B.R.S.M. Help! I'm trapped in a molecule factory!

23Jun/111

Solanoeclepin A

Total Synthesis of Solanoeclepin A

K. Tanino et al., Nature Chemistry, 2011, 3, 484–488; [PDF] [SI] [GROUP]

DOI: 10.1038/nchem.1044

Admittedly I don't check Nature Chemistry as often as I should, so I only noticed this truly epic synthesis of solanoeclepin A a few days ago. I remember being shocked by my first sight of the structure during a talk by Prof. Henk Hiemstra a couple of years back, especially that improbable looking DEF ring system. This synthesis is obviously a phenomenal technical achievement, and it must have been an incredibly demanding task, but at first glance there aren't too many sexy steps.[1] The abstract mentions 'addressing one of the critical food issues of the twenty-first century' and solving natural supply problems, goals towards which this synthesis could be the first step.[2]

I'd imagine that when attempting a synthesis of this complexity you'd want to stick as closely as you could to well established chemistry that can be performed on large scale, so I was surprised to see this nice little cross coupling around step 30:

I had no idea you could do this (although the methodology is older than I am), and even if I did, I probably wouldn't plan it in the middle of a 50+ step total synthesis! The method was originally described with aryl bromides and a range of silyl enol ethers, and although even the yields in the seminal paper are a bit so-so (50-65%), any alternative sequence I can think of is quite a bit longer. The α,β-unsaturated ketone is then immediately used as the dienophile for the intramolecular Diels-Alder reaction which forges the A,B and C rings. Wow. Just wow.

 

[1] A great organic chemist once told me that every synthesis should have at least one 'sexy step'.

[2] By my calculations every 10g of that not-so-readily available starting material gives 41 mg of the natural product. A little goes a long way, though, as it's active at down to 10^-10 g/mL in water.

 

Comments (1) Trackbacks (1)
  1. Hey! Not been here before….great stop in. I totally agree with the “sexy step” of any given synthesis…you wouldn’t want to read if it’s all just hammering on.


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