SYNTHESIS OF 4 SPACER-CONTAINING TRISACCHARIDES WITH THE 4-O-(BETA-L-RHAMNOPYRANOSYL)-D-GLUCOPYRANOSE UNIT IN COMMON, REPRESENTING FRAGMENTS OF CAPSULAR POLYSACCHARIDES FROM STREPTOCOCCUS-PNEUMONIAE TYPE-2, TYPE-7F, TYPE-22F, AND TYPE-23F

The synthesis is reported of 3-aminopropyl 3-O-[4-O-(beta-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-alpha-L-rhamnopyranoside (34),3-aminopropyl 2-acetamido-3-O-[4-O-(beta-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-2-deoxy-beta-D-galactopyranoside (37), 3-aminopropyl 3-O-[4-O-(beta-L-rhamnopyranosyl)-alpha-D-glucopyranosyl]-alpha-D-galactofuranoside (41), and 3-aminopropyl 4-O-[4-O-(beta-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-beta-D-galactopyranoside (45). These are spacer-containing fragments of the capsular polysaccharides of Streptococcus pneumoniae type 2, 7F, 22F, and 23F, respectively, which are constituents of Pneumovax(C) 23. 2,3,4-Tri-O-benzyl-alpha-L-rhamnopyranosyl bromide was coupled to 1,6-anhydro-2,3-di-O-benzyl-beta-D-glucopyranose (3). Opening of the anhydro ring, removal of AcO-1, and imidation of 1,6-anhydro-2,3-di-O-benzyl-4-O-(2,3,4-tri-O-benzyl-beta-L-rhamnopyranosyl)-beta-D-glucopyranose (4-beta) afforded 6-O-acetyl-2,3-di-O-benzyl-4-O-(2,3,4-tri-O-benzyl-beta-L-rhamnopyranosyl)-alpha-beta-D-glucopyranosyl trichloroacetimidate (7-alpha-beta). Condensation of 7-alpha-beta with 3-N-benzyloxycarbonylaminopropyl 2-O-benzyl-5,6-O-isopropylidene-alpha-D-galactofuranoside (26), followed by deprotection gave 41. Opening of the anhydro ring of 4-beta followed by debenzylation, acetylation, removal of AcO-1, and imidation yielded 2,3,6-tri-O-acetyl-4-O-(2,3,4-tri-O-acetyl-beta-L-rhamnopyranosyl)-alpha-D-glucopyranosyl trichloroacetimidate (11). Condensation of 11 with 3-N-benzyloxycarbonylaminopropyl 2,4-di-O-benzyl-alpha-L-rhamnopyranoside (18), with 3-N-benzyloxycarbonylaminopropyl 2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-galactopyranoside (21), or with 3-N-benzyloxycarbonylaminopropyl 2-O-acetyl-3-O-allyl-6-O-benzyl-beta-D-galactopyranoside (31), followed by deprotection afforded 34, 37, and 45, respectively.