MICROREVIEW DOI: 10.1002/ejoc.200600837 Aziridines in Parallel- and Solid-Phase Synthesis Christian A. Olsen,* [a] Henrik Franzyk, [a] and Jerzy W. Jaroszewski [a] Keywords: Aziridines / Nucleophilic ring-opening / Solid-phase synthesis / Parallel synthesis / Multi-component reactions Aziridines are versatile and powerful building blocks in or- ganic synthesis due to their high reactivity as well as stereo- and regioselectivity of their ring-opening reactions with nu- cleophiles. Thus, aziridines possess potential as building blocks in the preparation of combinatorial libraries for bio- logical high-throughput screening. Although the develop- Introduction The nucleophilic ring-opening of aziridines with a wide range of nucleophiles is an extremely efficient transforma- [a] Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, 2100 Copenhagen, Denmark Fax: +45-3530-6041 E-mail: cao@dfuni.dk Christian Adam Olsen was born in Copenhagen, Denmark, in 1974. He received a M.Sc. degree in chemical engineering at the Danish Technical University in 2000 with Inge Lundt, after which he spent six months as a research associate at Novozymes A/S in Denmark. He received his Ph.D. degree at The Danish University of Pharmaceutical Sciences in 2004 with Henrik Franzyk and J . W. Jaroszewski as thesis advisors. Part of the Ph.D. Thesis work was conducted in the laboratory of F. Albericio and M. Álvarez in Barcelona, Spain. He currently holds anassistant professorship funded by a Talent Project Grant fromthe Danish Technical Research Council. His research interests include development of synthetic methodology for solid-phase synthesis, preparation and biological evaluation of libraries of neuroactive polyamine toxins, and diversity-oriented synthesis of polyfunctionalized amino acid scaffolds. Recently, he has also initiated a research project concerning the development of novel peptidomimetic oligomers with biological activity. Henrik Franzyk was born in Køge, Denmark, in 1966. He received his M.Sc. (chemical engineering) and the Ph.D. (natural products chemistry) degrees at the Danish Technical University (with S. Rosendal Jensen) in 1991 and 1993, respectively. Following employments as a researcher at Fef Chemicals (1993), post-doctoral positions at Carlsberg Labo- ratory (1994–1996), the Danish Technical University (1996–1997), and Colorado State University (1997, with Frank R. Stermitz), he became a research associate professor at the DanishTechnical University (1998–2000) and then associ- ate professor at The Danish University of Pharmaceutical Sciences (2000). Previous work includes structure elucidation of natural products, biosynthetic investigations, synthetic carbohydrate and glycopeptide chemistry, and semi-synthesis of alkaloids and nucleoside analogues from natural products. Current research interests are focused on the medicinal chemis- try of polyamine toxins as well as on development of solid-phase methodologies for diversity-oriented synthesis. Jerzy W. Jaroszewski was born in Lodz, Poland, in 1950. He received his M.Sc. degree and the Ph.D. degree (with Martin G. Ettlinger) from the University of Copenhagen in 1977 and 1980, respectively. Following employments in post- doctoral position at the University of Copenhagen (1980), research assistant- and associate professorships at the Royal Danish School of Pharmacy (1981–1988 and 1991–1996), visiting fellowship at National Cancer Institute, NIH, Be- thesda, MD (1988–1990, with Jack S. Cohen), and visiting professorships at the Georgetown University Medical School, Washington DC (1991, 1993, 1994), he became full professor at The Danish University of Pharmaceutical Sciences (then the Royal Danish School of Pharmacy) in 1997. Previous work includes biomimetic synthetic chemistry and aromatic ring cleavage reactions, physical organic chemistry, DNA modifications for anti-sense applications, and structure elucidation of natural products. Current research interests focus on isolation and synthesis of biologically active natural products, structure-activity relationships, and applications of NMR spectroscopy. Eur. J. Org. Chem. 2007, 1717–1724 © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1717 ment of strategies for parallel synthesis and solid-phase chemistry utilizing aziridines is still in its infancy, the diverse applications described so far emphasize their utility. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) tion in organic synthesis. [1] Alongside analogous three- membered heterocyclic electrophiles, including epoxides, cy- clic sulfates, episulfonium ions, and aziridinium ions, azirid- ines have been highlighted as important “click” chemistry reactants/tools in the original account on this subject by Sharpless and co-workers. [2] Aziridine chemistry has indeed been extensively exploited by organic synthetic chemists. In the last several decades, more than 200 research papers have been registered in the Chemical Abstracts database every