An improved stereoselective synthesis of (1R,2S,3S,4R,5R)-4-amino-5-(hydroxymethyl)- cyclopentane-1,2,3-triol

Iminosugars are sugar mimetics present in plants and microorganisms that were first reported in the1960s.[1] They can formally resulted from the replacement of the endocyclic oxygen atoms monosaccharides by a basic nitrogen and the lack of the anomeric hydroxy group (Figure 1). Taking into account their ability to inhibit carbohydrate-processing enzymes such as glucosidases, they have been proposed as a source for therapeutic agents.[2] Thus, two derivatives of the natural iminosugar deoxynojirimycin (DNJ) are now marketed drugs: miglitol for the treatment of type 2 diabetes and miglustat for the treatment of the lysosomal storage disorders Gaucher’s and Nieman–Pick type 2 diseases.

Aminocyclopentitols are also inhibitors of glucosidases that can be considered as carbohydrate mimics resulting from the lack of the endocyclic oxygen atom of furanoses and that carry an exocyclic amino group[3] Similarly to the deoxynojirimycins, they are mimicking either the protonated glycoside[4] or the intermediate glycosyl (oxycarbenium) cation.[5]

As part of our continued interest on glycosidase inhibitors, we will report an improved stereoselective synthesis of aminocyclopentitol V.

The oxidation of this compound V to the corresponding 2,3,4-trihydroxy-5-aminocyclopentanecarboxylic acid will also be discussed.