Synthesis of fragments of the capsular polysaccharide of Haemophilus influenzae type b. Part I. Preparation of suitably protected 1-O-β-d-ribofuranosyl-d-ribitol building blocks

Article abstract of DOI:10.1002/recl.19871060905

The synthesis of the protected ribosylribitol derivatives 15 and 17, which are building blocks for the preparation of fragments of the H. influenzae type b polysaccharide, is presented. Starting from d-ribonolactone (1), 5-O-allyl-2,3,4-tri-O-benzyl-d-ribitol (8) was prepared in seven steps (Scheme 1). Coupling of 8 with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose (9) in the presence of trimethylsilyl trifluoromethanesulfonate gave the ribosylribitol derivative 10 (Scheme 2), which was debenzoylated to afford compound 11. The C-3′- and C-5′-hydroxyl functions of the ribose moiety of 11 were protected with the 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl group and the C-2′ position with the benzyloxymethyl group. Compound 13 thus obtained was converted into its 5-O-trans-1-propenyl isomer 14. Cleavage of the propenyl group from 14 gave compound 15, which can be phosphorylated at O-5 of the ribitol. On the other hand, removal of the 3′,5′-protection from 14 and subsequent blocking of the primary hydroxyl function yielded ribosylribitol derivative 17 having a 3′-hydroxyl function available for phosphorylation.