Abstract
Cyclobutanes have attracted significant interest in medicinal chemistry because of their unique structure and potential advantages in pharmacological properties. Nevertheless, 1,2-disubstituted cyclobutanes remain underrepresented, both in the general chemical space and in fragment-based drug discovery libraries. In this study, a two-diversification-point library of cyclobutanesulfonamides was synthesized through a hyperbaric [2+2] cycloaddition reaction between ethenesulfonyl fluoride and tert-butyl vinyl ether as the key step. The sulfonyl fluoride was subsequently transformed into various sulfonamides, whereas the tert-butyl ether was converted into carbamates and triazoles to synthesize a fragment library. Overall, this synthesis contributes to addressing the underrepresentation of 1,2-disubstituted cyclobutane fragments, making a valuable addition to the field of fragment-based drug discovery.
Original language | English |
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Article number | e202400797 |
Pages (from-to) | 1-7 |
Number of pages | 8 |
Journal | European Journal of Organic Chemistry |
Volume | 27 |
Issue number | 45 |
Early online date | 29 Oct 2024 |
DOIs | |
Publication status | Published - 2 Dec 2024 |
Bibliographical note
This article also appears in: Board Members Society Volumes: The Netherlands.Publisher Copyright:
© 2024 The Authors. European Journal of Organic Chemistry published by Wiley-VCH GmbH.
Funding
We acknowledge funding from the Dutch Research Council (NWO) under Applied and Engineering Sciences Grant 18019 (Ready for growth: a new generation of highly versatile fragment libraries). We thank dr. Paul Tinnemans (Solid State Chemistry, Institute for Molecules and Materials, Radboud University) for elucidating the X-ray crystal structures. We acknowledge funding from the Dutch Research Council (NWO) under Applied and Engineering Sciences Grant 18019 (Ready for growth: a new generation of highly versatile fragment libraries). We thank dr. Paul Tinnemans (Solid State Chemistry, Institute for Molecules and Materials, Radboud University) for elucidating the X\u2010ray crystal structures.
Funders | Funder number |
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Radboud Universitair Medisch Centrum | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 18019 |
Keywords
- Cyclobutanes
- Ethenesulfonyl fluoride
- Fragment library
- High-pressure chemistry
- Hyperbaric [2+2] cycloaddition