Efficient Routes to Ethyl‐2‐Deoxy‐2‐phthalimido‐1‐β‐D‐thio‐galactosamine Derivatives via Epimerization of the Corresponding Glucosamine Compounds

Abstract

Short synthetic routes to protected ethyl 2‐deoxy‐2‐phthalimido‐1‐β‐D‐thio‐galactosamine derivatives via epimerization of the corresponding glucosamine compounds are described. Starting from D‐glucosamine hydrochloride, the epimerizations were performed by displacement of presynthesized triflates with nitrite anions and by an oxidation/reduction route. The latter method involved Moffatt oxidation to the corresponding 4‐ketohexoses and subsequent reduction using sodium borohydride/tetrabutylammonium borohydride, zinc borohydride, or lithium tri‐sec‐butyl borohydride in THF. The displacement route was found to be the preferred method for epimerization of 3‐O‐acyl (benzoyl) derivatives. For glucosamine compounds with 3‐O‐etheral‐ (allyl or benzyl) and 6‐O‐benzyl protecting groups, the oxidation/reduction route was the most convenient procedure to achieve corresponding galactosamine compounds. The produced galactosamine derivatives will be useful building blocks in the synthesis of antifreeze glycoproteins substances and analogues thereof.

Keywords:

• Galactosamine
• Epimerization
• Oligosaccharides
• Glycosyl donors
• Antifreeze glycoproteins

Acknowledgments

We would like to thank the Swedish Research Council and the Swedish Foundation for Strategical Research through the Biomimetic Materials Science program for financial support.