A survey of chemical methods for sugar-nucleotide synthesis

Abstract

Covering: up to 2009

Sugar-nucleotides are essential intermediates in carbohydrate metabolism and glycoconjugate biosynthesis. Structurally, sugar-nucleotides are composed of a sugar or sugar derivative and a nucleoside mono- or diphosphate. Numerous combinations of sugars and nucleotides are found in nature, and although only nine different sugar-nucleotides have so far been identified in mammalian cells, this number is much greater in other organisms. Naturally occurring sugar-nucleotides, as well as structural analogues, are of great interest as substrates for enzymatic reactions in carbohydrate synthesis, as enzyme inhibitors, as tools for assay development and for the study of glycoconjugate biosynthesis. Therefore, methods for the efficient preparation of natural and non-natural sugar-nucleotides are of considerable importance for synthetic, biological and medicinal chemistry. The synthesis of sugar-nucleotides is non-trivial and complicated by a number of factors: the low solubility of sugar-nucleotides in organic solvents, the presence of several polar or charged functional groups, and the susceptibility of the glycosidic and pyrophosphate bonds to hydrolytic cleavage. To address these issues, both chemical and enzymatic strategies have been pursued. Here we present an overview of current methods for the chemical synthesis of NDP- and NMP-sugars, including recently developed protocols for the direct chemical manipulation of unprotected sugar-nucleotides.