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조회103

서울대학교

Angew. Chem.-Int. Edit., Dec 15 2025, 64 (51) e202518622 | https://doi.org/10.1002/anie.202518622 Modular Synthesis of Pyritide-Inspired Macrocycles Featuring Bipyridine Motifs

Ji Hyae Lee ^{1 †}, Sihyeong Yi^{1 †}, Juhyun Bang¹, Hyun Choi ¹, Seung Bum Park ^{1 *}

¹Department of Chemistry, Seoul National University, Seoul, 08826, South Korea.

^†These authors contributed equally

^*Corresponding author: correspondence to Seung Bum Park

Abstract

Macrocycles represent a promising class of drug-like scaffolds with unique structural features and the ability to engage challenging targets such as protein-protein interactions. Inspired by structural characteristics of pyritides, we constructed a library of 27 diverse macrocycles via a build/couple/pair approach, enabled by efficient synthesis of bipyridine-based triaryl building blocks through azaindole cleavage. Kinetic and cheminformatic analyses confirmed both reactivity trends and structural diversity. From this library, we identified a potential ferroptosis inhibitor, 6paW, with clear structure-activity relationships, validating our diversity-oriented synthesis platform. This strategy offers a robust approach to macrocycle library design, expanding opportunities for targeting previously inaccessible biological space.

논문정보

형식Research article
게재일2025년 12월 (BRIC 등록일 2026-01-07)
연구진국내 연구진
분야 바이오·의료융합 > 다학제 융합/복합

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