u 01

Scheme 10 Deprotection of the HA tetrasaccharide with N-acetylglucosamine at the reducing end.

methylsilyl triflate promoted glycosylation of II.25 with donor II.21 gave the tetrasaccharide II.26 in 87% yield. Following hydrolysis of the isopropylidene and acet-ylation, removal of both levulinoyl groups furnished diol II.27. Oxidation of the primary alcohols to the corresponding diacid II.28 was achieved in two steps in 86% overall yield. Finally, deacylation of II.28 with methylamine in methanol followed by selective N-acetylation afforded the target tetrasaccharide II.20 in 82% yield over the two steps.

Ogawa and coworkers also reported the synthesis of the corresponding HA tetrasaccharide having a glucuronic acid at the reducing end [50]. The strategy employed the prior formation of two ^(1,4)-linked disaccharides, followed by coupling of these disaccharides through the ^(1,3)-linkage to produce the target tetrasaccha-ride. The synthesis describes the preparation of two separate, orthogonally protected disaccharide units and highlights the use of Schmidt's trichloroacetimidate glyco-sylation methodology.

Construction of the target tetrasaccharide utilized the monomer units II.29 [51], II.30 [19], and II.31 (Scheme 11) [52]. Stereocontrolled glycosylation of II.30 with II.29 in the presence of boron trifluoride etherate (BF3-Et2O) afforded the corresponding disaccharide II.32 in 81% yield. Subsequent conversion of the methoxy-

Scheme 11 The Ogawa synthesis of the HA tetrasaccharide with glucuronic acid at the reducing end.

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