Method for synthesizing O-antigen saccharide chain of Helicobacter pylori serotype O:6

A process of the preparation of compound(28) of the following formula:

• wherein PG1, PG2, PG3, PG4, PG5, PG6, PG7 PG8, PG9, PG10, PG11, PG12, PG13a PG14, PG15, PG18, PG19, PG21, PG23, PG25, PG26, PG27, PG28, PG29 and PG30 are independently selected from the group consisting of hydrogen, acyl, 2-naphthylmethyl and its derivatives, benzyl and its derivatives, allyl and silyl;
• PG16 and PG24 are independently selected from the group consisting of hydrogen, alkoxycarbonyl and alkoxycarbonyl(acyl);
• PG20 is selected from the group consisting of alkanoyl, diformyl, carbobenzyloxy(Cbz) and its derivatives;
• the leaving groups LG are independently selected from the group consisting of halogen, iminoester group, thio group and phosphonic acid group;
• wherein the linker is an amino linker —(CH2)n—N—Y1Y2, wherein n=2-40, Y1 is H or benzyl (Bn), and Y2 is H or Cbz;
• and said process comprising:
• 1) synthesizing a disaccharide compound (9) by coupling a compound (1) as a glycosyl donor and a compound (8) as a glycosyl receptor in an organic solvent following the synthetic route below:
• 2) synthesizing a trisaccharide compound (11) by a deprotection reaction and a coupling reaction following the synthetic route below:
• wherein the deprotection reaction is performed by removing PG1 protection group on the compound (9) to make a compound (10);
• and
• wherein the coupling reaction is performed by coupling a compound (2) as a glycosyl donor and the compound (10) as a glycosyl receptor under Lewis acid catalysis to make the compound (11);
• 3) synthesizing a tetrasaccharide compound (13) by coupling a compound (3) as a glycosyl donor and a compound (12) as a glycosyl receptor in an organic solvent to make the compound (13) following the synthetic route below:
• 4) synthesizing a pentasaccharide compound (16) by a first and a second coupling reactions following the synthetic route below:
• wherein the first coupling reaction is performed by coupling the compound (3) as a glycosyl donor to a compound (14) as a glycosyl receptor in an organic solvent to make a compound (15);
• and
• wherein the second coupling reaction is performed by coupling the compound (15) as a glycosyl donor to the compound (12) as a glycosyl receptor in an organic solvent to make the compound (16);
• 5) synthesizing an octasaccharide compound (20) by a third and a fourth coupling reactions following the synthetic route below:
• wherein the third coupling reaction is performed by coupling the compound (3) as a glycosyl donor to a compound (17) as a glycosyl receptor in an organic solvent to make a compound (18);
• and
• wherein the fourth coupling reaction is performed by coupling the compound (18) as a glycosyl donor to a compound (19) as a glycosyl receptor in an organic solvent to make the compound (20);
• 6) synthesizing a trisaccharide compound (24) by a fifth and a sixth coupling reactions following the synthetic route below:
• wherein the fifth coupling reaction is performed by coupling a compound (6) as a glycosyl donor to a compound (21) as a glycosyl receptor in an organic solvent to make a compound (22);
• and
• wherein the sixth coupling reaction is performed by coupling the compound (22) as a glycosyl donor to a compound (23) as a glycosyl receptor in an organic solvent to make the compound (24);
• and
• 7) synthesizing the compound (28) following the synthetic route below:
• wherein the compound (24) as a glycosyl donor is coupled to a compound (25) as a glycosyl receptor under Lewis acid catalysis to obtain a compound (26);
• wherein protection groups PG21 and PG24 are selectively removed from the compound (26) to obtain a compound (27);
• and
• wherein the compound (7) as a glycosyl donor is coupled to the compound (27) as a glycosyl receptor under Lewis acid catalysis to make the compound (28).