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

Org Biomol Chem. 2020 Nov 12;18(43):8899-8907. doi: 10.1039/d0ob01722a.

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.

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucagon-Like Peptide 1* / chemistry
  • Glucagon-Like Peptide 1* / metabolism
  • Humans
  • Molecular Structure
  • Signal Transduction* / drug effects
  • Trigonella / chemistry

Substances

  • Glucagon-Like Peptide 1