www.elsevier.nl/locate/carres Carbohydrate Research 328 (2000) 61 – 69 Selective formation of C-2 azidodeoxy-D-glucose derivatives from D-glucal precursors using the azidonitration reaction Peter H. Seeberger a, *, Susanne Roehrig a , Peter Schell a , Yuan Wang b , William J. Christ b a Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 -4307, USA b Eisai Research Institute, 4 Corporate Drie, Andoer, MA 01810, USA Received 10 August 1999; accepted 7 April 2000 Abstract A series of glucals, protected by cyclic acetal protecting groups to conformationally constrain the C-4 and C-6 hydroxyl groups, were subjected to the azidonitration reaction to furnish the corresponding C-2 azidodeoxy-D-glu- coses. 4,6-O -Isopropylidene-3-O -triisopropylsilyl-D-arabino -hex-1-enitol afforded 2-azido-2-deoxy-4,6-O -isopropyli- dene-3-O -triisopropylsilyl-D-glucopyranosyl nitrate and its D-manno isomer in a 20:1 ratio. These findings allow the azidonitration reaction to be now used for the preparation of a variety of glucosamine building blocks from differentially protected glucal precursors. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: Azidonitration; Glucals; Conformational restriction; 2-Amino-2-deoxy-D-glycosides 1. Introduction The realization that complex carbohydrates are involved in many biologically important signal transduction processes has led to in- creased interest in the development of novel strategies for the synthesis of these biopoly- mers [1]. 2-Amino-2-deoxy glycosides are fre- quently encountered constituents of many naturally occurring glycoconjugates. Some methods for the introduction of a C-2 azido functionality rely upon the conversion of the free amino group to the corresponding azide by diazotransfer [2], while others are based on the displacement of other C-2 alkylsulfonyl groups [3,4]. Additional protocols rely on the installation of a C-2 azide from glycal precur- sors. The conversion of glycals into 2-azido-2- deoxyglycosyl nitrates that function as 2-amino-2-deoxy glycoside precursors is com- monly effected by the azidonitration reaction that was developed by Lemieux and Ratcliffe in 1979 [5]. The anomeric nitrate group can be readily converted into a hydroxyl [6], halide [5,7], or acetyl functionality [8] and allows for access to a variety of glycosyl donors contain- ing a nonparticipating 2-azido group. Reac- tion of protected D-galactal 1 with ceric ammonium nitrate (CAN) and sodium azide results in the formation of a mixture of anomers of the desired 2-azido-2-deoxy-D- galactose derivative 2 as well as varying amounts of D-talose side product 3 containing the axial 2-azido moiety (Scheme 1) [5]. The azidonitration reaction is presumably initiated by the addition of an azide radical and pro- * Corresponding author. Fax: +1-617-2537929. E -mail address: seeberg@mit.edu (P.H. Seeberger). 0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0008-6215(00)00111-7