This is a post that I can take no credit for as it is my first guest post. It’s also the post I wish I had read before I started my chemistry degree as it would have crystallised the link between organic chemistry and natural products. As I say to pupils the link between the medicine men of the South American jungles and the drugs that we are prescribed is closer than we could ever realise, anyway over to the ‘organic chemist’ ……….
There’s a branch of organic chemistry that focusses on the synthesis of highly complex naturally occurring compounds. “Natural product synthesis” (as it’s referred to in the field) is a long established discipline that is both highly regarded and more recently somewhat divisive amongst organic chemists. It’s not unusual for the synthesis of a complex natural product to take several years – typically consuming one (or many) student’s entire PhD tenures (typically 4 years!).
Probably the most extreme example of human endeavour in the field of natural product synthesis is that of the synthesis of vitamin B12. This synthesis of this molecule took no less than 12 years and was accomplished collaboratively by 91 post-doctoral researchers and 12 PhD students from 19 different nations. Accomplishments such as this of course receive the accolades they deserve but there also exists a contrarian viewpoint that asks the general question, “why would anyone want to spend such much time, effort and money making molecules that generally have no current applications in the real world?” (There’s no need to make vitamin B12, it’s in our food!!). Parallel viewpoints like this can of course be expressed outside organic chemistry: “Why would any sane person ever want to climb Mt Everest?”; “Why did mankind think it necessary to spend billions of dollars putting men on the moon?”; “Why are we seriously considering sending humans to Mars given the cost and risks?” The argument to counter all of the above viewpoints (whilst difficult to justify before the completion of whatever heroic task is being undertaken) is that the things we learn from tackling the most difficult, complex, dangerous and costly problems often will have indirect benefits that will hopefully advance/sustain humankind (and our planet) in the decades and centuries to follow. For example, climbing Everest has taught us a lot about human endurance under extreme conditions and how sustained hypoxic (low oxygen) conditions affect human physiology (especially with respect to congestive heart failure and sleep apnea). These findings have then been applied in the real world.
As for natural product synthesis and those labs that specialize in this discipline, the direct and indirect benefits are multitude: not only do these labs offer an amazing environment in which the industrial and pharmaceutical chemists of the future learn their trades but new discoveries along the way lead to new general synthetic methodologies that benefit all of the organic chemistry community (and beyond…). Having a portion of academic organic chemistry research dedicated to natural product synthesis is on balance probably a good thing even if detractors think it outdated. The benefits of spending 10 years making “nobodycaresomycin A” might not be immediate but somewhere down the line a use for this product (or methods of making it) might be realized (and millions of Japanese sea slugs won’t suffer the fate of being squashed and extracted to isolate 0.5g of compound!).
No post about the synthesis of complex molecules would be complete without mention of a titan in this field, Robert Burns (RB) Woodward (1917-1979). Undoubtedly one of the greatest organic chemists of all time (some would argue the greatest) he forged the field of complex natural product synthesis at Harvard University and synthesized fantastically complex molecules including: vitamin B12, quinine, cholesterol, cortisone, strychnine, lysergic acid, reserpine, cephalosporin C and chlorophyll but to name a few. These achievements not only represent the pinnacles of synthetic methodology and practice but many are important molecules that have advanced human health immeasurably.
Not only a Nobel Prize winning chemist (in 1965) but Woodward was a true character to boot. An always dapper man his Thursday evening lectures were legendary – known to last for 3-4 hours at a time, chain-smoking cigarettes whilst drawing exquisitely beautiful complex structures from memory in coloured chalk (such were the epic nature of his lectures his students developed a measurement for the length of these sessions in units of so-called “milli-Woodwards”!). His lectures were characteristically clear, original and insightful – starting at the upper left hand corner of a large blackboard and finishing at the bottom right hand corner with precise logic. Understandably (and sadly) only parts of a few of his lectures were ever recorded for our enjoyment. He loved the colour blue – from his suits to his parking space being painted blue at Harvard (on which was parked his blue Mercedes…). He was very partial to Scotch or maybe a Daiquiri (usually ordered two at a time…).
Many have observed that his methodologies and syntheses have an element of artistic elegance to them in addition to stellar science. Such was Woodward’s breadth and depth of chemical expertise that he most likely would have obtained a second Nobel Prize in chemistry in 1981 had he been alive (the 1981 Nobel Prize was awarded for studies into the nature of chemical reactions). His contributions to organic chemistry (beyond the ability to purely make something) are important, vast and enduring. Woodward died in his sleep on 8 Jul 1962 (aged 62), no doubt deep in the dreams of his next synthetic adventure.
“A scientist has to work very hard to get to the point where he can be lucky.” – RB Woodward.