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. 2025 May 27;31(30):e202500860.
doi: 10.1002/chem.202500860. Epub 2025 Apr 21.

A Sydnonimine-based Click-and-Release Approach to Cyclic Products

Guillaume Force  1 , Minghao Feng  1 , Davide Audisio  1 , Pierre Thuéry  2 , Emmanuelle Schulz  3 , Frédéric Taran  1
Affiliations

A Sydnonimine-based Click-and-Release Approach to Cyclic Products

Guillaume Force et al. Chemistry. .

Abstract

Herein, we report a general, efficient, and practical methodology for the macrocyclization of compounds based on the combination of a Cu-catalyzed click-and-release reaction and a hydrophobic tag. The procedure allows the preparation of cyclic products of different sizes and with various functionalities without the need of purification.

Keywords: click‐and‐release; copper; cycloaddition; macrocycles; sydnonimines.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Click strategies to macrocyclization. CuAAC: Cu‐catalyzed Azide‐Alkyne Cycloaddition; SPAAC: Strained‐Promoted Azide‐Alkyne Cycloaddition; TEC: Thiol‐Ene Click; NCL: Native Chemical Ligation; rGO: reduced Graphene Oxide.
Figure 2
Figure 2
Click‐and‐release strategy to cyclic products. A) Synthesis of pyrene‐containing sydnonimine 5. B) Intermolecular click‐and‐release reaction of sydnonimine 4 with model alkyne 6. C) Intramolecular click‐and‐release reaction of compound S9, purification procedure of cyclic pyrazole products. LC/MS profiles refer to reaction crude analysis after 2 hours before (top) and after (bottom) rGO work‐up. BPDS: bathophenanthroline disulfonate.
Figure 3
Figure 3
Scope of the reaction. Influence of the size. Reactions were conducted at 35 mM of substrates S1–8 in DMSO/H2O (1:1). Cyclization's were conducted at 37 °C except for CyP7 which was conducted at 50 °C.
Figure 4
Figure 4
Scope of the reaction. Preparation of cyclic peptides. Reactions were conducted at 35 mM of substrates S9–13 in DMSO/H2O (1:1). Cyclization's were conducted at 50 °C except for CyP9 which was conducted at 37 °C.
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