Concise synthesis of pleurotin

From the perspective of chemists, pleurotin is an intriguing molecule.

There is strong evidence of untapped therapeutic properties as a tumor inhibitor and antibiotic. It has a fascinating complex structure (six rings! eight stereocenters!). And it has been difficult to synthesize over the decades. The last time chemists pulled that off, the year was 1988 and they needed 26 steps in which to do it.

For Princeton Chemistry’s Sorensen Lab, those qualities were part of the attraction for a long-term investment of time and energy that has come to fruition.

The lab reports a concise synthesis of pleurotin by way of the Diels-Alder reaction and a radical epimerization that flips a cis-hydrindane to the desired trans-hydrindane. Their late-stage intermediate intersects the milestone 1988 synthesis towards the end of the process, thereby reducing the total number of steps needed for the synthesis by thirteen.

The lab’s process could yield an expanded family of pleurotin-like anticancer screening candidates which, down the line, may be useful to pharmaceutical companies looking to exploit the promise of pleurotin as a next-generation drug.

“Pleurotin is a very sensitive molecule, it’s very reactive. But it hasn’t worked out as a drug yet, partly because it’s not very water-soluble,” said third-year graduate student John Hoskin, lead author on the paper. “Ideally you want to alter its structure: tweak here, change here, put a hydroxy here or a phosphate there, do some very careful modifications.

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