Drawn In By The Challenge!

The SCI-RSC National Retrosynthesis Competition is a well-established event that challenges the retrosynthetic and forward synthetic prowess of chemists across the UK from both academia and industry. This year’s challenge was to design a route to Swieteliacate S, a recently discovered novel phragmalin-type limonoid.

Already no strangers to success having been finalists six times in nine years, this year’s team, competing as The Barbierians, brought home a well-deserved second place.

Congratulations to Robin May, Yannic Werling, Ryan Inwood, Rayyan Miah, Robert Starley, Anas Buzrieda, Jerico Piper, Ciaran Archer and Jack Lowe.

We spent some time with Robin and Ryan who explained the challenges this competition presents and why that’s so rewarding.

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Congratulations! Second place, you must be very happy?

Yes, having been placed third two years ago we’re very pleased to achieve second this time round. It was a really great day getting to meet other chemists from across the industry, and yeah, a fantastic result.

‍Robin, what is it about the competition that made you want to enter?

I’m drawn in by the challenge of it as they are always very complicated molecules that mirror the complicated synthesis we do in our daily work for clients. You've really got to come up with some good ideas to solve it – you’re essentially trying to mimic nature. That's what I really enjoy.

‍Ryan, what’s the appeal for you?

It’s a really good proving ground to test your knowledge and you get to see a greater diversity of reactions than we would normally in our day-to-day work. It often takes an entire PhD to synthesise a natural product so the complexity is far beyond a typical small molecule therapeutic. It's also good to test your skills on molecules that are not streamlined or designed to be easy to make, which tests a lot of the fundamental organic chemistry knowledge you learn in academia.

‍Robin, you’ve described having ‘an odd way of approaching chemistry’, what do you mean?

Ha! Yes, this is perhaps a good example of that as we actually started in the middle of the route. We didn't look at the whole molecule and start where you normally would, by thinking of reactions. Instead we looked at the carbon skeleton and compared this to known natural product syntheses and found inspiration in the literature that let us jump into the middle.

What we found was a remarkable similarity between part of the Swieteliacate S skeleton and an intermediate used in the synthesis of (+)-cubitene. The key reaction we took from this was a Barbier macrocyclization reaction that made a 12 membered ring. We saw that, with a few modifications, we could use this Barbier reaction as a centring point in our route and build the whole thing from there.

It also gave us the basis for our team's name – The Barbierians – and, well, tradition dictates that a good pun is required (the puns are of course in-sulfur-able)!

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How did  this approach help when it came to the presentation at the final?

Yeah, it's probably what gave us quite a unique strategy and route in the end and that’s something the judges commented on. It was very creative, and we could see from the other teams’ presentations, it was very different, which we think is a good thing.

It made ours quite conceptually different as well. I always find it interesting to see how different chemists approach the same problem and all the teams had strong routes that we had to go up against.

When we looked in the literature, there was a well precedented northern half of the molecule and most teams made two fragments and brought them together with some interesting cyclizations. It’s one of the big challenges of the competition; do you stick closer to the literature or push the boat out a little? So, we think ours was conceptually very different and that helped us to stand out.

‍This is clearly a big team effort, how do you work together effectively?

Once the molecule was released the project team started to throw ideas out there and from this we could start to research and narrow down options. After a month or so we were able to get to a full route on paper. This year we settled on our idea quite quickly but in previous years it’s taken longer exploring two or three different ideas.

With the molecule being different each year we see the strengths of different team members come through. It makes it so enjoyable to be a part of as we’re learning from and challenging each other.

What we particularly enjoyed as a team is bringing together the experiences we have working in different teams and projects from discovery chemistry through to scale-up.

‍Are there learnings or skills from taking part in the competition that you can apply to your project work?

Absolutely! Although it’s not necessarily a specific idea what it does is contribute to maintaining our route scouting and synthesis skills. It gives you the opportunity to test your creativity and ability to overcome previously unseen challenges.

Even on long term projects we’re faced with different compounds that require a different approach each time. We had an example last year where a client’s current route wasn’t going to deliver what they wanted so we researched and suggested alternatives that would ensure they reached their goal. It’s pretty much the same approach as in the competition and so doing it helps keep us sharp.

Something else that the competition helps hone is how you present your ideas, again something that helps in our day-to-day work. You can have the greatest idea but if you can’t make it accessible to your audience or convince them it’s rigorous and backed up by literature your chances of convincing them it’s the correct approach can be slim.

‍So the presentation is as critical as the idea itself?

Absolutely! The competition is great for maintaining our route scouting and synthesis skills. It gives the opportunity to test our creativity and our ability to overcome previously unseen challenges.

Even on long term projects we’re faced with different compounds that require a different approach each time. We had an example last year where a client’s current route wasn’t going to deliver what they wanted so we researched and suggested alternatives that would ensure they reached their goal. It’s pretty much the same approach as in the competition and so doing it helps keep us sharp.

Something else that the competition helps hone is how you present your ideas, again something that helps in our day-to-day work. You can have the greatest idea but if you can’t make it accessible to your audience or persuade them it’s rigorous and backed up by literature your chances of convincing them it’s the correct approach can be slim.

‍Was there any specific feedback you took from the judges?

Our route was very much praised for its creativity and I think one of them even said it was fun, which is a funny way to describe chemistry but we liked that

‍That sounds like a perfect place to end, thank you for your time and we look forward to seeing you enter next year’s competition.

We’ve got our eye on first place so who knows the 13th competition could be lucky for us!

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