Is total synthesis the way to go?

[stellaparallax]

Hi guys,

 

I graduated from a Medicinal Chem major a couple of years ago and have finally decided thatI'm ready to go back and complete a PhD. Although my final year research project was a synthetic bioconjugate oriented project, and my current job is focused biochemistry, I've decided that I heart lies with synthetic organic chemistry as I personally find this the most enjoyable area in terms of research. 

 

So now I'm faced with the difficult problem of choosing a project... I'm not too fussy, I just want to give myself the best chance of at acquiring a vast range of synthetic techniques in the 3-4 yrs that I'll be studying for. Although I'd probably find a med chem oriented project a little bit more interesting, I'm currently under the impression that a natural product total synthesis project would be the best way of learning the most synthetic skills... am I right in thinking this? Would I be more attractive to employers (academic and/or industry) if I had total synthesis experience?

 

Thanks for your help and I apologise for my naivety If I come across that way 

[St Andrews Lynx]

Total synthesis isn't all that fashionable these days. The vast majority of the "pure" total synthesis groups I've seen are struggling to obtain funding. Making small molecules or designing new reactions is a lot more lucrative. 

[stellaparallax]

Even if it is unpopular, would I be learning more skills in a total synth project rather than a med chem project that primarily involves exploring structure-activity relationships?

[Eigen]

If those are your only two options, then yes, you'd learn more synthesis with the total synth project. 

 

Those are rarely your only two options, though. 

 

Honestly, total synthesis may or may not get you a lot of diversity in technique- it can also just be years optimizing the same reaction. You might learn a lot of techniques, or you might get really, really good at one or two niche reactions and techniques. 

 

A lot of non-total synth organic groups will have a good range of synthetic approaches, imo. 

 

But no, I don't think you'll be "more attractive" to employers with a total synth background. 

[synorg]

It depends on what you want to do with your career. A friend of mine in my program worked at Merck before coming to grad school and she said that they heavily favored applicants with total synthesis backgrounds over their methodology-focused counterparts. Funding in the labs is the most legitimate concern addressed so far. Unless you're at a top group, you're probably going to be severely limited in what you can work on. Low hanging fruit in total synthesis is a waste of time and only serves to give ammunition to those who wish to eradicate the field.

 

As for what Eigen said, there is a large benefit in the breadth of chemistry that you become exposed to. There are also times, however, where you beat your head against a wall over one reaction for a long time. That type of hurdle is fairly general to the grad school experience, though, and not unique to total synthesis. 

 

If choosing between TS and Methods, I'd go TS all the way. Methods involves very little learning. You buy almost all of your material, and if you have to make a substrate, you probably never care about the yield. You screen the shit out of every metal source and ligand you can get your hands on. Not a lot of synthetic technique required.

 

But for learning more techniques, TS a good move (unless you're working on a stupid molecule where the only stereocenter you set is done with an enzymatic resolution - a laughable post-doc application to my lab). For industry, it will help. For academics, your advisor/institution matter the most. Publications (many and high-impact) are obviously needed.

 

Good luck!

[St Andrews Lynx]

If choosing between TS and Methods, I'd go TS all the way. Methods involves very little learning. You buy almost all of your material, and if you have to make a substrate, you probably never care about the yield. You screen the shit out of every metal source and ligand you can get your hands on. Not a lot of synthetic technique required.

Not all methodology groups work in that way (i.e, as glorified reaction assays). 

 

In my group we have to synthesise a lot of our substrates and catalysts. As we develop a new reaction we've got to understand why it is working the way it is - often that requires a lot of intelligent control experiments and brain power. Methodology projects are shorter than a total synthesis project, so if you complete 2 or 3 smaller reaction methodology projects you will have been exposed to as much diversity as in a single total synthesis on say, an alkaloid.

 

On a more general note. You could have done the wildest, most innovative, 43-step total synthesis project and have ran all of Lazslo & Kurti's Named Reactions TWICE...but if you get to the job interview and are unable to sell yourself, then that job will go to the well-presented, personable Methodology graduate student who could really talk themselves up. Etc. 

 

Most "organic synthesis" labs have an overlap of total synthesis and methodology - go for those labs with the best balance. What I've seen of people who work in pharma is that they have a mixture of both total synthesis and methodology on their CV. 

[stellaparallax]

Hi guys,

 

Thanks for all you're responses, all your opinions have actually been really helpful! I feel much more confident with where I'm aiming for, cheers for that.

[Omar92]

So, what did you choose? :3