Related Experiment Video
Updated: Sep 19, 2025

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Macrocyclization of Unprotected Peptides via Cycloaddition between o-Diones and Furan-2(3H)-one
Shuaishuai Sun1,2, Jun Chen1, Sen Jiang1
1State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.
Abstract:
Cyclic peptides have emerged as powerful modulators of biomolecular interactions, driving the need for efficient macrocyclization strategies to construct diverse libraries from unprotected peptides. Herein, we present an efficient method for the macrocyclization of unprotected peptides, utilizing a cycloaddition reaction between 9,10-phenanthrenequinones and furan-2(3H)-one derivatives. This method proceeds under mild, neutral aqueous conditions with fast kinetics and demonstrates broad compatibility with peptides containing functional amino acids by generating cyclic peptides with PD-L1 targeting and cell-penetrating activities.
Related Concept Videos
Cycloaddition Reactions: Overview
Cycloaddition Reactions: MO Requirements for Thermal Activation
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Preparation of Epoxides
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of...

