Synthesis of Fragments of the Capsular Polysaccharide of Haemophilus Influnzae Type B Part II. Preparation and Structural Analysis of Fragments Comprising two and Three Repeating Units

Abstract

Abstract The synthesis of spacer-containing fragments of the capsular poly-saccharide of H. influenzas, comprising two and three repeating units (9a and 9b, respectively), is presented. Ribosylribitol building blocks 1 and 2 were coupled with bis [1-benzotriazolyl]-2-chlorophenyl phosphate (3) to give the phosphotriester derivative 5a (72%), which was selectively deprotected at O-5 of the terminal ribitol residue (cleavage of the trans-1-propenyl ether) to afford compound 6a (82%). Repeated coupling of building block 2 with 6a (chain elongation), followed by propenyl- cleavage, gave analogue 6b. Both derivatives 6a and 6b were coupled with spacer 7 (chain termination). The fully protected fragments 8a (84%) and 8b (49%, starting from 6a) were thus obtained. Complete deprotection of 8a and 8b was achieved in three steps. After purification and cation-exchange, 9a and 9b were obtained in 41 and 68% yields, respectively. The structural integrity of the largest fragment (9b) was confirmed by FAB MS and various NMR spectroscopic techniques.