The use of anhydroiminocyclitols as glycosyl donors in glycosidation reactions Jos  e Fuentes a, * , Nader R. Al Bujuq a , Manuel Angulo b , Consolaci  on Gasch a a Departamento de Qu  õmica Org anica, Universidad de Sevilla, Apartado 1203, E-41071 Sevilla, Spain b Servicio de RMN, Universidad de Sevilla, Apartado 1152, E-41071 Sevilla, Spain article info Article history: Received 12 May 2010 Received in revised form 7 September 2010 Accepted 17 September 2010 Available online 24 September 2010 Keywords: Iminosugar Iminocyclitol Azasugar Glycosyl donor Glycosidation reaction Thioglycoside Glycoside abstract High yielding synthesis of six- and five-membered N-substituted iminosugar glycosides and of five- membered iminosugar thioglycosides by nucleophilic opening of both new and previously described N- diethoxycarbonylvinyl anhydroiminosugar derivatives (glycosyl donors) with primary alcohols, primary thiols, and thiophenol (glycosyl acceptors) is reported. The reactions are highly stereoselective, with anomeric ratios better than 4:1. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction In the past decade the stereoselective syntheses of highly functionalized molecules, such as natural and pharmaceutically important compounds, have been a challenge in organic chemis- try. 1 Carbohydrate derivatives, due to their numerous stereogenic centers, anomeric reactivity, and conformational properties, play an important role in these syntheses, where can be considered as targets or as key chiral intermediates. 2 Particularly, iminocyclitols, also known as iminosugars, are glycosidase and glycosyltransferase inhibitors and consequently they can be useful in the treatment of metabolic disorders and inflammatory processes. 3,4 It is not sur- prising that this therapeutical potential has generated a huge in- terest in the syntheses and structural modifications of iminosugars, and many short and stereoselective routes have been reported. 5 We have described a versatile procedure to prepare five 6 -, six 7 -, and seven 8 -membered iminosugars, starting from glycosylenamines and being the key chiral intermediate an anhydroiminosugar. The data on the preparation of iminosugar glycosides (1) and iminosugar thioglycosides (2) are limited. Multistep, low-yielding syntheses of 2-alkoxy polyhydroxypiperidines have been repor- ted. 9,10 Six-membered iminosugar glycosides have been used as intermediates to prepare monocyclic 11e13 and bicyclic azasugars. 14 A method for the synthesis of six-membered azasugar glycosides and thioglycosides starting from 1,2-O-isopropylidene furanosyl derivatives has been reported by Schmidt. 15 The author has used the glycosidation reaction, with trichloroacetimidates as glycosyl donors, to prepare nojirimycin thioglycosides. 16 Hashimoto 17 has reported the first synthesis of an ethyl thioglycoside of a thio- disaccharide having one iminosugar moiety. Later, we have de- scribed 18 the synthesis of six-membered iminosugar thioglycosides starting from an anhydroiminosugar with D-ribo configuration. Regarding the preparation of five-membered iminosugar gly- cosides, Schmidt 19 has described a multistep synthesis of a methyl iminoriboside, and we have reported 20 the preliminary data on the use of an anhydroiminocyclitol, particularly with D-galacto config- uration, as glycosyl donor in glycosidation reactions, but only methanol was used as glycosyl acceptor. The bibliographic data on five-membered iminocyclitol derivatives having a thioalkoxy group on the pseudoanomeric carbon atom are very scarce, and limited to thioanalogues of the indolizidine alkaloid castanospermine having the sulfur atom taking part in the five-membered ring. 21 * Corresponding author. Tel.: þ34 954551518; fax: þ34 954624960; e-mail address: jfuentes@us.es (J. Fuentes). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2010.09.065 Tetrahedron 66 (2010) 9214e9222