In 1992 Feizi and co-workers reported that an equimolar mixture of sulfated Le x and Le a tetrasaccharides derived from an ovarian cystoadenoma glycoprotein were strongly bound to E-and L-selectins [1]. In a recent communication, they concluded that sulfated Le a tetrasaccharide [2] and pentasaccharide [3] emerge as the most potent E-selectin ligands so far studied [4]. Those observations prompted us to synthesize sulfated Le x and Le a pentaosyl ceramide.
In our preceding paper [5], we described the total synthesis of sulfated Le x pentaosyl ceramide. In connection with our project on the synthesis of glycosphingolipids, we herein deal with a stereocontrolled, facile, first total synthesis of sulfated Le a pentaosyl ceramide 1 for further chemical and biological scrutiny. The overall strategy is depicted in Scheme 1. Retrosynthetic analysis of a suitable route to 1 (Scheme 1) led us to design a putative glycosyl donor 2 that could be coupled with ceramide derivative 3 [6]. Donor 2 was expected to be constructed from synthons derived from D-galactose, 2-amino-2deoxy-D-glucose, L-fucose, and lactose (compounds 4-6 [7] and 7 [8], respectively, all of which are prepared from readily available compounds).
Glycosylation of 4 (1.5 equiv) with $ in dichloromethane in the presence of MeOTf at room temperature afforded an 89% yield of the desired /3-(1 ~ 3)-linked compound 8 {[a] D -20.9 ยฐ (c 1.0); Rf 0.38 (3:1 toluene-AcOEt)}, t The /3 configuration of 8 was assigned from the 1H NMR data that showed a signal for H-ld at 6H 4.547 (d, J = 8.5 * Corresponding author. 1 Optical rotations were determined for solutions in CHC13 at 25ยฐC. NMR spectra were recorded with a JNM-GX 500 Fourier-transform instrument. The values of ~H are expressed in ppm downfield from the signal for internal Me4Si for solutions in CDC13 at 24ยฐC, unless noted otherwise. Mass spectra were determined using electrospray-ionization (ESIMS) and fast-atom bombardment mass spectrometry (FABMS) techniques. Elsevier Science Ltd.