US 12,173,024 B2
Method for synthesizing O-antigen saccharide chain of Helicobacter pylori serotype O:6
Jian Yin, Wuxi (CN); Jing Hu, Wuxi (CN); and Guangzong Tian, Wuxi (CN)
Assigned to Jiangnan University, Wuxi (CN)
Filed by Jian Yin, Wuxi (CN); Jing Hu, Wuxi (CN); and Guangzong Tian, Wuxi (CN)
Filed on Apr. 2, 2021, as Appl. No. 17/221,724.
Application 17/221,724 is a continuation of application No. PCT/CN2019/091198, filed on Jun. 14, 2019.
Claims priority of application No. 201910156533.1 (CN), filed on Mar. 1, 2019.
Prior Publication US 2021/0309683 A1, Oct. 7, 2021
Int. Cl. C07H 15/04 (2006.01); A61K 39/385 (2006.01); C07H 1/00 (2006.01); C08B 37/00 (2006.01); A61K 39/00 (2006.01)
CPC C07H 15/04 (2013.01) [A61K 39/385 (2013.01); C07H 1/00 (2013.01); C08B 37/00 (2013.01); A61K 2039/6031 (2013.01)] 10 Claims
 
1. A process of the preparation of compound(28) of the following formula:

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry
2) synthesizing a trisaccharide compound (11) by a deprotection reaction and a coupling reaction following the synthetic route below:

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry
4) synthesizing a pentasaccharide compound (16) by a first and a second coupling reactions following the synthetic route below:

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
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).