title: One-pot SSA-catalyzed β-elimination: an efficient and inexpensive protocol for easy access to the glycal of sialic acid.
abstract: Neu5Ac2en1Me per-OAc, the fully protected glycal of sialic acid, is a key intermediate in the discovery of therapeutics and diagnostics, including anti-influenza drugs and proteolysis resistant peptidomimetic foldamers. The synthesis of this sialic acid derivative, however, still relies on standard sugar chemistry that utilizes multi-step methodologies. Herein we report a facile and highly efficient microwave-assisted preparation of Neu5Ac1Me using silica sulfuric acid (SSA) as solid-supported acid catalyst that is one- to two-orders of magnitude faster than standard procedures. We also describe the microwave-assisted and SSA-catalyzed one-pot, rapid, solvent free reaction that combines both peracetylation and β-elimination reactions in one step to generate the glycal from Neu5Ac1Me. We coined the term One-pot SSA-catalyzed Technology for β-Elimination Protocol (OneSTEP) to describe this least laborious, most efficient, and practical preparation to date of Neu5Ac2en1Me per-OAc in terms of yield, time, reagent cost, and waste generation.
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: Erickson M
authors.initials: EM
authors.lastname: Paragas
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: I Abrrey
authors.initials: IA
authors.lastname: Monreal
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Vasil
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164, USA. Electronic address: jonel.saludes@wsu.edu.
authors.forename: Jonel P
authors.initials: JP
authors.lastname: Saludes
mesh_terms: D002384:Catalysis; D004987:Ethers / Q000737:chemistry*; D008872:Microwaves; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D013464:Sulfuric Acids / Q000737:chemistry*
chemical_list: D004987:Ethers; D013464:Sulfuric Acids; D012822:Silicon Dioxide; D019158:N-Acetylneuraminic Acid; C033158:sulfuric acid
keywords: 4-epi-Neu5Ac2en; Acetic anhydride; Microwave synthesis; Neu5Ac2en; Sialic acid; Silica sulfuric acid