Process development and scale-up isn’t one of those things a young, freshly minted synthesis chemist generally aims for.  I recall the heady days in grad school when we thought “drug design” was the ultimate gig for a synthetic organic chemist.  Landing a slot in a first tier pharmaceutical discovery group was like landing a spot on the cast of a Broadway play.  And, in fact it is like that.  I have many friends and fellow students who have found fantastic careers doing just such a thing.

In the late 80’s and early 90’s, asymmetric synthesis was hitting its stride and anyone who could make heterocycles with chiral shrubbery attached somewhere was golden. Even better, if you had studied “Enzymatic Reaction Mechanisms” by Christopher Walsh and you could name all of the amino acids, you definitely had a future.  Most of us were lucky to be able to pronounce propinquity after consuming four pounds of Killians after a long day of research.

This time period that I refer to is before the introduction of high throughput experimentation (HTE), or CombiChem.  It was a kind of gilded age where reductionists prevailed.  If only we had enough data on the geometry of the active site, we could design a suicide substrate inhibitor to shut the enzyme down. We had CAChe(R) and SAR to help with the design of pharmacophores- it was a heady time.

It was an age when giants walked the laboratories- Corey, Evans, Nakanishi, Seebach, Oppolzer, Meyers, etc.  Some of these fellows still do.  But things would fundamentally change when a new experimental methodology rolled into town. The age of automation had arrived.

HTE would spawn new ways of thinking in discovery.  To methyl, ethyl, butyl, … futyl would be attached an exponent.  It would become possible to do and analyze a thousand reactions in a day.  Pharma companies invested heavily in this technology and, I understand, some of it is actually paying off.

But while the elite discovery krewes were spending down these giant R&D budgets that exceeded the GNP of a third world nation, a different group was quietly laboring with that most favored transformation of all.  Actually turning chemicals into money.  The most prized alchemy.

The activity to which I refer is, of course, process development and scale-up.  This field requires a slightly different mind-set.  It is not the domain of the show-horse. It is the world of the plow horse. And, by the prinicple of propinquity, I have developed a taste for it. 

More to follow.