Although a-d-Galp-(1^3)-|8-d-Galp-(1^4)-|6-d-Glc^ and a-d-Galp-(1^3)-^-d-Galp-(1^4)-^-d-GlcNAcp sequences had been synthesized chemically [90-94], these synthetic methods failed to produce a large quantity of oligosaccharides effectively. In addition to our successful efforts in the enzymatic synthesis of several a-gal oligosaccharides using a recombinant a1,3-GT, we have developed a practical and efficient route for chemical synthesis of derivatives of a-gal trisaccharide 2 on a 50 g scale. Synthesis of a-gal epitope derivatives 35 and 37 was achieved by utilizing a stereoselective and high-yielding glycosylation method, with the acceptor prepared through an efficient dibutylin oxide mediated regioselective protecting scheme . In preparation of the glycosylation acceptor 33 (Fig. 13), lactosyl bromide 29 was converted to azide 30  and then deacetylated to generate lactosyl azide 8. The regioselective monoalkylation of the C3 hydroxy group of galactose with p-methoxybenzyl chloride (MPMCl) was achieved through a one-pot reaction m i o
Compound a-D-Galp-( 1 —>3)-ß-D-Galp-( 1 ^-d-GIcNH^ (13)
a-D-Galp-( 1 —>3)-ß-D-Galp-(l -^4)-ß-D-GlcNH2p-(1^3)-ß-D-Galp-( 1^4)-ß-D-Glcp-N3 (28) a-D-Galp-(l—>3)-ß-D-Gal/>-(l—>4)-D-GlcNHAcp (11)
Figure 12 Comparing inhibitory activity of N-acetylated a-gal epitopes and those bearing a free amino group.
sequence involving a dibutylstannylene acetal intermediate. The selectively protected azide 31 was peracetylated to give compound 32, which was selectively deprotected at C3-OH through oxidative cleavage of the MPM ether with cerium(IV) ammonium nitrate (CAN)  to yield acceptor building block 33 (Fig. 13). Large scale (50 g) glycosylation between perbenzylated phenyl thiogalactoside donor 34  and acceptor 33 (Fig. 14) was carried out under activation of V-iodosuccinimide/triflic acid
Ac9 OAc .OAc NaN3, TBAHS AcO 0Ac .OAc
OAc OAc Br 95% OAc OAc
OAc Br 95%
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