Journal of Natural Sciences Research www.iiste.org ISSN 2224-3186 (Paper) ISSN 2225-0921 (Online) Vol.4, No.8, 2014 1 A New Approach for Preparing Methyl 6-azido-2,3,4-tri-O- benzyl-6-deoxy-alpha-D-glucopyranoside Ghassab M. Al-Mazaideh * and Rasheed M.A.Q. Jamhour Department of Chemistry and Chemical Technology, Faculty of Science, Tafila Technical University, P.O. Box 179, Tafila 66110, Jordan. * E-mail of the corresponding author: gmazideh@ttu.edu.jo Abstract: Azide sugars are key intermediates in the synthesis of aminglycosides, which themselves are useful for the synthesis of glycopeptides. A new method has been achieved by using DPPA and DBU in dry DMF with high temperature for replacement of the azide group from alcohol (glucoside) on the position 6. The results of this method are very important for preparing 6-azido sugar without needing to prepare and separate glucosyl halide completely. The proposed method was successfully applied with direct, simple, and time saving. In addition, excellent yield of 95% was obtained from azide, which could be used to obtain pharmaceutical active compounds. Keywords: Methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-glucopyranoside, DPPA, DBU, azides. 1. Introduction Recently, the synthesis of glycosyl azides and their applications has been one of the most important areas of research in chemistry and biochemistry. Moreover, azides are known as starting materials or a key intermediate in preparation of a number of biologically active compounds and aminglycosides, which can be used as glycosyl donors for the synthesis of glycopeptides and construction of heterocycles (Biswajit et al., 2008; de Oliveira et al., 2006; Wilkinson et al., 2006 & Rokhum and Bez, 2012). Due to their easily performed reduction to amines and their stability with reaction conditions, they can maintain amines against variety of carbohydrate synthesis such as ‘click chemistry’ (Lutz, 2007). Moreover, glycoproteins have many important functions like carriers, hormones, enzymes, lectins, antibodies, and receptors (Karlsson et al., 1993). A common way for the preparation of azido sugar is by nucleophilic substitution of the corresponding halides or sulfonates under classical homogeneous conditions by azide ion at the anomeric center (Alvarez and Alvarez, 1997). While elevated temperatures are often required in case of homogeneous one-phase reactions in DMF. The phase-transfer catalysis at milder conditions may cause instability of acetylated halides, which is considered as a major limitation of this method. These methodologies have been developed to avoid the preparation of glycosyl halides completely (Beckmann and Wittmann, 2010). Consequently, the direct method is used to convert acetylated sugars into acetylated 1-azide using trimethylsilyl azide in the presence of lewis acid catalysis. This method is a useful one, but it has some limitations. For example, the change of the position of halide, this is commonly axial with the pyranose ring to β-glycosyl halide. In addition, some spodric and limited direct methods for the said transformation are available in literature. However, few modifications have been reported by the activation of only acyclic organic alcohol using diphenyl phosphorazidate (DPPA) and 1,8-Diazabicyclo [5.4.0]undec-7-ene (DBU) (Lal, 1977) and the use of bis(p- nitrophenyl) phosphorazidate (Mizuno and Shioiri, 1997). Along this line, method based on the work of Danishefsky group (Chan et al., 2005) is widely applied. They successfully employed DPPA with other reagents to displace a benzyl alcohol in high yield. DPPA undergoes pseudohalogen replacement of the azide group by treatment with nucleophilic reagents, such as: butanol, water, ammonia, and various amines. Herein DPPA is used as an azide source in preparing some organic azide compounds. In addition, DBU is used in organic synthesis as a catalyst, non-nucleophilic base and also as complexing ligand. Researchers at Merck Research Laboratories developed a one-pot method to react a secondary alcohol with DPPA and DBU and that did not involve Mitsunobu conditions (Thompson et al., 1993), where