The synthesis of the monomeric fragment of the Haemophilus injluettzae type b (HIb) polysaccharide starting from orthoacetate I. is described. The construction of the dimer is also reported. The poly-(ribosyl-ribitol-phosphate) (PRP) 1. capsular polysaccharide isolated from the Haemophilus inj7uenzae type b bacteria has recently generated interest because of its possible use as a vaccine for infantile meningitis caused by the HJb bacteria'.
Recently Van Boom et al2 reported the synthesis of dimeric and trimeric fragments of PRP. The trimeric PRP attached to the carrier protein via a glycinarnide linker was found to elicit a promising immunogenic response. Soon after our laboratory reported a somewhat similar approach to a tetrameric PRP fragment with a linker derived from a representative part of the polysaccharide itselfg.
Both approaches had some common features. The ribosyl-ribitol moeity was constructed by a Koenigs-Knorr glycosidation of ribose tetraacetate with a suitably protected ribitol. After hydrolysis of the acetate groups, the resulting trio1 was differentiated by the use of Markiewicz's protecting group4 to simultaneously mask the 3' and 5' hydmxy functions. The 2'-hydmxyl was then benzyloxymethylated ; desilylation followed by selective protection of the primary hydroxyl group gave the required free 3'-hydmxyl which could then be coupled with the 5-OH of another ribosyl-ribitol unit through a phosphate moeity.
We now wish to report a new synthesis of the ribosyl-ribitol unit starting with the orthoacetate 2 as key intermediate since we believe it offers several advantages over the reported syntheses. The ortboester 1 has a dual purpose; it allows the simultaneous blocking of the 1' and 2' hydroxy groups thus effectively distinguishing between the 2' and 3' hydroxy groups. It can then be readily transformed to a l'-chlororiboside by the action of chlorotrimethylsilane5. Our sequence also keeps protecting group manipulations on the ribosyl-ribitol unit to a minimum. Furthermore any non-participating hydroxy groups can be benzylated thus simplyfying the &protection