Total synthesis and absolute structure of N55, a positive modulator of GLP-1 signaling

Abstract

Glucagon-like peptide-1 (GLP-1) signaling is an established therapeutic target for type 2 diabetes mellitus (T2DM). We developed a 7-step synthesis of N55, a positive modulator of GLP-1 signaling isolated from fenugreek (Trigonella foenum-graecum) seeds, with 29% overall yield, and we determined the absolute structure of N55 to be N-((3R,4R,5S)-4,5-dimethyl-2-oxotetrahydrofur-3-yl)linoleic amide.