Efficient and Stereoselective Synthesis of α(2→9) Oligosialic Acids: From Monomers to Dodecamers

Abstract

The chain gang: The α(2→9) dodecasialic acid has been stereoselectively synthesized in 12 steps by using a convergent block synthesis (see scheme). The use of chloroacetyl protecting groups and a phosphate group as a leaving group led to the improvement of the α selectivity of the glycosylation reactions, thus allowing synthesis of oligomers.

Automated solid-phase synthesis of oligosaccharides containing sialic acids

“…Based on these considerations sialyl phosphate building blocks 4 and 5 [14] were selected for automated glycan assembly using monosaccharides (Scheme 1). The synthesis of building block 4 commenced with the placement of a C-9 Fmoc protecting group on thioglycoside 1 [14] to produce 2 .…”

“…The synthesis of building block 4 commenced with the placement of a C-9 Fmoc protecting group on thioglycoside 1 [14] to produce 2 . Installation of O -chloroacetyl groups on C-7 and C-8 for better α-stereoselectivity [12] produced 3 .…”

“…Installation of O -chloroacetyl groups on C-7 and C-8 for better α-stereoselectivity [12] produced 3 . An α-anomeric phosphate leaving group was chosen since it had previously shown high reactivity [14,18] and selectivity [15]. Building block 4 was obtained in 54% yield over three steps from 1 .…”

“…Monosaccharide building blocks 4 , 5 [14], 6 , 7 [21], 8 , 9 [21], and 10 [5] were employed for these syntheses. Merrifield polystyrene resin equipped with a photocleavable linker, 11 , was placed in the reaction chamber of the automated synthesizer and the coupling cycles were initiated following programmed maneuvers.…”

Sialoside Arrays: New Synthetic Strategies and Applications

“…Moreover, the RRvs of sialylated disaccharides can be programmed by manipulating the protecting groups of the second sugar residue at the reducing end and can be applied to the synthesis of α 2,3-linked sialylated pentasaccharide 4 (Scheme 1) [56]. More importantly, the phosphate donor can also be applied to the convergent block synthetic strategy to synthesize the various lengths of α 2,9-linked oligosialic acid up to dodecamer in good yield and alpha selectivity (Scheme 2) [72].…”