Chemical Science Blog

Spongistatin 1 is a highly cytotoxic natural product derived from a marine sponge.  In addition to its exquisite biological activity against human cancer cell lines, the structural complexity of spongistatin 1 has captured the imagination of several organic chemistry groups.

A number of total syntheses of the spongistatins exist, but more recently, simplified analogs of the natural products have been tested for anti-cancer activity.

In order to further probe the biological efficacy of simplified spongistatin analogs– or indeed, fragments– researchers at Columbia University have developed new methodology for the synthesis of the A-B fragment 3 and its merger to the C-D spiroketal fragment 3.

In their most recent Chemical Science Edge article, the Leighton research group have described a synthetic blueprint that could enable the synthesis and testing of a library of ‘C-D spiroketal-modified’ analogs of spongistatin 1.  Towards this overarching goal, Samuel Reznik was able to synthesise 34.5 g of fragment 3 in around 60 days; an achievement that demonstrates both the ‘scalability and step-economy’ of this synthetic route.

The Leighton group hope to apply this route to the synthesis of a series of C-D analogs and also hope to develop a complementary synthesis of the E-F fragment to further explore the anti-cancer therapeutic potential of spongistatin 1 derivatives.

Marilyn Monroe once sang that ‘diamonds are a girl’s best friend.’  If that is the case then it could be said that graphene, another form of carbon, has become the scientist’s best friend.  The relatively recent explosion of research conducted on graphene has been remarkable, and in 2010 resulted in a Nobel Prize for Andre Geim and Konstantin Novoselov at the University of Manchester.

Energy minimized structure from DFT calculations for a large PAH with the hydrogens removed.

Graphene can be thought of as the largest member of the polycyclic aromatic hydrocarbon (PAH) family, molecules made up of fused aromatic rings.  The interest in these carbon-based materials arises from their amazing electronic and optical properties.  The smaller members of the PAH family provide chemists an opportunity to create molecules of fixed and uniform dimensions, something which is challenging when making graphene.  Furthermore, by synthesising PAHs in a logical, stepwise fashion, we can adapt their properties to suit our own needs.

In a recent Chemical Science Edge article, the groups of Hexing Li (Shanghai Normal University) and Colin Nuckolls (Columbia University) have shown that they can construct large polycyclic aromatic hydrocarbons (PAHs) in a relatively straightforward and high yielding process. As might have been expected, such a large aromatic molecule is not particularly soluble but, emphasising the utility of their method, they are able to overcome this by adding groups to the molecule which make it more soluble.  The versatility of their approach will surely lead to the creation of even larger PAHs which will eventually serve to bridge the gap between these small molecules to the extended structures of graphene.

Interested in more?  Read this HOT Chem Sci Edge article now!

Supersized contorted aromatics
Shengxiong Xiao, Seok Ju Kang, Ying Wu, Seokhoon Ahn, Jong Bok Kim, Yueh-Lin Loo, Theo Siegrist, Michael L. Steigerwald, Hexing Li and Colin Nuckolls
Chem. Sci., 2013, 4, 2018-2023
DOI: 10.1039/C3SC50374G

Ruaraidh McIntosh is a guest web-writer for Chemical Science.  His research interests include supramolecular chemistry and catalysis.  When not working as a Research Fellow at Heriot-Watt University, Ruaraidh can usually be found in the kitchen where he has found a secondary application for his redoubtable skills in burning and profanity.

Chloride ions are central to many biological processes and measuring the concentration of chloride ions in biological fluids can help diagnose a number of diseases, including cystic fibrosis.

Scientists from the US have synthesised a squaraine rotaxane which can detect chloride ions via colorimetric naked eye detection and fluorescence. This is the first example of a ratiometric chloride sensor that emits in the deep red region.

Read the ‘HOT’ Chemical Science article for free:

Squaraine rotaxane shuttle as a ratiometric deep-red optical chloride sensor
Carleton G. Collins, Evan M. Peck, Patrick J. Kramer and Bradley D. Smith
Chem. Sci., 2013, DOI: 10.1039/C3SC50535A

Scientists in the US have prepared three UiO-68 network topology metal-organic frameworks (MOFs) using phosphorylurea substituted organic ligands and used them as sorbents to extract actinide elements from water and artificial sea water. 

The MOFs were shown to be highly efficient at sorbing uranyl ions, with saturation sorption capacities as high as 217 mg U g^-1 which is equivalent to binding one uranyl ion for every two sorbent groups.

In the future, the technology could be used to extract uranium from seawater for nuclear fuel production and for the removal of radionuclides from waste streams and drains at nuclear power plants.

Read this ‘HOT’ article for free for a limited period:

Highly porous and stable metal-organic frameworks for uranium extraction
Wenbin Lin , Michael Carboni , Carter Abney and Shubin Liu
Chem. Sci., 2013, DOI: 10.1039/C3SC50230A

Resiniferatoxin (1) and daphnetoxin (2) are members of the daphnane diterpenoids—a class of diterpenoid orthoester compounds, many of which exhibit fascinating therapeutic activity. Resiniferatoxin, whose total synthesis has been achieved only once, is a strong analgesic possessing a complex and densely functionalised tetracyclic core. Now, the Inoue research group at the University of Tokyo have used a series of radical reactions to construct the tetracyclic skeleton of the daphnane diterpenoids (3).

The first radical process was a 3-component coupling of a cyclopentanone (4), O,Se-acetal 5 and an allylstannane (6), and proceeded via a bridgehead radical generated from the reactive O,Se-acetal species. This impressive coupling assembled the A and C rings of the cyclic skeleton, forming 5 consecutive stereocentres in one step. These stereocentres were generated with high stereoselectivity with regards to the tertiary centres at C4 and C10, while the reaction was stereospecific for the creation of the tetrasubstituted C9 centre.

Subsequently, the researchers performed a 7-endo radical cyclisation of xanthate 8 in order to construct the 7-membered B ring. The protected daphnane diterpenoid skeleton (9) was produced as a single isomer with the desired stereochemistry at C8.

Tetracyclic skeleton 3 represents a common intermediate which, following functional group manipulations, would allow the synthesis of naturally-occurring daphnane diterpenoids, including resiniferatoxin, in addition to artificial analogues. The approach demonstrated by the Inoue group showcases the power of radical reactions in the formation of highly congested carbon frameworks and reinforces their relevance in the field of total synthesis.