Synthesis of Glycosylated 1‐Deoxynojirimycins Starting from Natural and Synthetic Disaccharides

• Published in: European journal of organic chemistry Vol. 2019; no. 1; pp. 118 - 129
• Main Authors: Liu, Bing, van Mechelen, Jeanine, van den Berg, Richard J. B. H. N., van den Nieuwendijk, Adrianus M. C. H., Aerts, Johannes M. F. G., van der Marel, Gijsbert A., Codée, Jeroen D. C., Overkleeft, Herman S.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 10.01.2019; Wiley Subscription Services, Inc
• Subjects: Chemical synthesis; Chemistry; Chemistry, Organic; Deoxynojirimycin; Disaccharides; Glycosidase inhibitor; Glycosylation; Natural products; Oligosaccharides; Organic chemistry; Oxidation; Physical Sciences; Reductive amination; Science & Technology; Deoxynojirimycin; Reductive amination; Glycosidase inhibitor; POLYHYDROXYLATED ALKALOIDS; IMINOSUGARS; Glycosylation; ENZYMATIC-SYNTHESIS; Oligosaccharides; MORUS-ALBA; SUGARS; GALACTOSIDASE; INHIBITORS; MULBERRY LEAVES; CONCISE SYNTHESIS; DERIVATIVES
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201801461

Iminosugars are an important class of natural products and have been subject to extensive studies in organic synthesis, bioorganic chemistry and medicinal chemistry, yet only a limited number of these studies are on glycosylated iminosugars. Here, a general route of synthesis is presented towards glycosylated 1‐deoxynojirimycin derivatives based on the oxidation–reductive amination protocol that in the past has also been shown to be a versatile route towards 1‐deoxynojirimycin. The strategy can be applied on commercial disaccharides, as shown in four examples, as well as on disaccharides that are not commercially available and are synthesized for this purpose, as shown by a fifth example. The synthesis of five deoxynojirimycin‐configured aza‐disaccharides, starting from their corresponding disaccharides and featuring a double reductive amination on 5‐keto‐aldehydes, that returns the stereochemistry of the reducing end d‐glucopyranose is presented. As starting materials disaccharides, which are available in bulk, can be used, and alternatively be obtained by chemical synthesis.