Chemical Science Blog

The promising anticancer compound nutlin-3 is likely to become more widely available to researchers thanks to a new synthetic protocol developed by US chemists.

Nutlins, a group of compounds centred on a nitrogen-containing heterocycle, were discovered by scientists working for Hoffman-La Roche in 2004 and were found to inhibit a key interaction between two proteins involved in cancer pathways, with nutlin-3 the most potent of these.

The compound has attracted widespread interest but details of its synthesis are difficult to glean from the available literature – no full protocol has been published. The molecule has multiple chiral centres and synthesising the required stereoisomer is difficult.

Tyler Davis and Jeffrey Johnston at Vanderbilt University in Tennessee have used catalysts they developed to devise a straightforward synthesis of nutlin-3 that is highly selective for the required stereoisomer.

To find out more, read the full news story in Chemistry World and download Johnston’s Chemical Science article for free.

A rare example of hydroxyl-directed C-H functionalisation has been reported by US chemists, demonstrating how molecular complexity can be drastically advanced in a single step.

Jin-Quan Yu and colleagues at the Scripps Research Institute, La Jolla, synthesised a series of 1-isochromanones – key structural motifs in natural products and drug candidates – using palladium-catalysed C-H carbonylation. The team found that amino acid ligands could promote the reaction, which is the first example of ligand-enabled C–H carbonylation.

The protocol represents a rare case in which the directing group (which typically needs to be removed after C-H functionalisation) and the coupling partner are fully incorporated into the target molecule without further synthetic manipulations. It is an encouraging step forward to improving atom- and step-economy in organic synthesis, says Yu.

Read Yu’s Edge article in Chemical Science to find out more.

Also of interest:
Professor Yu is guest editor of a recently published Chem Soc Rev themed issue on C-H functionalisation in organic synthesis. Read the issue today to stay abreast of this burgeoning field.

A century on from the discovery of superconductivity there is still a huge worldwide effort to understand the mechanism of this intriguing phenomenon and find new superconductors. Scientists recently discovered superconductivity in alkali metal iron selenium systems and explaining this observation is now of great interest.

UK researchers have taken a step in the right direction by reporting precise structural information for this family of superconductive materials. By understanding how vacancies in these structures’ compositions can be accommodated, the team hopes to have laid the foundation for all subsequent understanding of the origin of superconductivity in related systems.

To find out more, read the Edge article for free in Chemical Science:

Cation vacancy order in the K_0.8+xFe_1.6-ySe₂ system: five-fold cell expansion accommodates 20% tetrahedral vacancies
J. Bacsa, A.Y. Ganin, Y. Takabayashi, K.E. Christensen, K. Prassides, M.J. Rosseinsky, J.B. Claridge, Chem. Sci., 2011, DOI: 10.1039/C1sc00070E

Matthew Rosseinsky is a Chemical Science Associate Editor handling work in the area of inorganic materials. Submit to his editorial office today.

Technology that could bring flow chemistry into the domain of complex natural product synthesis has been developed by UK scientists. 

The best things in life don’t come without a struggle – or so the saying goes. It certainly appears that way with chemistry. Very rarely are the chemicals desirable in a modern society made in a single step. Indeed, it is not unusual for a drug to require at least 10 distinct processes. Conventional batch synthesis can often put a considerable burden on the efficiency of these steps, demanding excess chemicals and solvents and generating large and unacceptable quantities of waste materials. 

Now, a team led by Steven Ley at the University of Cambridge are advocating a more machine-assisted approach, particularly using flow chemistry techniques combined with scavenger materials to bring about multi-step operations with in-line purification. 

To find out more, read the full news story in Chemistry World and download Ley’s Edge article for free from Chemical Science.

Also of interest:
Unclogging the problems of flow chemistry: US scientists have found a way to stop solid by-products clogging channels in continuous flow reactors

Singlet carbenes can be used to isolate elusive neutral phosphorus radicals in the solid state, researchers have discovered. 

Very few phosphorus radicals have been isolated and characterised in the solid state because they tend to dimerise. Now, Guy Bertrand and colleagues have reported two phosphorus radicals, one stabilised by a transition metal and the other stabilised by N-heterocyclic carbenes (NHCs), which allowed them to compare the electronic effects of both substituents. While the transition metal was better at delocalising the spin density from the phosphorus nucleus, NHCs are sufficiently stabilising to allow isolation and characterisation of the neutral radical.

Download Bertrand’s Edge article from Chemical Science to read more.