The synthesis of mycobacterial dimycoloyl diarabinoglycerol based on defined synthetic mycolic acids

Abstract

 Complex mixtures of natural dimycoloyl diarabinoglycerols isolated from mycobacteria have been shown to be potent immune signalling agents and potentially valuable antigens in the serodiagnosis of mycobacterial infections.  We now report the highly stereocontrolled synthesis of diacyl L-glycerol-(1'→1)-β-D-arabinofuranosyl-α-D-arabinofuranosides based on simple fatty acids and single defined synthetic mycolic acids.  NMR analysis confirmed that the synthetic core was identical to that in natural mixtures.

Lipids of Clinically Significant Mycobacteria

“…were initially characterized from the MAIS complex (Watanabe et al 1992(Watanabe et al , 1999, but they are more widespread including M. tuberculosis (Rombouts et al 2012) and M. marinum (Elass-Rochard et al 2012). Synthetic studies indicated that these lipids are based on substituted glycerols with L-configuration (Ali et al 2019).…”

Synthesis of a Di-Mycoloyl Tri-Arabinofuranosyl Glycerol Fragment of the Mycobacterial Cell Wall, Based on Synthetic Mycolic Acids

“…We have already reported the synthesis of triarabinose dimycolates [25], of arabinoglycerol mycolates [19], and of DMAGs containing unique synthetic mycolic acids [26]. Although, so far, it has no reported bioactivity, we now report the extension of the methods used in those synthetic approaches to the synthesis of a single stereoisomer of tri-arabinofuranosyl glycerol (TAG) and of a series of stereo-defined DMTAG glycolipids (Figure 1), through esterification of the glycan with structurally defined synthetic MAs of α- and keto-classes [1,2].…”