From: Jack Sullivan (jsulliva$##$eclipse.net)
Date: Sat Feb 26 2000 - 13:33:07 EST
Michael B. Smith wrote:
>
> I can't let this one pass by.
>
> The idea that aspects of organic synthesis can be automated is clearly
> correct. That the automation will make it purely mechanical is an
> engineering philosophy that ignores three main points.
>
> 1. It assumes that all synthetic problems will be solved by known
> reactions. The history of synthesis shows that most molecules present
> unique challenges that defy programming based on known chemistry.
> Hence, someone must invent a new solution around the problem. This may
> mean backing up in the synthetic plan and try a new route; taking a
> completely different synthetic route; or, inventing a new reaction or
> process to solve the problem. The first two may be programmable - the
> third one is not.
>
> i..e. There is no such thing as a "standard unit" or a set of standard
> units in organic chemistry that are universally applicable.
>
> 2. It assumes we know enough about organic chemistry to anticipate
> every problem a priori. Anyone familiar with synthetic literature
> knows that this is not the case. Will it be in the future? Maybe! Even
> if we can anticipate every problem, I have serious doubts that all
> synthesis will be mechanical in the way they are executed.
>
> 3. Scale up, the EPA, and the FDA.
> We all know that just because something works on milligram scale,
> obtaining useful quantities is a major problem, and scale-up problems
> are not just engineering problems. It is not an accident that
> pharmaceutical companies place a lot of responsibility (and money) in
> the hands of process chemists who must often re-invent the synthesis
> to make it commercially useful. If we factor in the FDA requirement of
> purity, particularly for enantiopurity, diastereopurity, and metal
> content, these are not readily programmable. Likewise, concerns with
> the environment place further restrictions that are not always easily
> anticipated or solved a priori.
>
> Apart from this, there is the issue of why we do synthesis. Clearly,
> from an industrial viewpoint, we want the compound. From an academic
> standpoint, the goal of synthesis is to TRAIN scientists as much as it
> is to obtain the target. There is also the important goal of inventing
> new reactions and trying to understand organic chemistry at a higher
> level, which is shared by academic and industrial labs. Training
> scientists is not a software issue, it is an intellectual issue as
> well as one of learning the lab skills required.
>
> My final parting shot is simply that I have heard of the demise of
> synthetic organic chemistry for years. Synthetic chemistry is always
> on the decline-right to the point where people run out of material and
> do not know how to make it (or how to program things to get it).
>
> Cheers!
> Professor Michael B. Smith
> Department of Chemistry
> University of Connecticut
> 55 N. Eagleville Road, U-60
> Storrs, Connecticut USA 06269-3060
>
I have to disagree with Professor Smith's optimism about the future of
synthetic organic chemistry.
In a day of huge supercomputers like Blue Gene that are capable of
defeating human chess masters, the statement that organic chemistry
presents "unique challenges that defy programming" sounds more like
common attitudes 10 or 15 years ago about computers not being able to
better human chess whizzes. It also sounds a lot like the "irreducible
complexity" arguments used by creationists in point out structures like
the arthropod eye that could only have been created by an "intelligent
designer." With the accelerating rate of growth in computing power, we
are on shaky ground if we state that such and such will never be
programmable.
Reducing the huge literature of organic chemistry to a searchable data
base and applying libraries of known reactions to analyze and interpret
a proposed synthesis scheme is, as pointed out by Professor Smith, are
clearly workable schemes today. But the "invention" aspect is indeed
another matter.
"Invention," according to my Webster's dictionary, is defined as
"ingenuity or creativity" and "something thought up or mentally
fabricated." A human mind connects some facts and arrives at an insight,
a way around an obstacle to his desired solution. I see no a priori
reason why such cannot be programmed into the computer of the
not-too-distant future.
If the supercomputer can go through many thousands of possible moves and
their many-layered repurcussions in a few seconds, why can't such a
machine go through every possible transformation, both forward and
reverse? It could then eliminate the physically impossible (based on
programmed rules of the physics and electronics of atoms and atomic
constructs) and present the experimenter with a set of hypothetical
schemes for him to evaluate and perhaps select for actual lab
experimentation. (Fortunately, I still see the human researcher in the
loop between the supercomputer & the automated synthesizer).
Yes, problems will be encountered, just as they are today. Nature has a
way of defying prediction.
Who will own these computers? As Professor Smith points out, it will be
the major companies like Merck and Eli Lilly who need to address a
number of critical synthetic questions in the shortest possible period
of time. Every day that these firms waste in getting a new drug to the
market is millions of dollars lost to their top lines.
Yes, the universities still need to train chemists, and I see no end to
that process. But things have changed and will continue to change in the
universities as well, just as things that were done via mixed melting
points 100 years ago are now done by 300 MHz NMRs. But the accelerating
influence of computers will have an increasing impact on all segments of
organic chemistry training. I can see employment ads in C&ENews 5 or 10
years from now that will require proficiency in, among other things,
sophisticated computer-aided synthesis programs.
On a somewhat humorous final note, I recall a science fiction story by
the late Isaac Asimov in which the militarized world has been
computerized for so long that basic math skills had been lost through
disuse. But someone rediscovers addition, substraction, multiplication
and division, which is seen as a major breakthrough and tactical
advantage over the "enemy." I recall that story when I see young
students carrying sophisticated programmable calculators into exam
rooms. I sincerely hope that the organic chemists of the future do not
lose the fundamental skills of this great science.
-- Jack Sullivan __________________ORGLIST - Organic Chemistry Mailing List Website and Archive: http://www.orglist.net/ List coordinator: Joao Aires de Sousa (jas$##$mail.fct.unl.pt)
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