Monday, May 14, 2012

Baran Borole Begets Mess of Meroterpenoids

I know I'm preaching to the choir, but have you seen the latest from the Baran group?

Dr. Freddy probably said it best: Please, slow down, Phil!

In today's tract, Prof. Phil Baran and company search for a molecular linchpin, trying to stick a two-ring starting material onto an aromatic group. The resulting structures, dubbed meroterpenoids, show up in the framework of several marine natural products.

The group ID's a logical starting point: sclareolide, an essential oil isolated   from various species of sage plants. Long story short - the first few avenues (iodination, carboxylate degradation, BF3 salts) are all dead ends. The "Eureka!" moment comes when they try a cyclic borole (see right), which succeeds on multigram scale and produces a med-chem-friendly crystalline white solid. Using increasingly-popular radical conditions, Baran's team readily attaches this intermediate to benzoquinone (46-60% yield).

The result? A natural product, (+)-chromazonarol, formed in 34% yield... in only six steps! Mere mortals might have called it a day, but not Dr. Phil: he goes on to make nine more natural products, most of which had previously taken >12 steps to make on their own...not too shabby for a four-page Communication.

Boroles: All the things I've
come to remember...
Source: 1000 Eighties Blog
While reading this paper, I couldn't stop staring at the "borono-sclareolide" linchpin - now where had I seen that before? A-ha! It's the major attraction in all those antibacterial compounds Anacor recently developed. Perhaps, more entrepreneurial readers might consider calling to find out if Anacor's replete pipeline might suffer further functionalization, bringing forth even more wild drug leads.

1 comment:

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