One-Pot Synthesis of Pyrrolidine-2-ones from Erythruronolactone and Amine

Concise and accessible approaches to pyrrolidine-2-ones were studied. The synthesis involves the conversion of erythruronolactone to pyrrolidine-2-ones in good yields. 1. Introduction Many pyranoses and furanoses with the ring oxygen replaced by an amino group, known as imino sugars or azasugars, have been found to inhibit specific enzymes such us glycosidases [1]. Inhibition of these enzymes which catalyze the hydrolysis of the glycosidic bond to residues of oligosaccharides or saccharides is a potentially useful target of a wide range of important biological processes, such as intestinal digestion and posttranslational processing of glycoproteins [2], cancer [3], and diabetes [4] and other metabolic disorders [5]. Most inhibitors of glycosidases described to date are mimics of the supposed transition state oxocarbenium [6]. The azasugars or iminosugars [7–9] are structures that are the most widely used. Members of this class include 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) (1) that was first isolated from leaves of derris elliptica (Fabaceae) [10] and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) (2) that was first found in the fruits of angylocalyx boutiqueanus (Fabaceae) [11]. They are selective inhibitors of glycosidase [12] (Figure 1). Figure 1: Inhibitors of glycosidase. The 1,4-dideoxy-1,4-imino-L-arabinitol (LAB, 3) (Figure 2) was first found in the fruits of angylocalyx boutiqueanus (Fabaceae) [11], which is a powerful inhibitor of sucrase and α-glucosidases [13]. Figure 2: LAB 3 and streptopyrrolidine 4. Recently, cis-5-benzyl-4-hydroxy-2-pyrrolidinone 4, named as streptopyrrolidine, was isolated from the fermentation of the broth of marine Streptomyces [14] (Figure 2). This compound exhibited significant antiangiogenesis activity and is expected to be a unique small-molecule bioprobe for studying angiogenesis. To combine the importance of the compounds 2, 3, and 4 we have decided to conduct a modification of compound 3 at the hydroxyl groups and alkylation of the nitrogen atom. Our aim is to study the influence of the N-alkyl chain on the inhibition of glycosidases for treating antiviral infection such as hepatitis C. Their synthesis is of great importance. Many methodologies for the synthesis of pyrrolidine iminosugars were developed. The nitrogen introduction often involves azide substitution [15] or oximation [16]. Heavy-metal catalysis was also widely used to install ring systems or hydroxyl groups [17]. Most of these methods are restricted requiring harsh reaction conditions, with low moderate yields and relatively long time, and