[kriggy]

Im not sure if this is org. chem question so feel free to move it.

I know some of you synthesize compounds which can be found in nature. Im bit curious about this topic so: How do you choose which compound(s) to synthesize?

[discodermolide]

Depends if you are in industry or academia.

[kriggy]

It doesnt realy matter, Im intersted in both. I guess in industry its driven by the possibility of having some aplication which can earn money.

[discodermolide]

That's very true.
In academia selecting a target could be done in a number of ways. Through collaboration (funding) with a company, then you may be a bit restricted in the choice.
You may have also developed new chemistry in your lab and are looking for a use for it.
You may be interested in a particular area of natural products, i.e. a certain biological activity, challenging synthesis and so on. Then you need to get your ideas funded, grant proposals.
Some academics have continued along a path they followed as a student or post-doc. So it really depends a lot upon your interests.

[AlphaScent]

@disco has pretty much hit the nail on the head.

I would say that some people believe their study of a particular section of natural products is more important than another.  I had a professor who put down my advising professor because he only did insect pheromone research, where as he did sterols.  I ended up staying with my adviser for 2 more years through undergrad and started a job synthesizing these pheromones on a daily basis.  It is possible to bridge academia and industry but it is not always the case.

I would have to say research in academia is far more favorable to industry because of the error that is tolerated.  I should say lack of results, not error. 

I will say this and it is to my detriment.  I synthesize these pheromones with almost no interest in the entomology that makes my science possible.  Natural products chemists I feel ultimately do it for the chemistry, not the source of the material.

My 2 cents.

[zsinger]

Simple……We find a compound (sometimes serendipitously such as acetylsalicylic acid…well a derivative anyways), elucidate its structure through our tools such as NMR, IR, and then we think about our toolbox of reactions that make such connectivities possible.  Some are darn near impossible to carry out, as they require biochemicals which are either endogenously produced, or uber expensive for a one gram sample.  Some are not….take the aspirin example listed above.  Simply adding acetic anhydride to salicylic acid yields aspirin.  Hope this helps.
                  -Z

[discodermolide]

Hi Alpha.
The synthesis of insect pheromones is a great way to learn about organic synthesis. Plus you have the added effect of watching the effect on the insects, which, if the pheromone controls their growth, for example, is a great way to apply the research that you do for mutual benefit (unless you happen to be an insect of course). So I think you win all the way with this topic, enjoy it.

[AlphaScent]

Hey Disco,

I do agree that it is a great way to learn and employ various synthetic techniques.  That is why I do enjoy and stay with the company.  I am going back in the fall to work towards a Phd with the same professor.  He is a great mentor to me.  A very good chemist and accomplished spectroscopist. 

It would not be as enjoyable if you were an insect, haha.  I wish I had more to do with the actual testing and monitoring.  I just make the compounds and ship them to another facility to be made into lures.

Great read by the way!!  I am having trouble finding time to sit down and finish it, but I am doing few pages here and there. 

Cheers

[discodermolide]

Perhaps you could ask about the biological results of the compounds you make.

[AlphaScent]

You are most likely correct.  I will say that most of my work for the company is done from a published paper.  A lot of the chemical ecologists that publish do have some of the bio assays along with the chemical synthesis.  I guess that is enough to satisfy me most of the time.  Terrible thing to say being a scientist.  Should usurp as mush as possible.

[kriggy]

Simple……We find a compound (sometimes serendipitously such as acetylsalicylic acid…well a derivative anyways), elucidate its structure through our tools such as NMR, IR, and then we think about our toolbox of reactions that make such connectivities possible.  Some are darn near impossible to carry out, as they require biochemicals which are either endogenously produced, or uber expensive for a one gram sample.  Some are not….take the aspirin example listed above.  Simply adding acetic anhydride to salicylic acid yields aspirin.  Hope this helps.
                  -Z

Yeah I kind of realized that. I was more interested in the thinking process. What makes you pick this compound? I know its not simple question and there is a lot of possible answers. I was just hoping that you guys can uncover this area for me because none (OR I dont know anyone who does)at my school does total synthesis and I somehow found that this field is very interesting

[TheUnassuming]

Well I think @Diso gave the two most important ways a lab will choose a target (as far as I have seen).
 
1: You have a shiny new reaction that you want to prove is useful, so you use it to make a natural product that has biological relevance.
2: You are interested in a protein/receptor/biological target that a known natural product can hit, so you want provide an efficient synthetic route to the compound in scale (if its already an good drug: taxol) or so you can make analogues to do SAR. 

There is often a sort of "mount everest" aspect to the natural product chosen as well.

[orgopete]

I had started a reply, but then thought better of it. I'll try again. If you are wealthy, you can do anything you wish. However, if you must spend someone else's money, you should think of how you can appeal to their interests. If you are in an academic environment, you may have some money without strings. If you are seeking grants, they are very competitive. I can't say you wouldn't get funding for a biologically active compound, but I would be doubtful just saying a compound has biological activity would be sufficient. I think you may find the chemical literature will often show several groups working on a hot compound, because of the importance of the biological activity. I suggest that shows biological activity trumps chemistry.

I think you can get funding for chemistry, but this may be more difficult than in an earlier time. You nearly have to have proven your new chemistry works before you get it funded. If you are trying to fund chemistry or a new reaction, there isn't much to fall back on if the reaction fails. If the reason for the research is the chemistry, it's possible the reaction may never work. It is virtually the nature of organic synthesis, there will be a lot of failures to accompany success. There isn't a plan B and funding agencies know this as well. The practical aspect of this is that many principle investigators work on their next project with the funding from their current project. It improves their track record.

Back to the question, I liked working in industry. I liked the idea that I was trying to synthesize something people would pay cold hard cash to get. I preferred working on a hot project, as that probably means it was considered more likely to be commercialized. I also liked that funding was easy and our equipment was good.

[discodermolide]

You might like to read this excellent review by Baran:
Christian A. Kuttruff,a Martin D. Eastgateb and Phil S. Baran
Natural product synthesis in the age of scalability
Natural Product Reports
DOI:10.1039/c3np70090a


[kriggy]

You might like to read this excellent review by Baran:
Christian A. Kuttruff,a Martin D. Eastgateb and Phil S. Baran
Natural product synthesis in the age of scalability
Natural Product Reports
DOI:10.1039/c3np70090a


I will for sure. Thank you all for answers