Dr. Florencio Zaragoza, organic chemist at Lonza AG, Visp, Switzerland, talks to Dr. Vera Köster for ChemistryViews.org about his experiences in the chemical and pharmaceutical industry, chemical troubleshooting, and the importance that employees should take ownership of a project.
Tell us a bit about how your career has developed, please.
After finishing high school at the German School in Valencia, Spain, I studied chemistry at the Georg-August University of Göttingen, Germany. I fell in love with organic chemistry, especially during my final year project in the group of Günter von Kiedrowski dealing with the synthesis of polyamine carbodiimdes. Then I did my PhD work in the group of Michel Franck-Neumann in Strasbourg on the use of carbenes in natural product synthesis. I consider the multistep synthesis of complex target molecules as the best training for young chemists, because it requires retrosynthetic thinking and the knowledge of many types of reaction and their limitations.
Then I spent one post-doctoral year at the University of Basel, Switzerland, in the group of Andreas Pfaltz and one year in the group of Alan P. Marchand at the University of North Texas, Denton, USA. During this year I really learned how to prepare and purify organic compounds which training has been of great value to me.
I commenced independent research at the Technical University of Dresden in 1993, under the guidance of H. U. Reissig. However, teaching and academic life was not what I really enjoyed, so in 1994 I started to work at Novo Nordisk in Maaloev, Denmark, as medicinal chemist.
My first job in industry was a pleasant surprise: all employees were empowered and the working environment was highly collegial. I spent 13 years there, working on various medicinal chemistry projects and on the development of solid-phase methodology for parallel synthesis. Unfortunately, from 2003 to 2007 Novo Nordisk slowly withdrew from small-molecule drug development, and I, therefore, decided to switch company. Since 2007 I have been working at Lonza, Visp, Switzerland, a company mainly focussed on custom manufacturing and the production of food additives, disinfectants, and other specialities.
What do you do in your current position?
My department supports the sales people with the assessment of customer enquiries, mostly related to the production of agrochemicals. In my team, we also determine if a compound can be prepared at our site in Visp, and how much it will cost. I am in charge of one technician and a laboratory, where we test new ideas and prepare samples for our customers.
What does that mean in more detail?
I spend most of my time with retrosynthetic analyses, route scouting, synthesis development, and chemistry troubleshooting. It’s great fun.
What other skills do you need?
Chemists at Lonza must know about safety regulations and the limitations and capabilities of our equipment in Visp. However, this is something you can learn on the job.
Most personnel departments consider social skills as a critical selection measure. However, I think most people will only deliver a star performance when they own their project and are going to benefit individually from any success. I think most modern companies understand this, and young chemists shouldn’t be afraid of losing their individuality or freedom to make decisions when joining a company.
I consider it important that everybody who supervises others makes sure that his employees clearly know about the background and potential impact of their projects, and empowers them as much as possible, so that the employees take ownership of the project. People’s ability and willingness to do this varies a lot.
What problems or decisions do you deal with regularly?
Usually, I wrestle with two types of problems: identify the most cost efficient preparation of some target compound – these are mostly customer enquiries –, and get some difficult reaction to work properly. These problems never get solved definitely, because new reactions are being developed all the time, which may give a cheaper access to some of our products. And you never really finish optimizing a reaction. So, I have to decide how much time to spend with each problem. This can be tricky, because a number of non-chemical aspects must be considered, too, such as the potential business size, the strategic importance for Lonza, and the availability of other, competing projects.
What do you enjoy most about your job?
I have always enjoyed retrosynthetic analysis and chemical troubleshooting. When performing organic synthesis on a large scale – we have several 12 m3 reactors here – the most amazing things can happen. Upon upscaling, reactions that work well in the lab often cause unforeseen problems, and the weirdest byproducts can sometimes be isolated. I find it is fascinating to figure out what these byproducts or problems are, and how to avoid them.
I find it particularly rewarding to identify products resulting from mechanistically new reactions. When interpreting spectra, chemists are highly biased toward the expected product, and toward known reactions. To elucidate the structure of products formed by unknown or unexpected mechanisms is, therefore, quite difficult.
Important projects can stay in my laboratory for more than a year, what allows us to optimize syntheses thoroughly. When working on one synthesis for so long, all conceivable strategies and shortcuts can be tested, and often a short, cheap, and patentable synthesis can be found, what is very gratifying. One instance of such work recently resulted in a practical synthesis of medetomidine (WO 2013011157 A1).
Why did you decide to move from academia to this job?
During my time at the Technical University of Dresden I noticed that instead of organizing courses and teaching, I prefer to struggle on my own with some chemistry in the lab. I am too much interested in specific problem solving and in broadening and deepening my own knowledge in chemistry.
At Lonza, chemists have the possibility to add a lot of value with their work, and a solid knowledge of chemistry is appreciated by everyone. Both at Novo Nordisk and at Lonza chemists work on highly relevant projects, what gives true job satisfaction. At the university, I often felt like developing solutions for fictional problems.
In industry, chemists also have to collaborate with professionals of other disciplines, and have thus the opportunity to learn about other subjects. Medicinal chemists, for instance, must learn about pharmacokinetics, biochemical assays, metabolism, toxicology, etc. I always enjoy learning new things.
What was most challenging in your job?
Let me start with the famous quote of J. M. Keynes: ‘The difficulty lies not so much in developing new ideas as in escaping from old ones’.
When I look back, some of the most costly mistakes I made were caused by my fixation on some prejudice or dogma, and my unwillingness to challenge this idea. For instance, medicinal chemists often are convinced that their target requires a certain pharmacophore which cannot be modified. Or chemists are convinced that a certain reaction cannot work because a required transition state is too energy-rich. Such prejudices can sometimes cost more than a year of futile efforts. So, I consider it important to make unreasonable experiments from time to time, and to regularly challenge established routines, strategies, and mechanistic notions.
What advice would you give to students pursuing a job in this area?
I would encourage young chemists with an interest in biochemistry and biology to pursue a career as medicinal chemist in the pharmaceutical industry. The discovery of new small-molecule drugs is a fascinating area of research. Creativity and a willingness to learn about non-chemical disciplines are essential.
The main disadvantages of medicinal chemistry are that it is frustrating most of the time – but chemists should be frustration-resistant, anyway –, and that nobody at pharmaceutical companies really cares for beautiful chemistry. Drug discovery is all about the biological properties of a compound, not its structure or synthesis.
Jobs with a stronger focus on chemistry include chemical research and process development at pharmaceutical, agrochemical, or other companies. Here a chemist will have to learn about chemical engineering, process safety, and the many limitations of large-scale chemistry.
Some companies offer summer jobs, which allow students to become more familiar with the chemical industry. I would strongly recommend these to everybody, also to those who want to stay in academia. Before starting at Novo Nordisk, I had a lot of unwarranted prejudices against ‘industry’.
We are confronted with huge unmet medical needs, huge environmental problems, and do not really understand what we are, i.e. how conciousness works. I am convinced that the greatest technological breakthroughs are to occur in the future. A job as chemist is not just the application of old rules of the craft to new problems, but still an intriguing expedition into the unknown.
Thank you for the interview.
Florencio Zaragoza Dörwald studied chemistry at the Georg-August University, Göttingen, Germany, and Université Louis Pasteur, Strasbourg, France, where he obtained his Ph.D. in 1990 on the synthesis of natural products under the guidance of M. Franck-Neumann and M. Miesch.
He spent one postdoctoral year in the group of A. Pfaltz, University of Basel, Switzerland, and one in the group of A. P. Marchand, University of North Texas, Denton, TX, USA. Till 1994, Zaragoza worked on the synthesis of unnatural amino acids at the Technical University of Dresden, Germany. Till 2007, he had a position as a medicinal chemist at Novo Nordisk A/S, Maaloev, Denmark.
Currently, Zaragoza Dörwald is employed as organic chemist at Lonza AG, Visp, Switzerland.
- Direct C4 arylation of crotonaldehyde with arenediazonium tetrafluoroborates,
Florencio Zaragoza, V. Heinze,
Tetrahedron Lett. 2011, 52, 4678–4680.
- One-pot diazotization and Heck reaction of methyl anthranilate: 2-(3-oxopropyl)benzoic acid methyl ester,
Org. Syn. 2010, 87, 226−230.
- 2-(4-Alkylpiperazin-1-yl)quinolines as a new class of imidazole-free histamine H3 receptor antagonists,
Florencio Zaragoza, H. Stephensen, B. Peschke, K. Rimvall,
J. Med. Chem. 2005, 48, 306–311.
- One-step conversion of alcohols into nitriles with simultaneous two-carbon chain elongation. (Cyanomethyl)trimethylphosphonium iodide as a reagent with a dual mode of action,
J. Org. Chem. 2002, 67, 4963–4964.
- (Cyanomethyl)trialkylphosphonium iodides; efficient reagents for the intermolecular alkylation of amines with alcohols,
Florencio Zaragoza, H. Stephensen,
J. Org. Chem. 2001, 66, 2518–2521.
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