Learn from Nature and make it Even Better

Stefano Biondi , Italy

Learn from Nature and make it Even Better The possibility to do things in a better way or produce something useful using innovative approaches is very exciting. Solving problems is a difficult challenge, a learning process, and a reward when successfully achieved.

I am a chemist by training and an innovation seeker by passion, with more than 20 years of professional experience in Pharma and Biotech as medicinal and pharmaceutical chemist. Member of the management team of Valevia Pharmaceuticals GmbH, a privately owned biopharmaceutical company focused on the development of novel therapies against resistant pathogens in infectious diseases. Founder of Innovative Solution a medicinal and pharmaceutical chemistry consultancy company. Inventor of over 30 patents, including Anti-infectives, CNS, Cardiovascular, Ophthalmic and Anti inflammatory drugs.

If I look back and remember all the exciting discoveries and inventions that I have contributed to it is quite difficult to choose just one which is the best. All of them are filled with emotions, feelings, and a feeling of satisfaction and pride at having been able to put my knowledge to good use.

On several occasions I have been part of international research and development teams engaged in challenging projects aiming at the identification of the drugs of the future.

During my career as a medicinal and pharmaceutical chemist I have contributed to the identification of several new drug candidates that have entered into clinical trials in various therapeutic areas (anti-infectives, psychiatry, cardiovascular disease, pain, inflammation, ophthalmology, metabolic diseases).

Among them, I have identified a salt with superior solubility as an antipsychotic drug candidate, I have improved the bioavailability of drug candidates using suitable prodrugs, I have modified the pharmacological activity of several classes of compounds including preparing selective phosphodiesterase inhibitors building on the benzodiazepine core structure but not the activity, I have switched the selectivity of a squalene synthetase inhibitor (Squalestatin) for use against the fungal enzyme rather than the human enzyme, to mention only a few examples.

But the invention that I would like to highlight specifically is in the field of synthetic and medicinal chemistry and is related to my work on betalactam antibiotics. At the time, we were working on a fascinating new class of betalactams, closely related to carbapenems, that we called trinems, (the tricyclic carbapenems).

At that time Sanfetrinem, a broad spectrum betalactam antibiotic was in clinical development for community acquired infections, but its synthesis was too long, too expensive, and combined with a low yield. We were given a task of (a) improving the synthesis yield from 5 to 20%, and (b) reducing the number of synthesis steps from 14 to less than 10.

We set up a task force to solve the problem and after several attempts I was able to identify a shortcut that could reduce the total number of steps to 8. Initially I used a reagent that achieved a 50% yield and a side product that had never been seen before.

I still remember the discussions with the analytical chemistry specialists that proposed a structure that had never been observed before and went against all the literature on the subject. X-ray analysis of the compound revealed that the experts were right and opened an entirely new avenue for product synthesis. This observation revealed that boron could achieve something unique, not feasible using other reagents, and this could enable us to completely control the stereochemistry of trinems and prepare all 32 stereoisomers.

The fascinating part of the story lay in the fact that the source of chirality was provided by -pinene, a natural product produced by pine tree. The research progressed further, focusing on the reasons for the selectivity. I designed a new ligand derived from 2-methyl cyclohexene that provided even better results. It is a great experience to learn from nature and make it even better.

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