The KNCV-Backer Prize is awarded annually to the best PhD thesis in the field of organic chemistry that was defended in the Netherlands. The Committee consisted of Marthe Walvoort (Chair), Tati Fernández-Ibáñez, Bauke Albada and Gert de Cremer; experts in a wide range of disciplines within the organic chemistry field.

In total, 10 theses were submitted this year. They were judged based on the scientific quality, the relevance of the research, the clarity and structure of the thesis and their contributions to the field of organic chemistry. The jury was impressed by the quality of all theses. From the first round in which each thesis was reviewed by two jury members, a sub-set of 3 theses was selected. After extensive deliberations, the jury has decided to award the 2021 KNCV Backer prize to Mira Holzheimer for her PhD-thesis titled ‘On the Total Synthesis of Archaeal and Mycobacterial Natural Products’. The study was conducted at the University of Groningen under the guidance of Prof. Adri Minnaard.

In her thesis, Dr. Holzheimer described the synthesis of all parts of the complex 86-carbon macrocycle crenarchaeol, of three cell wall diacyl trehaloses (DATs), and of the glycolipid pentaacyl trehalose (PAT). Apart from the complexity and elegance of the synthetic approaches that led to these compounds, the jury was also impressed by the original approach and well-written thesis: the storyline in the thesis takes the reader on an inspiring journey of various challenging characters in ‘total synthesis’ in which difficult synthetic steps are interwoven with questions regarding the originally published structure of the ultimate natural product.

Many natural products are of a complexity that challenge our current understanding of chemical reaction pathways, and our ability to reproduce them. The complex organic molecules produced by archaea apparently even challenge our ability to accurately characterize them. Dr. Holzheimer experienced this first hand: only after the initial target compound was prepared, she realized that the published identity of one chiral center was in reality inverted. Nevertheless, she still pursued the synthesis of the full crenarchaeol macrocycle, being exemplary for the perseverance that led to this exceptional piece of work.

The outstanding quality of the synthetic work, the clearly written thesis, the impact the results will have on the verification and identification of natural products, and the clarity of the account of the work, convinced the jury to declare this thesis as the winner of the 2021 KNCV-Backer prize.