Methyl 2-deoxy-2-[(1S)-2,5-dideoxy-2,5-imino-l-ribitol-1-C-yl)-a-d-glucopyranoside (()-6) was obtained from the product of Nozaki-Kishi coupling of 2,5-{[(tert-butoxy)carbonyl]imino}-2,5-dideoxy-3,4-O-isopropylidene-l-ribose ((À)-9) and 4
12). The alkenyl triflate ()-12 was derived from levoglucosenone (1). Introduction. ± Carbohydrate mimics are potentially useful molecular tools for biology [1] and may become leads for drug discovery [2]. In particular, C-linked disaccharides and oligosaccharides containing them offer the advantage of being resistant to acidic and enzymatic hydrolysis [3]. They are potential inhibitors of glycosidases and glycosyltransferases [4] [5] and potential antibacterial, antiviral, antimetastatic, antidiabetes, antihyperglycemic, antiadhesive, and immunostimulatory agents [6] [7]. A new class of selective glycosidase inhibitors has emerged, namely Clinked iminodisaccharides (aza-C-disaccharides) [8] [9], which contain not only the steric and charge information of the glycosyl moiety liberated during the enzymecatalyzed hydrolysis, but also that of the aglycon. The first example of a C-linked iminodisaccharide (1,5-dideoxy-1,5-imino-d-mannitol linked at C(6) of d-galactose through a CH 2 unit) was prepared by Johnson et al. [10]. Other examples of -linear× Clinked iminodisaccharides were obtained by the groups of Martin et al. [11] and van Boom and co-workers [12]. We have prepared the first examples of -branched× disaccharides [8] [13]. Further examples were reported by Johnson et al. [9] and by our group [14] [15]. Brandi and co-workers [16] have obtained the first examples of (1 3 2)linked pseudo imino-C-disaccharides in which pyrrolidine-2,3-diol or a pyrrolidin-2-ol is linked at C(2) of d-glucose via a CÀC bond.
In a preliminary report [17], our group had shown that (1 3 2)-C-linked disaccharides can be obtained applying the Nozaki-Kishi coupling reaction to triflate 2 (derived in two steps from levoglucosenone 1 [18]) and aldehyde 3 (derived from (4R)-4-hydroxy-l-proline). This generated allylic alcohol 4 (48%) that was converted (Scheme 1) to the imino-C-disaccharide 5. We have now applied this method to the preparation of the new C-linked iminodisaccharide ()-6 in which a pyrrolidine-3,4diol moiety is attached at C(2) of methyl a-d-glucopyranoside through a hydroxymethylene linker. As we shall see, the Nozaki-Kishi coupling was more difficult in this case and required a monocyclic alkenyl triflate rather than the bicyclic triflate 2 for a reasonable yield of condensation. Futhermore, the diastereoselectivity of the coupling was opposite to that reported with 2 3 3 4 [17].