Synthesis of a Comprehensive Polyprenol Library for Evaluation of Bacterial Enzyme Lipid Substrate Specificity.

Polyprenols, a universal class of glycan-carrier lipids, play important roles in glycan biosynthesis in wide variety of living organisms. The chemical synthesis of natural polyisoprenols such as undecaprenol and dolichols, and even more so the synthesis of their homologs, could serve as a powerful way to investigate and define the functions of enzymes involved in glycan biosynthesis. In this paper, we report an efficient and reliable method to construct this type of hydrophoic molecule using a base-mediated iterative coupling approach based on a key bifunctional (Z,Z)-diisoprenyl building block. The ligation of N-acetyl-D-glactosamine (GalNAc) with a set of the synthesized lipid analogs to form polyprenol-pyrophosphate-linked GalNAc (GalNAc-PP-lipid) conjugates is also demonstrated.