Rapid Preparation of Mycobacterium N-Glycolyl Lipid I and Lipid II Derivatives: A Biocatalytic Approach

Breaking down barriers: A rapid, inexpensive preparation of the structurally complex mycobacterial N‐glycolyl Lipid I, Lipid II, and their analogues from a range of different synthetic N‐glycolyl and N‐glycinyl Park's nucleotides is described (see scheme). The biotransformations were catalyzed by a readily available biocatalyst obtained from a bacterial cell‐free membrane fraction. The unnatural N‐glycinyl Lipid II was found to be a substrate of Mycobacterium tuberculosis (Mtb) transglycosylase, PonA, and N‐glycolyl Lipid I was a weak inhibitor against PonA.