New 1,2,3-Triazole Iminosugars Derivatives Using Click Chemistry

The click concept refers ease, efficient, and the selective chemicals transformations. In this study, a novel regiospecific copper (I)-catalyzed 1, 3-dipolar of terminal alkynes to azide provided a practicable synthetic pathway of triazole iminosugars derivatives. A series of new triazole-pyrrolidinols are reported in good yield. 1. Introduction There are considerable interests in the design of molecules that are able to mimic carbohydrates which play critical roles in various biological events. This is shown by the following example, the 1-deoxynojirimycin (DNJ) family, for which DNJ itself is a competitive inhibitor of α-D-glucosidase ( 25？μM) [1], while its derivatives Miglustat (N-nBu DNJ, Zavesa) and Miglitol (N-hydroxyethyl DNJ, Glyset, or Diastabol) have already found therapeutic applications in Gaucher’s disease [2] and type 2 (noninsulin-dependant mellitus) diabetes, respectively [3, 4] (Figure 1). Recently, researches have increasingly accorded to new iminosugars from click chemistry [5]. Figure 1: Structure of inhibitors of glycosidases. The term click chemistry was introduced by Sharpless and coworkers and promotes the use of efficient, selective, and versatile chemical reactions in synthetic chemistry [6]. The basic reaction, which is nowadays summed up under the name “Sharpless-type click reaction,” is a variant of the Huisgen 1,3-dipolar cycloaddition reaction between C–C triple bonds and alkyl azides [7, 8] (Scheme 1). Scheme 1: 1,3-dipolar cycloaddition reaction. Meldal and coworkers published a paper in 2002 that describes the acceleration of this process by CuI salts that leads to a reaction at 25°C in quantitative yields. It was mentioned that the organic azides and the terminal alkynes are united to afford 1,4-regioisomers of 1,2,3-trialoes as sole products [9]. The source of Cu(I) salts commonly used involves the reduction of copper(II) sulfate by sodium ascorbate [9], although other conditions have been described, such as Cu(I) [10] salts, Cu(I) complexes [11] and stabilized derivatives of Cu(I) [9]. The bases used are mostly triethylamine, 2,6-lutidine and N,N-diisopropylethylamine (DIPEA). 1.1. Click Chemistry and Synthesis of Iminosugars Derivatives The application of CuAAC-catalysed reactions for the synthesis of new α-glucosidase inhibitors containing a 1-deoxynojirimycin (DNJ) was described by Murphy and coworkers. These compounds indicate that it is possible to modulate the potency and the selectivity towards different glycosidases [5] (Figure 2). Figure 2: Structures of triazole iminosugars as potential glycosidase