Rhamnogalacturonan II: Chemical Synthesis of a Substructure Including α‐2,3‐Linked Kdo**

Abstract

The synthesis of a fully deprotected Kdo-containing rhamnogalacturonan II pentasaccharide is described. The strategy relies on the preparation of a suitably protected homogalacturonan tetrasaccharide backbone, through a post-glycosylation oxidation approach, and its stereoselective glycosylation with a Kdo fluoride donor.

Advances in glycoside and oligosaccharide synthesis

“…These stability issues can sometimes necessitate the use of non-homogeneous/impure compounds, with the exception of glycosyl fluorides, that are more stable to heat, less sensitive to hydrolysis and can often be purified by chromatography. [306][307][308][309] Initially, glycosyl fluorides were thought to be too stable for glycosylation reactions due to the large bond-dissociation energy of the C-F bond (552 kJ mol À1 ) but this has been found not to be the case. 296 The reactivity trend of the glycosyl halides is the inverse to their stability (I 4 Br 4 Cl 4 F) with protecting groups exerting Scheme 6 Utility of the Fischer-Helferich method in the synthesis of UDP-galactofuranose.…”

“…These stability issues can sometimes necessitate the use of non-homogeneous/impure compounds, with the exception of glycosyl fluorides, that are more stable to heat, less sensitive to hydrolysis and can often be purified by chromatography. 306–309 Initially, glycosyl fluorides were thought to be too stable for glycosylation reactions due to the large bond-dissociation energy of the C–F bond (552 kJ mol −1 ) but this has been found not to be the case. 296…”

“…Glycosyl fluorides have been used in the synthesis of portions of rhamnogalacturonan-II that contain 3-deoxy- d -manno-oct-2-ulosonic acid (Kdo) branches. 307 Different Kdo-glycosyl fluoride were iteratively tested with the glycosyl acceptor at different temperatures, promoters and glycosyl donor protecting group patterns. Addition of one equivalent of BF 3 ·Et 2 O every three hours at −40 °C proved be best to suppress donor elimination and minimize acetal protecting group cleavage.…”

“…Activation of glycosyl imidates using boron trifluoride etherate starting at −40 °C and raising slowly to room temperature in dichloromethane is a popular set of conditions shown to be suitable to synthesise a range of glycosides. 307 When neighbouring groups such as 2- O -benzoyl esters are present, the expected 1,2- trans products are obtained. With the non-participating protecting groups, e.g.…”

“…Anomeric halides have been employed in the synthesis of a wide range of complex glycans and glycoconjugates 307,[310][311][312][313][314][315][316][317] as well as AGA of mannan polysaccharides (Scheme 7), rhamnogalacturonan-II (Scheme 8) and Mycobacterium tuberculosis cell wall a-glucans (Fig. 13).…”