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Synthesis 2023; 55(11): 1613-1615
DOI: 10.1055/s-0040-1720068
editorial

SYNTHESIS Special Issue in Honor of Professor Cristina Nevado

Margaret M. Faul∗
a   Process Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
,
Corinna S. Schindler∗
b   Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
,
Alois Fürstner∗
c   Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany
› Author Affiliations
› Further Information
 
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It is a privilege and honor to congratulate Professor Cristina­ Nevado on receiving the 2021 Dr. Margaret Faul Women in Chemistry Award. This award, sponsored by Thieme Chemistry and Science of Synthesis (https://science-of-synthesis-thieme-com.accesdistant.sorbonne-universite.fr), recognizes outstanding achievements of young female organic chemists of any nationality within the first 15 years of their independent career. The first recipient was Professor Sarah Reisman (2019) from the California Institute of Technology, USA. In addition to being leaders in science, the awardees are also acknowledged as role models that inspire the next generation of young women in science to consider careers in chemistry, be it in industry or academia.

When the Women in Chemistry (WIC) Award was initiated in 2019, it was the first prize of its kind; it nicely complements the Thieme-IUPAC Prize established back in 1992, sponsored by the same publishing house. These awards reflect Thieme’s long-term policy of promoting excellence in science at large. Each WIC awardee is also honored by a special issue of SYNTHESIS. The 17 dedicated articles comprising this issue bear witness to the appreciation of her peers for the work of Professor Nevado. To pay her this tribute is even more warranted since the actual award ceremony and lecture had to be held virtually, rather than in person, in July 2021 because of the then rampant COVID-19 pandemic.

Cristina Nevado graduated with a degree in chemistry in 2000 from the Autónoma University, Madrid, Spain, and received her Ph.D. from the same university in 2004 under the supervision of Professor Antonio M. Echavarren. It was there that her profound interest in π-acid catalysis was kindled, which was no more than a curiosity at the turn of the millennium but has since become textbook knowledge.[1] [2] Next, she joined the group of one of us (A.F.) at the Max-Planck-Institut für Kohlenforschung in Mülheim an der Ruhr, Germany, as a postdoctoral associate. With the intention to expand her knowledge base, she opted for target-oriented synthesis. Without her creativity, dedication, and stamina, it would not have been possible to accomplish the first total synthesis of iejimalide, a marine natural product of remarkable potency yet exceptional sensitivity. This first conquest was rapidly followed by a second-generation approach and a systematic molecular editing exercise, as well as by a detailed assessment of the biological activity and mode of action of this polyene macrolide, for which Cristina’s contributions were also instrumental.[3] A much improved protocol for Stille–Migita cross-coupling of particularly sensitive compounds was a rewarding methodological spin-off, which now enjoys quite some popularity.[4] In Madrid­ and in Mülheim, Cristina also became acquainted with the use of computational tools, both hands-on and in collaboration with experts in the field.

In 2007 Cristina started her independent career as an assistant professor at the University of Zürich, Switzerland, where she was promoted to the rank of full professor in 2013. From the very beginning, she pursued a multidimensional approach, merging method development and computational studies into transition-metal catalysis with target-oriented synthesis and in silico drug design. Gold catalysis has been a major focus of her research program, with the homologous Rautenstrauch rearrangement published as early as 2008 forming an impressive start.[5] The notion that a gold center is capable of stabilizing ‘non-classical’ carbocations generated upon opening of substituted cyclopropanes served as an efficient platform for the stereocontrolled synthesis of various ring systems. The method was scrutinized by a formal enantioselective synthesis of the marine terpenoids of the frondosin family.[6]

This and related projects based on Au+ as a carbophilic Lewis acid catalyst were complemented by forays into the then much more exotic organic chemistry of Au3+. Although Au+, for its ‘noble’ character, was commonly considered to be essentially non-oxidizable under conditions that a functionalized substrate would withstand, Cristina and her team showed that the use of hypervalent iodine reagents cleanly generated such Au3+ species. Their pronounced bias to fall back to the Au+ oxidation state can then be leveraged as an exquisite driving force for the formation of challenging C–C or C–X bonds. Gold-catalyzed ethynylations of arenes engaging weakly nucleophilic acetylides were an early illustration of this concept.[7] In parallel, her laboratory pursued an alternative approach to Au3+ catalysis based on the transmetalation of boronic acid derivatives.[8] Moreover, the Nevado lab managed to isolate and characterize a number of pertinent Au3+ complexes – including some quite spectacular Au3+ carboxylates[9] – and studied their photophysical properties as well as their reactivity vis-à-vis a set of representative coupling partners.

The 1,2-difunctionalization of alkenes and alkynes is another central theme of Cristina’s methodological work. While it comes in various formats, it is arguably most prominent in her work on nickel-catalyzed relayed reductive coupling reactions passing through highly synchronized radical manifolds.[10] These transformations are distinguished by a notable functional group tolerance as well as regio- and stereocontrol; highly enantioselective versions have since been devised.[11] A more recent addition to the list of difunctionalizations developed by the Nevado group is a spectacular asymmetric sulfinyl–Smiles rearrangement driven by visible-light photoredox catalysis, which allows all-carbon quaternary centers alpha to an amide to be generated with excellent optical purity.[12]

Although this editorial is necessarily selective, Cristina’s complementary program in medicinal chemistry and natural product synthesis deserves a mention. In addition to the frondosins referred to earlier, reference is made to her work on the macrolides of the iriomoteolide family. This project is representative in that it spans from the actual total synthesis of these intricate targets and their non-natural analogues to their use as chemical tools that allow the dynamics of the actin cytoskeleton to be studied.[13]

Equally impressive is her work in the area of medicinal chemistry, with special emphasis on tyrosine kinase and bromodomain inhibitors; the latter protein modules recognize acetylated lysine residues, which, in turn, constitute important post-translational modifications of histone proteins involved in transcription and regulation of the chromatin structure. Together with her long-term collaborators, Cristina’s laboratory identified several low micromolar to nanomolar inhibitors of these protein targets by virtual screening campaigns, computational hit-to-lead optimization, chemical synthesis, and subsequent in vitro and in vivo validation.[14]

Cristina is an exigent teacher and excellent mentor for her co-workers; several of them have already started own academic careers. The high number of female students and postdocs during her time in Zürich clearly proves that she is also a successful advocate for women in chemistry. On top of her scientific agenda, she is an active citizen of the scientific community, both at the local and the international level. Specifically, she took much responsibility for the relocation of her department to the brand-new chemistry building of the University of Zürich. She is a member of the standing committee that does all the hard work behind the scenes of the famous annual Bürgenstock Conference. Moreover, she was Senior Associate Editor for ACS Central Science and served on the Editorial Board for Organic Synthesis; she is a current member of the Editorial Board of Science­ of Synthesis.

In recognition of her accomplishments, Professor Nevado has received many awards, including an ERC Junior Investigator Grant (2012), the prestigious Werner Prize of the Swiss Chemical Society (2013), the RSC Award in Organometallic Chemistry (2019), and the Excellence Research Trajectory Award of the Royal Spanish Chemical Society (2020). Thieme Chemistry and Science of Synthesis are proud that this list is now complemented by the 2021 Dr. Margaret Faul Women in Chemistry Award.

As a final note, we would like to mention that the third recipient of the Dr. Margaret Faul Women in Chemistry Award has recently been announced. The prize goes to Professor Michelle Chang, University of California, Berkeley, USA, in recognition of her outstanding work leveraging natural product biosynthesis for the development of new synthetic methods for C–H fluorination and related halogenation reactions, as well as on the production of fuels and chemicals from bio-derived renewable resources using sustainable biocatalysis. The award will be presented to Professor Chang at the European Symposium on Organic Chemistry (ESOC) in Ghent, Belgium, on July 11, 2023.


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Conflict of Interest

The authors declare no conflict of interest.


Publication History

Received: 25 April 2023

Accepted after revision: 25 April 2023

Article published online:
10 May 2023

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