Publication

Application of Click Chemistry for PET

Mirfeizi, L., Campbell-Verduyn, L., Dierckx, R. A., Feringa, B. & Elsinga, P. H., Oct-2013, In : Current organic chemistry. 17, 19, p. 2108-2118 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

Sharpless et al. presented, in 2001, a review in which they introduced the concept of "click chemistry". In this review a "new way" of making chemicals, with a particular emphasis on drugs, is presented. Current drugs are often based on natural products that were first extracted from plants or other organisms and then with enormous effort were synthetically reproduced by chemists. Sharpless et al. propose to shift the focus away from the structure, which chemists focus on when they synthesize natural products, towards the function of molecules. Rather than making natural products with known biological activity and using these as templates for small modifications, it is proposed to make large libraries of compounds using (mainly) modular chemistry. After all, when looking for new and better drugs, it is the function that matters rather than the structure. This approach mimics nature in that it involves making a great variety of different compounds starting from a relatively small number of building blocks via a set amount of reactions. These sets of reactions have been termed "click reactions" in which simple molecules with specific functionalities can be "clicked" to each other to form a large variety of compounds with relative ease that can subsequently be tested as potential drug candidates. For these "click reactions" Sharpless also looks to nature for inspiration. Ideally, the reaction conditions should be simple, involving no or benign solvents and the reaction itself should be insensitive to oxygen and water.

It was found that copper not only accelerates the reaction but also controls the regioselectivity since in the presence of copper, only the 1,4-isomer is formed. The reaction proceeds in water, with or without co-solvent at room temperature and is relatively fast. The reaction is 100% atom efficient which means that there are no side products so the work up is usually simple. It can take place in a wide pH range which makes is suitable for biological compounds that require a specific pH. Furthermore the azide and alkyne functionalities are bioorthogonal, so theoretically, other functional groups present in a biological environment will not touch them. Finally the triazole product is biologically stable.

Original languageEnglish
Pages (from-to)2108-2118
Number of pages11
JournalCurrent organic chemistry
Volume17
Issue number19
Publication statusPublished - Oct-2013

    Keywords

  • Fluorine-18, Click chemistry, Radiochemistry, PET, POSITRON-EMISSION-TOMOGRAPHY, COPPER-FREE CLICK, 1,3-DIPOLAR CYCLOADDITION, IN-SITU, ESCHERICHIA-COLI, TERMINAL ALKYNES, AZIDES, DESIGN, ACETYLCHOLINESTERASE, INHIBITOR

ID: 5979127