Synthesis of Trisaccharides by Hetero‐Diels–Alder Welding of Two Monosaccharide Units

Abstract

AbstractA new strategy for the synthesis of di‐ and trisaccharides based on the de novo synthesis of the linking saccharide unit is presented. In this strategy, functionalized monosaccharide building blocks already incorporating the glycosidic linkages are welded together using a metal‐catalyzed hetero‐Diels–Alder (HDA) reaction to generate a new monosaccharide unit between them. The highest yields and selectivities in the HDA reaction were obtained by using chiral Schiff base chromium complexes. Disaccharide products were accessible by reaction of Danishefsky's diene with acetyl‐ and benzyl‐protected galactoside aldehydes. For the synthesis of trisaccharide products, acetyl‐protected glucose or galactose‐derived dienes were fused with monosaccharide‐derived aldehydes using chromium catalysts for the HDA reaction. The desired trisaccharide products were obtained in moderate to good yields with excellent stereoselectivity. The central pyranulose‐ring generated in the process possessed an L‐cis‐enulose configuration according to NMR spectroscopy and modeling studies.