Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Climbing Mountains | Main | Imclone in Progress »

February 5, 2002

Why Total Synthesis?

Email This Entry

Posted by Derek

So why do huge natural product molecules still get made, if the thrill is gone?

Well, for one, not everyone agrees about the thrill. Total synthesis is one of the areas with real summits to plant flags on, and you really can be the first to climb them. And (unlike mountaineering!) you don't run out of mountains. They keep on coming, higher and trickier, year after year. Of course, as I went on about on Sunday, the technology keeps on improving, too. I'd argue that we're getting close to an expertise that allows us to hack our way up most any molecular mountain, one way or another.

Another reason the work goes on is that it used to be a great way to find totally new chemistry. Back in the day, you often had to invent new reactions just to have a chance of making these molecules, and that was one of the main justifications for the whole effort. Unfortunately, now that we don't necessarily have to invent the new reactions, many total-synthesis types don't.

I don't want to exaggerate, because it's still no cookbook. Many steps in a big total synthesis require lots of tricky modifications from the normal way you'd run a reaction. And there are lots of reactions that should work and don't; the first thing out of the book usually doesn't do the trick. But, still, very seldom now is new chemistry invented during a major synthesis. People will discover a new reaction, and think of a natural product to demonstrate it with, but they won't discover the new reaction in media res.

That's because it takes too long to do it. The advances in the science are making it gradually trickier to find totally new reactions, or new applications of old ones. If you're in a race to be the first to synthesize Megatoxin, you're not going to spend a few months (or a few years) to see if you can come up with a new reaction that'll save you six steps. You'll just hack out the six steps and get on with it - even if no one else is racing you, which is almost always the case these days.

There's one reason, though, that I can't argue with. Total synthesis is a great way to train chemists. You have non-stop problem-solving under very trying conditions, you experience all sorts of chemistry, and you end up with the hands to do just about any reaction there is. The drug companies love to hire total synthesis people. They figure (correctly) that dealing with the adversity of that work is good training for drug discovery, where most things don't work, either.

Comments (0) + TrackBacks (0) | Category: Chemical News


COMMENTS

EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
How Not to Do It: NMR Magnets
Allergan Escapes Valeant
Vytorin Actually Works
Fatalities at DuPont
The New York TImes on Drug Discovery
How Are Things at Princeton?
Phage-Derived Catalysts
Our Most Snorted-At Papers This Month. . .