Synthesis of fragments of the capsular polysaccharide of <i>Haemophilus influenzae</i> type b: Part I. Preparation of suitably protected 1‐O‐β‐<i>D</i>‐ribofuranosyl‐<i>D</i>‐ribitol building blocks

Abstract

Abstract 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.