可欣
化学
PCSK9
前蛋白转化酶
枯草杆菌素
点击化学
叠氮化物
组合化学
立体化学
乙二醇
分子内力
炔烃
生物化学
有机化学
低密度脂蛋白受体
酶
胆固醇
催化作用
脂蛋白
作者
Jeffrey T. Kuethe,Joshua Lee,David A. Thaisrivongs,Nobuyoshi Yasuda,Scott Pollack,Joseph F. Leone,Jimmy DaSilva,Mirlinda Biba,Fuh‐Rong Tsay,Erik L. Regalado,Ji Qi,Hongming Li,Guilherme Dal Poggetto,Ryan D. Cohen
出处
期刊:Organic Letters
[American Chemical Society]
日期:2023-06-29
卷期号:25 (27): 5001-5005
标识
DOI:10.1021/acs.orglett.3c01635
摘要
The solution-based gram-scale synthesis of complex and highly potent proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitor 1 is presented. Construction of Northern fragment 2, followed by stepwise installation of Eastern 3, Southern 4, and Western 5 fragments, provided macrocyclic precursor 19. This intermediate was cross-linked via an intramolecular azide-alkyne click reaction, which preceded macrolactamization to afford the core framework of compound 1. Finally, coupling with poly(ethylene glycol) side-chain-based 6 gave the PCSK9 inhibitor 1.
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