Radical cascade cyclization of amino acid-tethered 1,6-enynones with sulfonyl hydrazides for N-terminal modification: synthesis of functionalized succinimide derivatives

Sivanantham, MathiyazhaganJacob Stanley, JenisMuthu, KesavanVelmathi, SivanSenadi, Gopal ChandruSenadi, Gopal ChandruRamasamy, Mohankumar2026-08-232026-08-232025-08-0120462069https://doi.org/10.1039/d5ra04754dhttp://nitt.ndl.gov.in/handle/123456789/229A metal-free strategy for the N-terminal cyclization of amino acids has been developed by synthesizing highly functionalized succinimide derivatives through radical cyclization of amino acid-tethered 1,6-enynones with sulfonyl hydrazide using NIS and H2O2 as an oxidant. The notable advantages of this work includes time-efficient, good E/Z ratio, moderate to good yields, and was synthesized on a gram-scale. Furthermore, the synthetic utility of the product 5aa was performed by (i) Suzuki coupling reaction with iodo-functionality; and (ii) dipeptide formation using glycine methyl ester. © 2025 The Royal Society of Chemistry.enRadical cascade cyclization of amino acid-tethered 1,6-enynones with sulfonyl hydrazides for N-terminal modification: synthesis of functionalized succinimide derivativesArticle