Probably the only total synthesis I'll ever mention

First, let me say this: I am NOT a total synthetic chemist. I find synthesis qua synthesis, or synthesis for its own sake, to be boring. You could argue for hours about the utility of total synthesis or (worse) argue whether certain syntheses are "creative" or "elegant" or whatever, and usually such arguments make me want to dillyslap people with something silicone-based. (On the other hand, people do this all the time at Totally Synthetic, which, like a train wreck, I read religiously every post and every futile argument about whether that cross-metathesis was really a creative way to perform that particular cyclization since Porco did it in 2004 in his now-famous synthesis of spongeotoxydeathylene.) As such, I usually skip the total synthesis ASAP papers and stick to getting my tot. syn. info from Tot. Syn.'s excellent blog.

But here's a total synthesis that, somehow, the good people (guy?) at Tot. Syn. missed. I had completely forgotten about this one that came out about a month ago until the authors published an addendum (forgot to add some funding people in the article), and forgotten how excited I was that I was finally able to comprehend easily the landmark Org. Lett. six-step total synthesis of S-equol by the Boulanger group. With Four linear steps! Talk about pushing the boundaries of the definition of total synthesis. Nicolaou Woodward must be rolling in his grave right now. Granted, the group claims this is the first enantioselective, large-scale synthesis of this molecule which is of interest to breast cancer researchers. It has one stereocenter which is affixed enantioselectively via an Evans alkylation, and the cyclization is done via a Buchwald etherification. The whole thing is kinda neat, I guess, but I wonder why this particular synthesis is important enough to warrant publishing in a journal dedicated to the latest and greatest in organic synthesis and methodology.

This synthesis is the inspiration for Excimer's Rule for Total Synthesis.

If I can make it on paper, it's not a total synthesis.

Maybe I'm just underestimating my skillz in synthesis (psh), but I think I'll just stick to nanocrap for now. Back to your regularly scheduled pretty colors and neat materials next time.


ElwoodCity said...

It isn't a "total synthesis" in the Woodward/Nicolou tradition, but when they way it is large scale, keep in mind that they are a contract synthesis company. This is a synthesis that is guaranteed to work cheap/efficiently. I'll take that before the over-engineered "elegant" methods from sponge extract synthesis, anyday.

Organic Chemistry said...

I would argue that it would be a total synthesis in the pharmaceutical sense of cheap/fast/efficient.