A rare side of boron?

Synthetic chemists are good at creating conditions under which unstable molecules or intermediates can be generated and observed. George Olah’s 1994 Nobel Prize was largely due to his finding that low nucleophilicity media based on antimony chloride provides an environment where carbocations can live long enough to be detected. Under any other conditions, solvents are too nucleophilic to be innocent by-standers.

Now let’s talk about organoboron compounds, which are isoelectronic to carbocations. I just marvel at biological examples that demonstrate how electrophilic functional groups familiar to chemists are prevented from showing their expected properties. Boron in its trivalent form is electrophilic, which is the reason boron inhibitors developed by Anacor work as protease inhibitors. I blogged about these molecules a while back, on August 24. Earlier today I was interested to see a paper describing a recently disclosed Anacor’s structure that defies logic in that it shows a case where boron persists in its trivalent form and is caught in the act of inhibiting a ROCK2 kinase. While the binding mode at the hinge region is common for a kinase inhibitor, I am not aware of a synthetic variant of such hydrogen-bonded pattern involving a boron-containing functionality. As it stands, the fact that boron remains tricoordinate within the kinase active site, is quite unusual.



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