Total Synthesis of Enlicitide Decanoate
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.
Authors
- Peter E. Maligres (ORCID: https://orcid.org/0000-0002-2237-9002)
- Baoqiang Wan
- Erik L. Regalado (ORCID: https://orcid.org/0000-0002-7352-6391)
- Nimisha Thakur (ORCID: https://orcid.org/0000-0002-6380-6613)
- Jing Xu (ORCID: https://orcid.org/0000-0002-5304-7350)
- Kerstin Zawatzky
- Jeffrey T. Kuethe (ORCID: https://orcid.org/0000-0001-8955-6010)
- Guiquan Liu (ORCID: https://orcid.org/0000-0003-0653-3935)
- M. Becker (ORCID: https://orcid.org/0000-0003-4259-6992)
- Louis‐Charles Campeau (ORCID: https://orcid.org/0000-0002-2373-802X)
- Paul G. Bulger (ORCID: https://orcid.org/0009-0008-0474-8485)
- Kai‐Jiong Xiao (ORCID: https://orcid.org/0000-0001-5613-2035)
- Gao Shang
- Kari Hullen
- Clara Hartmanshenn (ORCID: https://orcid.org/0000-0002-7779-7893)
- Artis Klapars (ORCID: https://orcid.org/0000-0002-6244-5502)
- Weijuan Tang (ORCID: https://orcid.org/0000-0002-8386-0764)
- Richard Desmond
- Justin A. Newman (ORCID: https://orcid.org/0000-0002-2498-1259)
- Marc Poirier
- Mirlinda Biba (ORCID: https://orcid.org/0000-0002-9888-0821)
- Qinghao Chen (ORCID: https://orcid.org/0000-0001-5735-4019)
- Jongrock Kong (ORCID: https://orcid.org/0000-0003-1509-687X)
- Narayan Variankaval
- Anagha Chandra (ORCID: https://orcid.org/0000-0001-7232-1880)
- Tiffany Piou (ORCID: https://orcid.org/0000-0003-4923-9138)
- Fuh-Rong Tsay
- Jimmy DaSilva (ORCID: https://orcid.org/0000-0001-7044-0640)
- Andrew Nolting (ORCID: https://orcid.org/0000-0002-2086-0476)
- Chengqian Xiao
- Xiaohui Cao (ORCID: https://orcid.org/0000-0003-2094-2444)
- Duan Jian-jun
- Smit Patel (ORCID: https://orcid.org/0000-0001-8414-6362)
- Lee Robison (ORCID: https://orcid.org/0000-0002-7419-4499)
- Carlos A. Pons Siepermann (ORCID: https://orcid.org/0000-0003-2839-776X)
- Jian‐Sheng Sun (ORCID: https://orcid.org/0000-0003-0614-1931)
- Ruxia Yi
- Christopher A. Strulson
- Reed T. Larson (ORCID: https://orcid.org/0000-0002-4462-2528)
- Meiqing Feng
- Nicholas R. Deprez (ORCID: https://orcid.org/0000-0003-3125-2959)
- David A. Thaisrivongs (ORCID: https://orcid.org/0000-0002-0387-8885)
- Kathleen P. Sokolowsky
- Biao Li (ORCID: https://orcid.org/0000-0002-3156-4381)
- Hongming Li (ORCID: https://orcid.org/0000-0001-6934-1928)
- Zhu Liu (ORCID: https://orcid.org/0000-0002-0074-1453)
- Yu He (ORCID: https://orcid.org/0009-0001-9069-9331)
- Joshua E.-Y. Lee (ORCID: https://orcid.org/0000-0002-1741-1485)
- Chen Lü (ORCID: https://orcid.org/0000-0003-1927-2391)
- Zhenhua Wu (ORCID: https://orcid.org/0000-0003-4552-883X)
- Lushi Tan
- Donghong Li (ORCID: https://orcid.org/0000-0002-5072-5988)
- Yawei Dong (ORCID: https://orcid.org/0000-0002-3126-3220)
- Anisha Patel (ORCID: https://orcid.org/0000-0002-3030-2961)
- Cody Welch
- Richard J. Varsolona
- Yongpeng Yuan
- Guangxin Shao
- Jingjun Yin
- Zhiyan Song
- Chris K. Prier
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Tianjin Economic-Technological Development Area (CN)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-03-24
- DOI
- https://doi.org/10.1021/jacs.4c15966
- Citations
- 30
- Primary Topic
- Biochemical and Molecular Research
- Type
- article
- Field-Weighted Citation Impact
- 24.18