Lauryl and stearyl thioglycosides were prepared by the Lewis acid catalyzed reaction of 1-O-acetylated sugars with non-volatile and almost odorless 1-dodecanethiol and 1-octade- canethiol, respectively. These thioglycosides were activated by N-iodosuccinimide-TfOH to glycosyl donors producing disac- charides in good yields. Thioglycosides are quite versatile intermediates in oligosaccharide synthesis due to their ease of preparation and activation by a potent thiophilic reagent that affords highly reactive glycosylating reagents. 1 Furthermore, a distinct advan- tage of the thioglycosides is that the hemithioacetal function can serve as a temporary protecting group stable under various conditions for chemical transformations of their hydroxyl groups. 2 Although the phenyl and ethyl thioglycosides are the most commonly used glycosyl donors, it is not easy to perform comfortably the preparation of these compounds using standard procedures even in a closed system or a well-organized draft chamber because of the pervasive stench of the volatile thiols. In this communication, we describe the preparation of the thio- glycosides of almost non-volatile mercaptans and applicability to the glycoside synthesis. In a similar way as described for the preparation of ethyl and phenyl thioglycosides, 3 pentaacetyl-β-D-glucopyranose 1 and its 3-O-benzyl derivative 4 2 were treated with 2 molar equivalents of 1-dodecanethiol (bp = 266 °C) and 1-octade- canethiol (mp = 18-20 °C) in the presence of BF 3 ⋅ OEt 2 (1 equiv) in 1,2-dichloroethane. The reactions completed at room temperature for 30 min to give the corresponding thioglyco- sides 5 (3a, 3b, 4a) in almost quantitative yields. This reaction was applicable to such disaccharides as fully acylated lactose and laminaribiose without cleavage of their glycosidic bonds. After Zemplèn deacetylation of 3a and 3b, the resulting tetraols were treated with benzoyl chloride or pivaloyl chloride in pyri- dine, thus giving the fully acylated thioglycosides 5 (5a, 5b, 6b) in more than 90% overall yields. However, conventional ben- zylation of the thioglycosides in DMF was unsuccessful, since aggregation of the starting material occurred during the reac- tion. This problem was overcome by carrying out the reaction under less polar conditions. Thus, benzylation of the lauryl thioglucoside with benzyl bromide-NaH in DMF-THF (2:1) and phase-transfer benzylation 6 of the stearyl thioglucoside in CH 2 Cl 2 -aq NaOH afforded the corresponding perbenzylated derivatives 5 (7a, 7b) in 64% and 77% yield, respectively. Next, applicability to various chemical modifications was examined, employing the lauryl thioglucoside 4a as the model compound. Saponification of 4a in aq KOH gave a lipophilic triol, which was isolated by usual extractive work-up in chloro- form. The resulting triol was treated with α,α-dimethoxy- toluene (DMT) in DMF in the presence of camphorsulfonic acid (CSA) to give the 4,6-O-benzylidene derivative 8, of which the 2-hydroxyl group was benzoylated in a one-pot man- ner to give the fully protected derivative 5 9 in 74% overall yield from 4a. By reductive ring opening of the benzylidene group with BH 3 ⋅NHMe 2 -BF 3 ⋅OEt 2 7 in CH 2 Cl 2 , 9 was converted into the 3,4-di-O-benzyl derivative 5 10. These results suggested that most of the conventional methods for the protection of the hydroxyl groups of the monosaccharides were applicable to these amphiphilic thioglycosides. Next, our interest focused on the behavior of these lauryl and stearyl thioglycosides during the glycosylation reaction. Upon activation with N-iodosuccinimide (NIS)-TfOH 8 in CH 2 Cl 2 in the presence of molecular sieves 4A (MS 4A) at –20 °C for 20 min, the thioglycosides (3ab, 5ab, 6b, 7ab) were reacted with methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside 11 to give the disaccharides 5 12. These results are summarized in Table 1. As expected, the acyl protecting donors predominant- ly afforded the β-linked disaccharides, i.e., cellobiose deriva- tives. Among several thioglycosides, the best results were obtained when we used the fully benzoylated lauryl thiogluco- side 5a. It produced the disaccharide 12 (R 2 = Bz) in greater 326 Chemistry Letters 2000 Copyright © 2000 The Chemical Society of Japan Lauryl and Stearyl Thioglycosides: Preparation and Reactivity of the Glycosyl Donor Hideaki Matsui, Jun-ichi Furukawa, Takuro Awano, Norio Nishi, and Nobuo Sakairi* Division of Bioscience, Graduate School of Environmental Earth Science, Hokkaido University, Kita-ku, Sapporo 060-0810 (Received December 9, 1999; CL-991041)