Synthesis of Lipid-Linked Arabinofuranose Donors for Glycosyltransferases

• Published in: Journal of organic chemistry Vol. 78; no. 5; pp. 2128 - 2133
• Main Authors: Kraft, Matthew B, Martinez Farias, Mario A, Kiessling, Laura L
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-03-2013
• Subjects: Arabinose - analogs & derivatives; Arabinose - chemical synthesis; Arabinose - chemistry; Cell Wall - chemistry; Cell Wall - metabolism; Glycolipids - chemistry; Glycosyltransferases - chemistry; Glycosyltransferases - metabolism; Lipids - chemistry; Molecular Structure; Mycobacterium - chemistry; Polyisoprenyl Phosphates - chemistry; Stereoisomerism; Substrate Specificity
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo302507p

Mycobacteria and corynebacteria use decaprenylphosphoryl-β-d-arabinofuranose (DPA) as a critical cell wall building block. Arabinofuranosyltransferases that process this substrate to mediate cell wall assembly have served as drug targets, but little is known about the substrate specificity of any of these enzymes. To probe substrate recognition of DPA, we developed a general and efficient synthetic route to β-d-arabinofuranosyl phosphodiesters. In this approach, the key glycosyl phosphodiester bond-forming reaction proceeds with high β-selectivity. In addition to its stereoselectivity, our route provides the means to readily access a variety of different lipid analogues, including aliphatic and polyprenyl substrates.