TETRAHEDRON LETTERS Tetrahedron Letters 44 (2003) 7961–7964 Pergamon Reaction of 1,2-trans -glycosyl acetates with thiourea: a new entry to 1-thiosugars Farid M. Ibatullin, a, * Konstantin A. Shabalin, a Janne V. Ja ¨nis b and Alexander G. Shavva c a Molecular and Radiation Biophysics Division, Petersburg Nuclear Physics Institute, Gatchina 188300, Russia b Department of Chemistry, University of Joensuu, Joensuu, Finland c Chemical Department of Petersburg State University, St.-Petersburg, Russia Received 14 July 2003; revised 20 August 2003; accepted 29 August 2003 Abstract—The reaction of 1,2-trans -glycosyl acetates with thiourea under boron trifluoride etherate catalysis affording acetylated S -glycosyl isothiourea derivatives is described. The isothiourea derivatives obtained can be readily transformed into the desired 1-thiosugar derivative by reaction with triethylamine and subsequent alkylation or acylation of the in situ formed 1-thioaldose. © 2003 Elsevier Ltd. All rights reserved. 1-Thiosugars have attracted considerable attention over the last decades. Due to their close structural similarity to the natural O -glycosides they have been widely used in biochemical 1 and structural 2 investigations of gly- cosidases. Owing to the stability of a thioglycosidic bond to enzymatic cleavage, thioglycosides have been considered as very promising candidates for the prepa- ration of carbohydrate-based therapeutics. 3 Thiogly- cosides have found wide applications in carbohydrate chemistry as very convenient glycosyl donors. The cur- rent progress in the synthesis of complex oligosaccha- rides has been greatly related to the development of new versatile glycosylation methods utilizing thiogly- cosides as glycosyl donors. 4 The Lewis acid catalyzed reaction of per-O -acetylated sugars with alkyl or aryl thiols 5 is one of the most often employed approaches for the synthesis of 1-thiogly- cosides. The method allows synthesizing target com- pounds in one step directly from readily available peracetylated sugars, although it often suffers from a number of drawbacks, including the necessity of work- ing with malodorous and toxic mercaptans. This method often leads to the formation of anomerized products. Alternatively, the conversion can be performed using alkyl- or arylthiotrimethylsilanes, 6 although they are less available than thiols and, therefore, require special preparation. One of the most convenient and simple approaches for the stereoselective synthesis of 1,2-trans -thioglycosides is based upon utilization of S -glycosyl isothiourea derivatives as starting compounds. 7 Recently, we have shown that isothiourea derivatives of sugars can also be successfully applied for the synthesis of thiodisaccharides 8 and thiooligosaccharides. 9 Up to now, the only method for the preparation of S -glycosyl isothiourea derivatives is the reaction of thiourea with glycosyl halides, 7 that are generally pre- pared from sugar peracetates. However, sugar peracetates can also be used as very convenient glycosyl-donors, that have been widely uti- lized for glycosylation of various compounds, 10 includ- ing thiols 5 and thioacetic acid. 11 Nevertheless, no attempt has been made to investigate such reactions with thiourea, which might be a convenient approach to S -glycosyl isothiourea derivatives, and consequently to thioglycosides, avoiding the use of mercaptans and the halogenose preparation step. Therefore, in the course of our current research 12 and interest in thioglycoside synthesis, we decided to investi- gate the reactivity of per-O -acetylated sugars with thiourea. Thiourea readily reacts with various electrophiles, including carbenium ions, affording S -alkyl isothiouro- nium salts. So, reactions of thiourea with alkyl alco- hols, 13 oxetanes, 14 or with benzoquinones 15 under strongly acidic conditions seem to proceed through a * Corresponding author. 0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2003.08.120