Studies towards a Conjugate Vaccine for Anthrax: Synthesis of the Tetrasaccharide Side Chain of the Bacillus anthracis Exosporium

The first synthesis of β‐L‐glycoside 17 of the tetrasaccharide β‐Ant‐(1 → 3)‐α‐L‐Rhap‐(1 → 3)‐α‐L‐Rhap‐(1 → 2)‐L‐Rhap is described (Schemes 1–3). Its spacer can be functionalized to make it amenable to conjugation to proteins by different conjugation methods. The synthesis was performed in a stepwise manner starting from the aglycon‐bearing terminal saccharide with thioglycosides as glycosyl donors. To attach the upstream terminal anthrose residue, the assembled linker‐equipped trisaccharide was glycosylated with ethyl 4‐azido‐3‐O‐benzyl‐2‐O‐(bromoacetyl)‐4,6‐dideoxy‐1‐thio‐β‐D‐glucopyranoside (11). Further functionalization of the tetrasaccharide thus obtained, followed by deprotection gave the target substance 17. Synthesis of substructures of 17 equipped with the same spacer, namely β‐L‐Rhap‐1‐O‐(CH2)5COOMe (21), α‐L‐Rhap‐(1 → 2)‐β‐L‐Rhap‐1‐O‐(CH2)5COOMe (22), and α‐L‐Rhap‐(1 → 3)‐α‐L‐Rhap‐(1 → 2)‐β‐L‐Rhap‐1‐O‐(CH2)5COOMe (23), is also described (Scheme 4).