Facile and Sustainable Synthesis of Commendamide and its Analogues

Rosaria Villano; Francesco Tinto; Vincenzo Di Marzo

doi:10.3389/fchem.2022.858854

Facile and Sustainable Synthesis of Commendamide and its Analogues

Front Chem. 2022 Mar 1:10:858854. doi: 10.3389/fchem.2022.858854. eCollection 2022.

Authors

Rosaria Villano¹, Francesco Tinto², Vincenzo Di Marzo^{1

3}

Affiliations

¹ Istituto di Chimica Biomolecolare, Pozzuoli, Italy.
² Département de Médecine, Faculté de Médecine, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada.
³ Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Faculty of Medicine and Faculty of Agricultural and Food Sciences, Centre NUTRISS, Centre de Recherche de l'Institut de Cardiologie et Pneumologie de l'Université et Institut sur la Nutrition et les Aliments Fonctionnels, Université Laval, Quebec City, QC, Canada.

Abstract

Commendamide, or N-(3-hydroxypalmitoyl)-glycine 1a, is a gut microbiota-derived bioactive metabolite, structurally similar to long-chain N-acyl-amino acids which belong to the complex lipid signaling system known as endocannabinoidome and play important roles in mammals through activation of, inter alia, G-protein-coupled receptors (GPCRs). In this work, we describe a simple, green and economic method for the preparation of commendamide 1a, a GPCR G2A/132 agonist. The developed protocol is general and could also be applied to the synthesis of deuterated commendamide 1b, as well as to other minor microbiota-derived metabolites, such as the analog 2.

Keywords: commendamide; drug discovery; endocannabinoidome; green chemistry; microbiota; organic synthesis.