Tag Archives: terpene oxidation

Soaking up Sponges

Fujita continues to broaden the applications of his wonderful new x-ray methodology, “The Crystalline Sponge” method. I’ve posted about this before and already said it is a game changer for all aspects of organic chemistry. This time Fujita has determined the crystal structures of oxidation products of α-humulene.


He treated this sesquiterpene with various equivalents of m-CPBA and separated the products by chromatography. For example 1 equiv. gave 3 mono-epoxide products and as expected 2 and 3 equivs gave bis and tri-epoxides respectively. He also oxidised with selenium dioxide separated  and obtained regioisomeric allylic oxidation products (aldehydes). Just to finish this all off he used the chiral oxidation system of Shi (from Organic Synthesis) to obtain chiral epoxides. The chemical results are very interesting but the method used for the crystal structure determination is extremely so.

Using the well tried [(ZnI2)3 (tpt)2 x(cyclohexane)]n (tpt = 1,3,5-tris(4-pyridyl)triazine) as the crystalline sponge, crystals of humulene were x-rayed. Now the crystal sizes of the sponge are 230 x 170 x 80 μm! A 5 μg sample of humulene were adsorbed into the sponge. This is interesting in itself as this compound is an oil and apparently it’s structure at rt has not been determined. After oxidation similar product amounts were analysed. In total there are 10 structures presented in this paper. It is also worthwhile to note that they detected an impurity in the products, impurity detection by x-ray. It turned out to be  Bis(2-ethylhexyl)phthalate, a plasticiser!!

Now I’m not a crystallographer so the author’s comment (sorry for the length) seems appropriate here “In summary, all the structures of the oxidation products of parent compound 1, including their relative and absolute stereochemical configurations, were successfully determined using the crystalline sponge method. All the measurements were performed with only microgram quantities of the compounds. These experiments brought us not only structural information but also several lessons on using the crystalline sponge method for analysis. First, we clearly demonstrated that if a parent compound fits the sponge pore, its scaffold- related derivatives are also likely to be good substrates. Second, we found that the guest-binding site for the derivatives may be different from that of the original molecule if the derivatives find better binding sites as a result of additional host–guest interactions in the pore (for example, by hydrogen bonding with the host framework). Third, it is clear that careful consideration is necessary when discussing stable conformations based on these crystal structures because the guest conformation is biased by host–guest interactions in the crystalline sponge. Our method can provide highly valuable information on incorporated molecular scaffolds, such as functional group position, stereochemistry, and the 3D molecular arrangement. We expect that the crystalline sponge method, even considering its limitations, will significantly accelerate both synthetic research and drug discovery.

Now I completely agree with them. This is a wonderful method (in spite of recent criticisms) which Fujita has so convincingly demonstrated with this paper. So the recent comment in Nature news about this methodology failing to deliver is absolute bullcrap.

I wonder what else Fujita has up his sleeve, or in his sponge, we shall see.


5,612 total views, no views today