Here comes some stories!

Having decided back in 1977 to pursue a PhD degree in Organic Chemistry, I soon realized that I needed much more knowledge in the domain of Organic Synthesis than I had accumulated during my undergraduate years. I remember to fall in love with this branch of Chemical Sciences after reading (and understanding!) the books by H. O. House, “Modern Synthetic Reactions”, Ian Fleming´s “Selected Organic Syntheses. A Guidebook for Organic Chemists” and “Frontier Orbitals and Organic Chemical Reactions”, Bindra& Bindra´s, “Creativity in Organic Synthesis”, Morrison& Mosher´s, “Asymmetric Organic Reactions”, S. Warren´s “Organic Synthesis: The Disconnection Approach” and many others. I was hooked to Organic Synthesis as it combined the art of transformation and understanding which seemed to me to be key for a life journey. I became addicted to books and in one of my incursions to a secondhand bookstore I had the good fortune to find the historical edition of “Perspectives in Organic Chemistry”, edited by Lord Todd in honor of Sir Robert Robinson´s 70th birthday (and for a bargain...).

 

In Organic Synthesis, success usually goes hand to hand with hard work and focus as one has to master its knowledge and practice at the highest level possible. I was introduced to research under the guidance of Professor Albert J. Kascheres who investigated the reactivity of small ring compounds (cyclopropenones and cyclopropenimines). I was taught by AJK the rigour of analysis and mechanistic thinking in order to unravel the structures of the heterocycles formed in the cycloaddition reactions of these strained 3-membered ring compounds with nitrogen ylides. I also acknowledge the contribution of Professor Edmundo A. Rúveda during these years who disclosed to me the beauty of natural products total synthesis.

 

At that point, the work of R. B. Woodward and E. J. Corey had captured my imagination and I was decided to look for a postdoctoral position in the stereocontrolled total synthesis of natural products. I was lucky enough to be admitted to Clayton H. Heatcock´s group at University of California, Berkeley where I stood from 1982-84. I was exposed to my first great professional challenge: to keep track with all the exciting Chemistry underway in CHH´s group and contribute to the research I was assigned to which targeted the total synthesis of erythronolide A based on the acyclic stereocontrolled methodology developed there. Out of many lessons learned during those years, one remained vividly in my mind: CHH´s passion to teach and to motivate students.

 

Upon my return to the University of Campinas (UNICAMP) I started my independent research in 1985, focusing on the synthesis of some insect pheromones based on stereoselective aldol methodologies developed by Heathcock and others. I was also inspired by the beauty of the CHH work on Daphniphyllum alkaloids when I decided to incorporate the chemistry of N-acyliminium ions as one of my research topics in the early 90´s.

 

The sheer emotion of observing insects landing at lab bench upon completion of the total synthesis of the sex pheromone of L. serricorne (even before taking a NMR spectrum!), isolating an alkaloid via a tandem process, reproducing in the laboratory the structure of the antibiotic 10-deoxymethynolide or contributing to the elucidation/stereochemical revision of natural products such as delactonmycin and the coibacins A and B is a tribute to a branch of the Chemical Sciences which has offered a lot to make life better.

 

Here come some concerns.

 

Since I started studying Organic Chemistry several key reactions and catalysts entered the scene and have transformed the way we design and carry out the construction of molecules in the lab: Sharpless asymmetric epoxidation and dihydroxylation, Noyori and Knowles asymmetric hydrogenation, Corey-Bakshi-Shibata asymmetric reduction, Evans’s chiral auxiliaries, Tsuji-Trost asymmetric alkylation, Mukayama’s catalytic asymmetric aldol reaction, Heck/Suzuki/Negishi coupling reactions, and many others. Not only the toolbox available for synthetic chemists has expanded significantly but also the rationale planning of the synthetic endeavour has impacted the area. The heuristic principles of the retrosynthetic analysis combined with wisely applied biogenetic/biosynthetic reasoning’s led to some of the masterpieces in total synthesis of natural products as Heathcock’s Daphnphyllum alkaloids syntheses.

Despite all the achievements in the total synthesis of natural products in the academic settings and the valuable training that it provides to its practioners, there are still major issues to be solved in order to translate its academic achievements to society. As pointed out by professor P. Baran, while so far only 30 mg of taxol has being delivered by total syntheses, currently the industrial output through plant cell technology is in the ton scale. Brevity, efficiency, scalability, and environmental impact are issues that have to be addressed in order to secure for Organic Synthesis a future as brilliant in the coming years as we have seen over the last decades. This is regardless of area in which one will be engaged: total synthesis, methodology, catalysis, etc…

A final word is in order to address some current practices in our area. It is time to rethink some of the values that have prevailed among us on concerning the hype on the quantitative aspects of the scientific output. The metrics that have being adopted by funding agencies and significant part of our community are not to be kept if we really want to see advances in our field. Not only increased scientific production is not correlated to increase of scientific knowledge but it promotes some bad practices among us such as irreproducible results, inflation of the scientific achievements (qualifications such as “novel”, “extraordinary”, “marvelous”, and so forth) and proliferation of co-authorship without due contribution to the work. These are some practices that undermine the ability of scientists to discriminate the most relevant problems awaiting to be studied from the well addressed ones (to see the forest for the trees).

A final comment goes to the widespread careless description of experimental results which prevents them to be reproduced and sometimes goes hand to hand with erroneous results. The current practice of several publications to publish experimental details as supporting information depreciates the fact that reproducibility remains the essence of Science, as pointed out by Hudlicky and Reed in The Way of Synthesis (Wiley VCH, 2007), not to say about fraudulent results which undermine the central tenet of Science which is confidence and search for the truth. Unethical behaviour should be vigorously rejected and senior scientists have an obligation to instill strong ethical and moral values in their progeny, as stated recently in an editorial signed by professors Noyori and Richmond (Ethical Conduct in Chemical Research and Publishing) published in Adv. Synth. Catal. 2013, 355, 3-9.

The Brazilian Academy of Science (ABC) has issued guidelines on responsilbe scientific practices  which is worth reading and implementing (if not, already in place). Check out here.

FAPESP (São Paulo Funding Agency) has also disclosed its code of good scientific practice. Check it out here.

 

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A DETAILED LIST OF PUBLICATIONS FROM MY LABORATORY CAN BE FOUND HERE