means That New Antibiotics Are Needed to the 14-Membered Ring

research highlights

NATURAL PRODUCTS infection and its resistance to treatment system — along with a dichloro group on Anti-anthrax agents means that new antibiotics are needed to the 14-membered ring. Fenical and the Angew. Chem. Int. Ed. 52, 7822–7824 (2013) target this bacterium. team decided to incorporate this dichloro In an effort to discover new antimicrobial moiety into anthracimycin to see what H H scaffolds, a team led by William Fenical at the effect this would have on the antimicrobial University of California at San Diego, USA, activity. Interestingly, the dichloro analogue H H H isolated metabolites from a marine organism was approximately half as potent against H H Cl H (a species of Streptomyces) and tested them Bacillus anthracis, however, it exhibited O O O O Cl for antibacterial activity. One metabolite greater activity against some strains of O O H O O showed potent activity against the Gram- Gram-negative bacteria — which the team positive Bacillus anthracis and methicillin- believe is linked to easier penetration Anthracimycin Dichloro analogue resistant Staphylococcus aureus; although through the cell wall. RJ it had only very limited activity against Few diseases carry the sinister connotations Gram-negative bacteria such as Escherichia REACTIVE INTERMEDIATES of anthrax. It is a deadly infection that coli. A series of NMR spectroscopy, mass Non-classical crystals predominantly affects herbivores, although spectrometry and X-ray crystallography Science 341, 62–64 (2013) it has also been used for bioterrorism analyses enabled the team to characterize and adapted for biowarfare. Anthrax is the structure and stereochemistry of this When either enantiomer of exo-2-norbornyl caused by Bacillus anthracis, and, like other new antimicrobial compound — which they bromide reacts with a nucleophile, a racemic bacterial diseases, it is normally treated with termed anthracimycin. The compound has mixture of products results. Explaining the antibiotics; however, because the infection an unusual triple-ring system formed from stereochemical outcome of this reaction does not always respond to treatment — and 14, 6 and 6 atoms, respectively, as well as an has been at the heart of a long-running because the infection needs to be completely enolized β-diketone. debate about the structure of the cationic eradicated — the course of antibiotics may Although the tricyclic ring system reaction intermediate — and whether it is a need to be taken for up to six months, or found in anthracimycin is rare, it is not so-called non-classical carbocation. Now, in as a continuous intravenous supply. This unprecedented. A related metabolite called what seems to be the final (and definitive) dangerous combination of a potentially lethal chlorotonil features the same tricyclic ring argument in this famous case, a team of

TRANSITION METAL COMPLEXES

24-carat chemistry Angew. Chem. Int. Ed. http://dx.doi.org/10.1002/anie.201304820 (2013)

From the City of Gold to the Golden Fleece, from the Californian gold rush to the earliest ‘al’chemists, gold has captured our imagination like few other

elements have. Unlike most elements, 1 gold is typically found in nature in its pure 1 $X $X $X elemental form. In complexes, its common 1 oxidation states are −i, +i and +iii, with the 1 odd rare compound featuring gold +ii, +iv and +v. Apart from the elemental form, however, the zero oxidation state of gold

has generally remained elusive to chemists. © 2013 WILEY There have been some examples of mixed gold(i)/gold(0) complexes and mixed- two cyclic (alkyl)(amino)carbene (CAAC) Phosphines are currently used as metal clusters where an oxidation state ligands, forming a linear L–Au–L structure in ligands to stabilize gold clusters of various of zero was assigned to gold. But simple the case of the mononuclear complex and sizes, and these have found a wide range

mononuclear (LnAu), binuclear (LAu- slightly bent L–Au–Au L dinuclear compound. of applications as organic photovoltaics AuL) and polynuclear [(LAu)n] neutral CAACs are good π-electron acceptors, which and therapeutic agents and in catalysis. complexes, with atoms of gold coordinated helps them to stabilize the electron-rich However, gold particles stabilized by end-on by ligands, have not been isolated. gold(0) centres; the carbene ligands are phosphines have all been positively charged. A team from the USA and Germany, capable of forming strong bonds with the Thus, the ability of these CAAC ligands to led by Guy Bertrand at the University of gold atoms. The green (mononuclear) and stabilize gold in the formal zero oxidation California, San Diego, have now managed brown (dinuclear) complexes are stable for state could open the door to the synthesis of to isolate metal–ligand complexes — days at room temperature in solution and neutral, differently sized gold clusters. These containing either one or two gold atoms in the solid state, and the team were able to tiny ‘nuggets’ of neutral gold could provide — in which the formal oxidation state of the determine their structures (pictured) using a wealth of future opportunities in catalysis metal atoms is zero. Each complex features X-ray crystallography. and other applications. RD

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