Synthesis of <i>N</i>-(3-Acyloxyacyl)glycines, Small Molecules with Potential Role in Gut Microbiome-Endocannabinoidome Communication

Abstract

The synthesis of some N-(3-acyloxyacyl)glycines, an interesting class of bioactive gut microbiota metabolites, is described. This procedure involves seven reaction steps using the commercially available Meldrum’s acid to obtain highly pure products, in normal or deuterated form. The key point of the synthetic strategy was the use of commendamide t-butyl ester as a synthetic intermediate, a choice that allowed the removal of the protecting group at the end of the synthetic procedure without degrading of the other ester bond present in the molecule. The developed synthetic sequence is particularly simple, uses readily available reagents and involves a limited number of purifications by chromatographic column, with a reduction in the volume of solvent and energy used.

Keywords

• organic synthesis
• <i>N</i>-(3-acyloxyacyl)glycines
• <i>N</i>-acyl amino acids
• gut microbiota metabolites
• endocannabinoidome