Princeton University develops simple pleural protein synthesis technique

From a chemist's point of view, pleurin is an interesting molecul.

There is strong evidence of untapped therapeutic properties as a tumor suppressor and antibioti.

For the Sorensen Lab at the Princeton Institute of Chemistry, these qualities are part of what attracted them to put in so much time and effort and get result.

The laboratory reports the facile synthesis of the pleural protein cis-hydrindane to the desired trans-hydrindane by means of the Diels-Alder reaction and free radical enantiomerizatio.

The lab's process could lead to an expanded family of pleuroprotein anticancer screening drug candidates that could be helpful to pharmaceutical companies looking to harness pleuroproteins as next-generation drug.

"Pleurin is a very sensitive molecule, it's very activ.

"Because you can't really start with the pleuroprotein itself, our approach would be to incorporate changes from basal synthesis, which is only possible because of the shortness of the rout.

"When chemists look at structures like this, there isn't any obvious strategy for creating them from simple compound.

"If you take pleuroprotein, I want to do site-selective chemistry on the periphery of it, so we can build new molecules with better performance, and maybe better anticancer agent.

"Eight steps is quite a few steps for such a complex molecule," Sorensen sai.

Unfulfilled promises since 1947

Pleural proteins are derived from the fungus Pleurotus genu.

But because its synthesis is not easy, it has not yet reached its full potentia.

To reduce the number of synthetic steps, the researchers used a well-established strategy in organic synthesis called 5 hydrogen atom transfer, in which a reactive, oxygen-centered radical is essentially " cross over" and remove a hydrogen from the carbon belonging to the pleural structure, thereby generating a new free radica.

"We tried a lot of different strategies and ultimately succeeded, which was a reversal step of cis-hydrindane to trans-hydrindan.

This process produces a racemic final product that makes the left and right versions in equal proportion.
Only one of them may be biologically activ.
Now that the formal synthesis has been done in a more compact way, Hoskin said, the next challenge will be to produce just a mirror-image version of a molecule and its analog.

This study shows the power of brief synthesis," Hoskin sai.
"It only takes one week to complete the entire rout.
"

Sorensen added: "I think this work puts us in a good position to achieve the larger goal of expanding the class of anticancer drugs based on pleural protein.
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