What would Woodward do ?

This is a post appearing in Sep ’07 on the late lamented first incarnation of ChemBark (which I don’t think can be accessed any more).  It was kicked up by the latest post on “The Curious Wavefunction”  http://wavefunction.fieldofscience.com/2011/02/note-on-cultish-status-of-organic.html.

Sleeper is one of the great Woody Allen movies from the 70s.  Woody plays Miles Monroe, the owner of (what else?) a health food store who through some medical mishap is frozen in nitrogen and is awakened 200 years later.  He finds that scientific research has shown that cigarettes and fats are good for you.  A McDonald’s restaurant is shown with a sign “Over 795 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 Served”

Rip returned from the 100 year birthday blowout and band camp and began attacking a giant pile of accumulated unread journals.  In the 9 August Nature (p. 630 – 631) he was amazed to read criticism of a 64 step 22 year synthesis of an exquisitely complex molecule (azadirachtin) — a molecule in which it is easier to count the number of optically INactive carbons than the optically active ones.  Back in the 60s we were all impressed with how Woodward got the 5 asymmetric centers in a 6 membered ring of reserpine (which was in use as an antihypertensive at the time, and whose fairly common side effect of depression was one of the clues leading to the amine theory of affect).  Rip was surprised to find that the criticism was not that the synthesis was incorrect, but that the project shouldn’t have been done at all.  Apparently a significant body of organic chemists think this way.

Political correctness has left few groups which it is safe to disparage.  With apologies to one of them (Christians) I’ve got to ask “What would Woodward do?”

Rip’s father went into the hospital shortly after his 100th, and is getting out 1 Sep, so it may be a while before he can respond to what this post brings forth.


The Nature article kicked up a lot of commentary, a lot of which appeared on The Wall, interestingly enough starting about the time I sent post #7 in to Paul (30 August) so I’ll respond to the stuff in the Wall in this post

Some of the correspondents (Eugene # 178) imply that some of the anger against total synthesis is because funding is finite and TS is getting too much, depriving worthier efforts in chemistry.  Joel #217 says this more explicitly “We ascribe intrinsic value to the different disciplines because there are finite resources to pursue them. People are not arguing for the end of total synthesis, just a lessening of the emphasis in terms of funds and manpower”.

This is a battle that is fought in all scientific fields (look at the abandoned supercollider in high energy physics, the cancer genome atlas — critical letters can be found on this [ Science vol. 315 pp. 762 – 764 ’07 ], etc. etc.). I have no way of knowing if this is true of organic chemistry or not, but as a reader of Science and Nature for the past 40 years or so, there has NEVER been a time where funding has thought to be adequate, where dire imprecations about the future of science (American English, you name it) due to inadequate funding were not made.Meanwhile the scientific enterprise has lept from strength to strength.

Eugene also says (#208) “Of course another benefit of total synthesis is being pushed to your physical and mental limits by working like an indentured servant for four years.” This sounds like the internship.The time to learn that you can stay up all night and the next day taking care of a critically ill patient, is NOT when you are on your own in solo practice, but early in your training, so that when you are by yourself doing the same thing, you don’t have to wonder if you can do such a thing.

TheEdge (#214) says something I think is quite important and which I’ll come back to in a future post “I think that most totsyn chemists undertake their projects for two reasons: to test their understanding of chemical reactivity, — “.Willyoubemine #220 — says the same thing, in greater detail and perhaps more eloquently.

I’ve read no total synthesis papers since the 60s, so I don’t know if what he says “Total synthesis should be the chemistry equivalent of taking an in vitro study and running it in vivo, but our papers are rarely written like that, and people get the impression that we’re doing it to prove how macho we are.” is true.Certainly mathematical papers are written like that — all the false steps aren’t mentioned, and how the idea of the proof was arrived at is never mentioned.It started with Euclid and was reinforced by Gauss.

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