Total Synthesis of Enlicitide Decanoate

IF 14.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of the American Chemical Society Pub Date : 2025-03-24 DOI:10.1021/jacs.4c15966

Hongming Li, David A. Thaisrivongs, Gao Shang, Yonggang Chen, Qinghao Chen, Lushi Tan, Kai-Jiong Xiao, Reed T. Larson, Jeffrey T. Kuethe, Joshua Lee, Nicholas R. Deprez, Andrew F. Nolting, Marc Poirier, Paul G. Bulger, Erik L. Regalado, Mirlinda Biba, Fuh-Rong Tsay, Jimmy DaSilva, Chris K. Prier, Christopher A. Strulson, Kerstin Zawatzky, Zhu Liu, Justin A. Newman, Kathleen Sokolowsky, Weijuan Tang, Kari Hullen, Nimisha Thakur, Cody Welch, Smit Patel, Yu He, Jing Xu, Narayan Variankaval, Artis Klapars, Jongrock Kong, Richard Desmond, Richard Varsolona, Peter E. Maligres, Carlos A. Pons Siepermann, Lee Robison, Tiffany Piou, Clara Hartmanshenn, Anagha Chandra, Anisha Patel, Marc R. Becker, Guiquan Liu, Jianjun Duan, Baoqiang Wan, Chengqian Xiao, Yongpeng Yuan, Xiaohui Cao, Lu Chen, Ruxia Yi, Zheng Wu, Minyi Feng, Donghong Li, Zhiyan Song, Yawei Dong, Julin Sun, Biao Li, Guangxin Shao, Louis-Charles Campeau, Jingjun Yin

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Abstract

We report the total synthesis of enlicitide decanoate, an orally bioavailable inhibitor of proprotein convertase subtilisin/kexin type 9 that is being developed for the treatment of atherosclerotic cardiovascular disease. It is a highly complex macrocyclic peptide with a significant number of nonpeptide structural elements that presents a daunting synthetic chemistry challenge. We describe the development of a convergent, efficient, and robust manufacturing process that enables the large-scale production of enlicitide.

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烯酸酯的全合成

我们报道了enlicicitide decanoate的全合成，enlicicitide decanoate是一种口服生物可利用的蛋白转化酶subtilisin/ keexin 9型抑制剂，正在开发用于治疗动脉粥样硬化性心血管疾病。它是一种高度复杂的大环肽，具有大量的非肽结构元素，对合成化学提出了艰巨的挑战。我们描述了一种聚合、高效和稳健的制造工艺的发展，这种工艺能够大规模生产烯丙酸。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the American Chemical Society 化学-化学综合

CiteScore

24.40

自引率

6.00%

发文量

2398

审稿时长

1.6 months

期刊介绍： The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.