Total Synthesis: the String Theory of Chemistry
Introduction:
- still, it is not often that we find Art in Science. Although, as humans, we can argue that every piece of work is an art, be it setting up a reaction or writing a screenplay. But, let's cut the crap okay, there is no aesthetics in doing pages of calculations on the solution of Schrodinger equation or finding out the local minima of potential surfaces in a multidimensional space.The very definition of Art is rooted in the fact that it demands an appreciation of its creative beauty. It is what you feel after reading a Rumi poem, or when you marvel at a da Vinci masterpiece. And that feeling is not always easily found in science, except a few cases. And those cases are the topic of this introduction.
Before I go further, just for the sake of clarity, let's make a layman's list of 'what constitutes an art'.
Identifying traits of an Art:
- You appreciate it naturally, especially more when you understand it
- Often hard to understand, especially due to the complexity
- It provides you with an ecstatic feeling, you feel joy and wonder
- It may not be "important" to the "technological advancement", i.e., it does not have much value apart from aesthetics.
Calabi-Yau world:
But unfortunately, as hard as it is to understand, like one of those Picasso paintings, it has almost no value to the real physical world. Well, it has supersymmetry (much like Superman - the suffix exists, the prefix does not), 10 freaking dimensions and one Ed Witten (who exists btw), but it does not have a single prediction that can be tested practically to check its validity.
So basically we don't know if String Theory is true at all. Period.
This is the scenario for more than half a century now. And as a result, funding in string theory research is going down faster than a black hole's gravitational pull.
In a way, if you think, it is the biggest irony in the face of science. A field that requires knowledge of almost every other field does not have any practical value. Classy!
But, String Theory is more successful at being an Art. It fulfills all the criteria we listed above. Well, I am not assuming you understand it, but at least you get the feeling from those who do. To them, it is like having a copy of Tagore's "Songs Offerings" or Elliot's "Four Quartets" - as a source of joy and inspiration behind their own works.
But, then you can ask the obvious question, "Why do actually people take up String Theory as a career option? Isn't it a dead end for a career?"
The answer would have been different some 20 years ago but now it's pretty clear for the present generation. One of my friend's brother is currently doing a Ph.D. in the US. Once I asked him, why did he choose String Theory? And his reply was quite pragmatic, (unlike the theory itself).
He told me that he is pursuing String Theory because he can switch to another related theoretical field if he wants. The depth of mathematical techniques and broad knowledge needed to do string theory makes one capable of doing almost all the other related field with more promise. So, not a bad strategy in that way.
The cherry on top of chemistry-cake:
You may be a bit confused by now. Isn't it supposed to be a blog about chemistry? why we are talking about some overhyped 10-dimensional weird theory and not about chem? Okay, let me break it to you ...Total Synthesis is the string theory of chemistry. Only with less dimensions and more productivity.Yeah, it may sound completely unrelated but you get it if you think clearly and compare them. Though still I have to clarify the claim, and I will do so in some future post where I will exclusively talk about Total Synthesis, but for now, my sole aim is to establish the connection between Art and the 'Art of total synthesis' (Or the 'Science of Total Synthesis', I don't know).
Total Synthesis, a.k.a. Natural Product Synthesis is the science/art of constructing complex natural molecules at the lab using the chemical transformation techniques available to a chemist. Actually, this is the job of Nature. But we cannot simply put down the urge to compete with the Ultimate Architect. Well, that was not entirely true, we actually need total synthesis to make biological and other important molecules artificially. It requires the knowledge of almost all fields of chemistry and beyond. It may be hard for you to justify why I claimed string theory to be an art, but you can certainly be sure about that for total synthesis.
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| Strychnine: The most complex molecule known in 1952. |
Let's take an example. This is the notorious mass murderer Strychnine (black). Widely used in detective stories as a weapon of murder, it's an alkaloid toxin. Its structure was first discovered by Nobel Laureate Sir Robert Robinson et al. in 1946. In 1952, Sir Robinson declared it t be "the most complex substance known". Now, imagine yourself to be a chemist in 1952 who cannot but wonder, how the hell can someone ('Nature') make such a horrible structure? And the next thing you know, it is your job to recreate that molecule at the lab (If you were Woodward, you were going to do it in 1954 anyway). Here's the competition against nature, to claim that you can make such molecules too, not Her alone. That requires creativity, persistence, and mastery of all over chemistry.
It is a scientist's way to become an artist.
The Challenge:
You must be knowing that it is hard to create stereogenic centers in the lab, as most planar structures result into recemic mixtures. Now, look at the molecule above. Palytoxin. See how many freaking stereogenic centers it has? 64 - f*** ! can you imagine! All we have done are easy organic conversions like from ethane to methane, acetone to paracetamol etc, if you are too much into it, you also might have done formalin to coumarin, but now imagine someone told you to do coumarin to palytoxin ... would you dare?
Literally, the total synthesis of palytoxin by Yoshito Kishi et al. was titled as "the Mount Everest of organic synthesis, the largest single molecule that anyone has ever even thought about making".
Today, with much more techniques available at hand, you can imagine what a remarkable feat it was long back when Woodward synthesized Reserpine in 1958 with just Diels-Alder reaction to set up 5 out of 6 chiral centers. He was eventually awarded the Nobel prize in 1965, not for any particular reaction or molecule but "for his outstanding achievements in the art of organic synthesis".
Conclusion:
Although it still considers electrons as point particles, Total Synthesis is the exact parallel of string theory in chemistry. Only it has much more practical applications in several fields like drug development, medicinal chemistry and development of synthetic methodologies etc. But still, there is an ongoing hot debate on whether total synthesis has reached its dead end. Only two Nobel prizes have so far been awarded in the field and of which the last one was almost 30 years ago. Fundings are at a downfall, even for the best synthetic chemist out there. And so, much like string theory, people trained in total synthesis are leaving and joining other related fields due to their mastery over other topics.
But still, most of us believe that Total Synthesis is still as exciting as ever with still a lot more potential. And it is our duty as chemistry-lovers to bring about its golden age. We need to embrace modern technologies and build our creativity on top of it. It is time to combine art and science together.
Patient: Total Synthesis
Age: 190
Father: Friedrich Wohler (1828)
Mentors: R. B. Woodward, E. J. Corey
Relatives: Nicolaou, MacMillan, Baran, Stoltz etc.
Diagnosis: Existential Crisis
Doctors: Next generation chemists - Us
P.S. - Patient is from the universe C-137. String theory hasn't yet created worm-holes there.
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