This journal is © The Royal Society of Chemistry 2014 Chem. Commun., 2014, 50, 1549--1551 | 1549 Cite this: Chem. Commun., 2014, 50, 1549 A diversity oriented one-pot synthesis of novel iminosugar C-glycosides† Soundararasu Senthilkumar, Sure Siva Prasad, Ponminor Senthil Kumar and Sundarababu Baskaran* A mild and highly efficient one-pot method has been developed for the stereoselective synthesis of structurally diverse novel iminosugar C-aryl glycosides. The generality of this methodology is demonstrated with a wide variety of aryl nucleophiles and amines. The synthetic potential of this methodology is further shown in the domino synthesis of iminosugar based hybrid molecules. Ever since the discovery of iminosugars as potent glycosidase inhibitors, they have evoked considerable interest at the interface between medicinal chemistry, glycobiology and organic synthesis. 1 The broad spectrum of biological activities displayed by iminosugars has widened their scope towards the inhibition of various enzymes of medicinal interest such as glycosyltransferases, glycogen phosphorylases, nucleoside-processing enzymes and metalloproteinases. 1,2 Moreover, iminosugars serve as potential molecules in probing active sites as well as the allosteric interactions with carbohydrate-processing enzymes (CPEs). 1 Thus, because of their biomimetic properties, iminosugars are becoming important lead molecules for drug development in a variety of therapeutic areas including diabetes, viral infections and tumor metastases. Recent biological studies have suggested that the presence of alkyl/aryl substituents on iminosugars often leads to an increase in potency and specificity. 3 This is further supported by the enhanced anticancer as well as the ceramide glucosyltransferase inhibitory activities displayed by N-alkylated iminosugars. 4 As a consequence, there has been ever-growing interest towards achieving a simple, general and reliable synthesis of various N-/C1-alkyl/aryl substituted iminosugars for a wide spectrum of biological evaluations. 5 In this communication, we report a mild and highly efficient method for the diversity oriented one-pot synthesis of novel imino- sugar C-aryl glycosides via stereoselective arylation of in situ generated iminium ions with various aryl nucleophiles (Scheme 1). Thus, treatment of D-ribose tosylate 1 at room temperature with benzyl amine and subsequent stereoselective arylation of the in situ generated iminium ions with b-naphthol (2) resulted in the isolation of a functionalized iminosugar b-C-glycoside 3 as the only product in 88% yield (Scheme 2). 6 The structure and stereo- chemistry of the iminosugar b-C-glycoside 3 was unambiguously confirmed using single crystal X-ray analysis. 7a Encouraged by the efficacy of this transformation, the generality of this reaction was tested using a wide variety of amines and carbon nucleophiles and the results are summarized in Table 1. Stereoselective arylation of the in situ generated iminium ions, derived from tosylate 1 using various amines, with resorcinol (4) resulted in the isolation of the corresponding iminosugar b- C-glycosides 5, 6, 7 and 8 respectively in very good yields (Table 1, entry 1). Similarly iminium ions, derived from benzyl- amine and tosylate 1, on arylation with pyrogallol (9) and m-amino phenol (11) afforded the corresponding iminosugar b- C-glycosides 10 and 12, respectively, in 84% and 80% yield (Table 1, entries 2 and 3). Under similar reaction conditions, the heteroaromatics such as indole (13) and pyrrole (15) underwent a smooth reaction to Scheme 1 Synthesis of novel iminosugar b-C-aryl glycosides. Scheme 2 Synthesis of novel iminosugar b-C-aryl glycosides 3 from 1. Department of Chemistry, Indian Institute of Technology Madras, Chennai, 600036, India. E-mail: sbhaskar@iitm.ac.in; Fax: +91-44-22570545; Tel: +91-44-22574218 † Electronic supplementary information (ESI) available: Representative experi- mental procedure and characterization of reaction products. CCDC 931863– 931865. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3cc48370c Received 1st November 2013, Accepted 26th November 2013 DOI: 10.1039/c3cc48370c www.rsc.org/chemcomm ChemComm COMMUNICATION Published on 29 November 2013. Downloaded by Indian Institute of Technology Chennai on 09/12/2016 13:19:47. View Article Online View Journal | View Issue