Synthesis of Sambubiose.

Total Synthesis of Natural Disaccharide Sambubiose

“…To date, to the best of our knowledge, only one synthesis of sambubiose has been reported [ 10 ]; however, the method followed by Erbing and Lindberg [ 10 ] ( Scheme 1 ) and subsequently applied by Dick et al [ 11 ] has several drawbacks and improvements could be made in the reagents and conditions.…”

“…Firstly, the purification of benzyl 3,5,6-tri- O -benzyl-α-D-glucofuranoside ( 4a ) to eliminate high-boiling benzyl alcohol from the reaction crude mixture was extremely difficult both by distillation and/or by chromatography. Erbing and Lindberg [ 10 ], therefore, had to employ acetylation and deacetylation as additional synthetic steps via benzyl 2- O -acetyl-3,5,6-tri- O -benzyl-α-D-glucofuranoside ( 3a ) to purify 4a ( Scheme 1 , “iii” and “iv” steps). Secondly, the use of the intrinsically unstable donor 2,3,4-tri- O -acetyl-α-D-xylopyranosyl bromide ( 5a ), which must be freshly prepared and recrystallized because of its low stability, even when refrigerated, was also problematic.…”

“…Secondly, the use of the intrinsically unstable donor 2,3,4-tri- O -acetyl-α-D-xylopyranosyl bromide ( 5a ), which must be freshly prepared and recrystallized because of its low stability, even when refrigerated, was also problematic. Moreover, Erbing and Lindberg [ 10 ] used a stoichiometric amount of mercuric cyanide as a glycosylation promoter. This reactant should not be used because of its high toxicity and dangerousness.…”

“…Furthermore, Hg(CN) 2 does not allow a stereospecific control of glycosylation: 6 [ 12 ] must be separated from its anomer since the output of the reaction is an α- and β-mixture. Finally, and importantly, the authors did not fully characterize the natural disaccharide sambubiose [ 10 ]. Hence, the aim of this investigation was to develop an improved efficient strategy to synthesize our target molecule overcoming the abovementioned drawbacks.…”

“…Herein, as a part of our ongoing investigations of disaccharide chemistry [ 13 , 14 , 15 , 16 ], we describe an efficient synthetic method that allowed us to obtain sambubiose in a satisfactory and higher overall yield than previously reported [ 10 ] as well as to achieve its full characterization. The proposed methodology ensured an effective stereospecific glycosylation control and exploited strategies of protection and deprotection of functional groups which also guide the regioselective reaction progress.…”