ArticlePrecision chemistry2026
Efficient Synthesis of Enlicitide Chloride through Convergent Solution-Phase and Hybrid Solution-Solid-Phase Strategies.
Article in Precision chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Elevated low-density lipoprotein cholesterol (LDL-C) is a prominent risk factor for developing atherosclerotic cardiovascular disease (ASCVD), which is presumably triggered by abnormal binding between the proprotein convertase subtilisin/kexin-type 9 (PCSK9) and low-density lipoprotein receptors (LDLR). Enlicitide is a PCSK9 inhibitor with an unusual structure and tremendous potential for the treatment of ASCVD. This bioactive tricyclic peptide provides an interesting structural motif for exploring medicinal chemistry studies and developing more orally administered peptide therapeutics with potent hypolipidemic abilities. Herein, we report two efficient and robust preparation processes that enable the total synthesis of enlicitide, including a fully solution-phase synthetic strategy and a hybrid solution-solid-phase strategy. Critically, the combination of Fmoc-based solid-phase peptide synthesis (SPPS) and solution-phase ring-closing reactions enables the time-effective preparation of enlicitide, paving the way for its structural diversification and the further development of enlicitide-based medications.
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