De Novo Synthesis of a Methylene-Bridged Neu5Ac-α-(2,3)-Gal C-Disaccharide

Abstract

A general strategy toward the synthesis of C-ketosides of N-acetylneuraminic acid (Neu5Ac) has been developed and successfully applied to the synthesis of methylene-bridged Neu5Ac-alpha-(2,3)-Gal C-disaccharide 2. The key strategic element of this novel approach is a stereoselective, 6-exo-trig selective, electrophilic cyclization of the appropriate open chain precursor 4 by means of phenylselenyl triflate. The open chain precursor was formed by the addition of lithiated iodide 18 accessible from D-galactose to open chain aldehyde 5a obtained from D-glucono-delta-lactone by chain elongation. Subsequent C1-incorporation using Tebbe-reagent, formation of a cyclic carbonate, and deprotection of the two isopropylidene ketals afforded tetrol 4 which, upon treatment with phenylselenyl triflate, was stereoselectively cyclized in a 6-exo-trig selective manner. A selena-Pummerer rearrangement, oxidation, and esterification readily led to methyl ester 37 which, after deacetylation, could be regioselectively tetrabenzoylated with benzoyl cyanide. Triflate activation of the axial hydroxyl group in 40 and nucleophilic displacement by azide ion with inversion of configuration afforded azide 41, which was reduced with hydrogen and Pearlman's catalyst. Concomitant removal of the benzyl ethers and subsequent saponification of all ester moieties successfully completed the de novo synthesis of the desired methylene bridged Neu5Ac-alpha-(2,3)-Gal C-disaccharide 2.

Direct Carbonation of Glycerol with CO2 Catalyzed by Metal Oxides

“…[9,[12][13][14][15] The processo fo btaining cyclic carbonates via the direct reaction between glycols and CO 2 is more sustainable and ecological than the reactionw ith epoxides or use of phosgene (COCl 2 ). [16][17][18] However,t his route has thermodynamic limitations and the yields are usually low if water suppressor agents are not used to shift equilibrium. [19] We have shown that NaY zeolite impregnated with Ag, Zn and Sn oxidesa re good catalysts for the direct carbonation of glycerolt og lycerol carbonate.…”

Chemical approach for the syntheses of GM4 isomers with sialic acid to non-natural linkage positions on galactose

“…The ability of synthetic chemists to construct desired glycoside bonds has progressed and has contributed to our understanding of the recognition mechanisms for receptor proteins and the development of enzyme inhibitors. [7][8][9][10] Sialylation is one of the most challenging reactions in carbohydrate chemistry and often proceeds with low yield and poor stereoselectivity. [11][12][13] In particular, the stereoselective synthesis of a-sialosides is complicated because sialic acid does not contain a neighboring C-3 functional group to direct the stereochemical outcome of the glycosylation.…”

A strategy for constructing C-sialosides based on Ireland-Claisen rearrangement and its application for synthesis of CF2-linked ganglioside GM4 analog

“…Linhardt et al reported a convergent synthesis of CH(OH)-linked α(2,3)sialylgalactose 18 via SmI 2 -mediated coupling reaction [16] (Scheme 2). Schmidt et al reported a synthesis of CH 2 -linked α(2,3)sialylgalactose 19 via a linear synthetic sequence [17]. Since 18 was preparable very efficiently, we first planned to convert 18 into 21, and ketone 20 was prepared from alcohol 18 (Scheme 1).…”