Synthesis of N -Linked Amino-Hexyl Fluorotryptophan for Enlicitide, Part 2: Process Improvements toward Commercial Manufacture

Organic Process Research & Development 2026

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Authors: Kai‐Jiong Xiao, Yingju Xu, Alexandra C. Sun, E. B. Sirota, Byron K. Peters, Jeffrey T. Kuethe, Timothy J. Wright, Ralph Zhao, Gurpreet Longia, Erica L. Schwalm, Yongqian Zhang, Chengqian Xiao
+2 more 鲍永团, Sarah S. Co
DOI: 10.1021/acs.oprd.6c00256
Cited by: 1
References: 13

Abstract

Abstract Herein, we report the development of a robust manufacturing process for N-linked amino-hexyl fluorotryptophan 3, a key building block for enlicitide decanoate (MK-0616), which is an orally bioavailable inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). Targeted process development enabled safe operation of the Delépine reaction, increased yields for the hexamine hydrolysis and enzymatic tryptophan synthesis, and established a robust and selective N-alkylation of 5-fluorotryptophan. Collectively, these improvements afforded the target product with high yield, >98.5% purity, and favorable physical properties suitable for commercial manufacture.

Fields of Study & Subjects

Click Chemistry and Applications Monoclonal and Polyclonal Antibodies Research Biochemical and Structural Characterization

Publication details

Journal / source
Organic Process Research & Development
Publisher
American Chemical Society (ACS)
Volume
30
Issue
9
Pages
2540–2548
Publication date
31 August 2026
Language
EN