A Taxol synthesis is simple

I got the results back from NSF fellowship application today. I didn't get the fellowship, but that doesn't matter. Something funny was that one of the reviewers said my “proposed project looked simple or at least written that way.”

I’m the chump working on the taxane project. The overall goal is in the figure below. You might have seen the Nature Chemistry paper where we described the construction of the taxane skeleton. My project involves multiple C-H oxidation transformations on this skeleton en route to Taxol. Simple, right?

I’m not here to toot my own horn or rally up a pity party, but I think every chemist familiar with synthetic organic chemistry will agree this endeavor is somewhere between crazy difficult and flat-out impossible. No one would claim it looks simple. Then why is this NSF reviewer judging my application if they don’t see the difficulty of this project?

To be clear, I wouldn't care if I scored “excellent” on everything and still didn't get the fellowship. There are many people deserving of this award, and who am I to say I deserve it more than anyone else? Also, there are plenty of reasons to not fund me or this project. My problem is that reviewers are unqualified to judge my “intellectual merit” if they don’t know the basic frontiers of my field. I guess the moral of the story is don’t assume people know why your science is hard. Be very explicit. This problem probably applies to some extent to other award applications and even applying for a job.

Column Chromatography....seems silly now.

Last month the team at Eisai responsible for the commercial scale synthesis of Halaven (easily the most complex drug molecule produced entirely by chemical synthesis) published a series of papers (theres three links there) detailing the development from the medchem route to process.  While these papers are a must read from the standpoint of using total synthesis to solve a supply need, this post is only peripherally related.

Early on in the synthesis of one of the pieces of the western half of the molecule the group does a chromatographic resolution of a racemic alcohol using 'simulated moving bed chromatography'.

Mechanism Mar. 16, 2013

Solution after the jump!

The Press Corpse

The press scribble scribble every half-truth spoke then shoot it round the country like an April Fools joke

Why not a semisynthesis?

What is a typical experiment in the Baran lab?

Ever wonder what a jelly bean does in organic solvent? Now we know.

Happy International Women's Day!

In honor of International Women’s Day I decided to post about what it’s like to be a woman in the Baran laboratory.  I was put up to this by my male peers.  I am currently the only female graduate student; we also have two female post-docs (who are awesome).  On an average day, I actively ignore sexist remarks made by insensitive colleagues, endure creepy co-workers in my lab hitting on me, and politely decline flagrant displays of male chauvinism cleverly disguised as chivalry when peers offer to bring the 20 liter of chloroform up from the first floor to the fourth.  Just kidding: the first case never happens, the second case only happened for the first few months and the third case, well, I let them carry up the chloroform.  

Too Much Time On My Hands

What YOU think of Phil Baran

Woe-Be-Gone

We'll start things off with our lab's recent synthesis of ouabagenin. We'll skip the biological relevance of the molecule for the purpose of this blog and go straight to the actual synthesis.