Synthesis of Positional Thiol Analogs of β‐D‐Galactopyranose

Abstract

AbstractApproaches toward the synthesis of thio‐β‐D‐galactose derivatives are described. These compounds were prepared from the parent carbohydrates: D‐galactose, methyl β‐D‐galactoside and methyl β‐D‐glucoside, respectively. It was found that not only the strategies of protecting group introduction and selective deprotection, but also the choices of solvent and nucleophilic reagent concentration were crucial to allow the efficient introduction of sulfur at different positions of the galactose ring. The effects from the solvent, the nucleophilic reagent concentration, and the protecting group patterns have been investigated. The results clearly show that ester protecting groups play highly important roles for the synthesis of thio‐containing carbohydrates, requiring nonpolar solvents to suppress the neighboring group participation. For the Lattrell–Dax (nitrite‐mediated) inversion reaction, employed in the synthetic route to the 2‐thio‐β‐D‐galactoside, intramolecular nucleophilic attack, as well as strongerstereospecific ester activation, are necessary to overcome hindrance from 4,6‐O‐benzylidene protection.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)