Synthesis of 1-Deoxynojirimycin: Exploration of Optimised Conditions for Reductive Amidation and Separation of Epimers

Abstract

1-Deoxynojirimycin (DNJ), which has importance with respect to sugar processing enzymes, is a synthetic target for chemists. A key step in the synthesis of DNJ is the preparation of 2,3,4,6-tetra- O-benzyl-D-glucono-δ-lactam. By varying reaction parameters such as temperature, solvent and reducing reagent, improvements on previous methods are described. A novel approach for the synthesis of 2,3,4,6-tetra- O-benzyl-5-dehydro-5-deoxo-D-gluconamide has been developed by using PCC as an oxidising agent. Separation of epimers permitted DNJ to be obtained in 85% yield after reduction and hydrogenolysis steps.

Developments in Carbohydrate-Based Metzincin Inhibitors

“…Azasugars or iminosugars, whether of natural or synthetic origin, are hydroxylated carbohydrate mimics, where a basic nitrogen substitutes the classic endocyclic oxygen [ 85 ]. This modification appears simple and not significant but provides important biological properties and also gives rise to many synthetic challenges [ 86 , 87 , 88 , 89 , 90 , 91 , 92 ]. Historically, iminosugars are known as inhibitors of glycosidases, enzymes involved in the glycosidic bond hydrolysis in different biological processes, such as intestinal digestion, post-translational processing of the sugar chain of glycoproteins, and lysosomal catabolism of glycoconjugates [ 93 ].…”

Amino Acid-Based Synthesis and Glycosidase Inhibition of Cyclopropane-Containing Iminosugars

“…The development of efficient routes for the preparation of iminosugars has received much attention from the synthetic community . Most of the methods use carbohydrates as the chiral pool, which are transformed using reductive aminations or other transformation strategies . Alternatively, some asymmetric or biocatalysed approaches have been used .…”