Sugar chain asparagine derivatives, sugar chain asparagine, sugar chain and processes for producing these

1. An asparagine-linked α2,3-oligosaccharide derivative having undeca- to hepta-saccharides containing fluorine and represented by the formula (1) given below

wherein R 1 and R 2 are each a hydrogen atom or one of the groups represented by the formulae (2) to (5) given below and may be the same or different, provided that one of R 1 and R 2 should always be the group of the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

2. An asparagine-linked α2,6-oligosaccharide derivative having undeca- to hepta-saccharides, containing fluorine and represented by the formula (6) given below

wherein R X and R Y are each a hydrogen atom, a group represented by the formula (7) given below or one of the groups represented by the formulae (3) to (5) given below, provided that one of R X and R Y should always be a group of the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.

3. An asparagine-linked α2,3-oligosaccharide having undeca- to hepta-saccharides containing fluorine and represented by the formula (8) given below

wherein R 1 and R 2 are each a hydrogen atom or one of the groups represented by the formulae (2) to (5) given below and may be the same or different, provided that one of R 1 and R 2 should always be the group of the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

4. An asparagine-linked α2,6-oligosaccharide having undeca- to hepta-saccharides, containing fluorine and represented by the formula (9) given below

wherein R X and R Y are each a hydrogen atom, a group represented by the formula (7) given below or one of the groups represented by the formulae (3) to (5) given below, provided that one of R X and R Y should always be a group of the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.

5. An α2,3-oligosaccharide having undeca- to hepta-saccharides containing fluorine and represented by the formula (10) given below

wherein R 1 and R 2 are each a hydrogen atom or one of the groups represented by the formulae (2) to (5) given below and may be the same or different, provided that one of R 1 and R 2 should always be the group of the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

6. An α2,6-oligosaccharide having undeca- to hepta-saccharides, containing fluorine and represented by the formula (11) given below

wherein R X and R Y are each a hydrogen atom, a group represented by the formula (7) given below or one of the groups represented by the formulae (3) to (5) given below, provided that one of R X and R Y should always be a group of the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.

7. A process for preparing an asparagine-linked α2,3-disialooligosaccharide derivative having undecasaccharide and represented by the formula (12) given below, the process comprising:

transferring sialic acid or a sialic acid derivative to an asparagine-linked oligosaccharide protected with a lipophilic protective group using a sialic acid transferase; and

subjecting the resulting asparagine-linked oligosaccharide protected with a lipophilic protective group to chromatography for separation

wherein R 1 and R 2 are each a group represented by the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH.

8. A process for preparing an asparagine-linked α2,3-monosialooligosaccharide derivative having decasaccharide, containing fluorine and represented by the formula (13) given below, the process comprising:

transferring sialic acid or a sialic acid derivative to an asparagine-linked oligosaccharide protected with a lipophilic protective group using a sialic acid transferase; and

subjecting the resulting asparagine-linked oligosaccharide protected with a lipophilic protective group to chromatography for separation

wherein one of R 1 and R 2 is a group represented by the formula (2), and the other thereof is a group represented by the formula (3)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

9. A process for preparing an asparagine-linked α2,6-disialooligosaccharide derivative having undecasaccharide, containing fluorine and represented by the formula (17) given below, the process comprising:

transferring sialic acid or a sialic acid derivative to an asparagine-linked oligosaccharide protected with a lipophilic protective group using a sialic acid transferase; and

subjecting the resulting asparagine-linked oligosaccharide protected with a lipophilic protective group to chromatography for separation

wherein R X and R Y are each a group represented by the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.

10. A process for preparing an asparagine-linked α2,6-monosialooligosaccharide derivative having decasaccharide, containing fluorine and represented by the formula (18) given below, the process comprising:

transferring sialic acid or a sialic acid derivative to an asparagine-linked oligosaccharide protected with a lipophilic protective group using a sialic acid transferase; and

subjecting the resulting asparagine-linked oligosaccharide protected with a lipophilic protective group to chromatography for separation

wherein one of R X and R Y is a group represented by the formula (7), and the other thereof is a group represented by the formula (3)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F;

11. A process for preparing an asparagine-linked α2,3-oligosaccharide having undeca- to hepta-saccharides, containing fluorine and represented by the formula (8)

the process comprising removing the protective group from an asparagine-linked α2,3-oligosaccharide derivative having undeca- to hepta-saccharides and represented by the formula (1)

wherein R 1 and R 2 are each a hydrogen atom or one of the groups represented by the formulae (2) to (5) given below and may be the same or different, provided that one of R 1 and R 2 should always be the group of the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

12. A process for preparing an asparagine-linked α2,6-oligosaccharide having undeca- to hepta-saccharides, containing fluorine and represented by the formula (9)

the process comprising removing the protective group from an asparagine-linked α2,6-oligosaccharide derivative having undeca- to hepta-saccharides and represented by the formula (6)

wherein R X and R Y are each a hydrogen atom, a group represented by the formula (7) given below or one of the groups represented by the formulae (3) to (5) given below, provided that one of R X and R Y should always be a group of the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.

13. A process for preparing an α2,3-oligosaccharide having undeca- to hepta-saccharides, containing fluorine and represented by the formula (10)

the process comprising removing the asparagine residue from an asparagine-linked α2,3-oligosaccharide having undeca- to hepta-saccharides and represented by the formula (8)

wherein R 1 and R 2 are each a hydrogen atom or one of the groups represented by the formulae (2) to (5) given below and may be the same or different, provided that one of R 1 and R 2 should always be the group of the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

14. A process for preparing an α2,6-oligosaccharide having undeca- to hepta-saccharides, containing flourine and represented by the formula (11)

the process comprising removing the asparagine residue from an asparagine-linked α2,6-oligosaccharide having undeca- to hepta-saccharides and represented by the formula (9)

wherein R X and R Y are each a hydrogen atom, a group represented by the formula (7) given below or one of the groups represented by the formulae (3) to (5) given below, provided that one of R X and R Y should always be a group of the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.

15. An asparagine-linked oligosaccharide derivative containing at least one fucose in N-acetylglucosamine on the nonreducing terminal side of the asparagine-linked α2,3-oligosaccharide derivative having undeca- to hepta-saccharides containing fluorine and represented by the formula (1) given below

wherein R 1 and R 2 are each a hydrogen atom or one of the groups represented by the formulae (2) to (5) given below and may be the same or different, provided that one of R 1 and R 2 should always be the group of the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

16. An asparagine-linked oligosaccharide derivative containing at least one fucose in N-acetylglucosamine on the nonreducing terminal side of the asparagine-linked α2,6-oligosaccharide derivative having undeca- to hepta-saccharides containing fluorine and represented by the formula (6) given below

wherein R X and R Y are each a hydrogen atom, a group represented by the formula (7) given below or one of the groups represented by the formulae (3) to (5) given below, provided that one of R X and R Y should always be a group of the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.

17. A process for preparing an asparagine-linked oligosaccharide derivative containing at least one fucose in N-acetylglucosamine on the nonreducing terminal side of an asparagine-linked oligosaccharide containing fluorine wherein the asparagine has amino group protected with a lipophilic protective group and represented by the formula (1) given below, the process comprising:

transferring fucose to the asparagine-linked oligosaccharide wherein the asparagine has the protected amino group with a lipophilic protective group using a fucose transferase; and

subjecting the resulting asparagine-linked oligosaccharide protected with the lipophilic protective group to chromatography for separation

wherein R 1 and R 2 are each a hydrogen atom or one of the groups represented by the formulae (2) to (5) given below and may be the same or different, provided that one of R 1 and R 2 should always be the group of the formula (2)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH;

(c) R=OH, R′=OH, R″=F; or

(d) R=OH, R′=OH, R″=OH;

18. A process for preparing an asparagine-linked oligosaccharide derivative containing at least one fucose in N-acetylglucosamine on the nonreducing terminal side of an asparagine-linked oligosaccharide containing fluorine wherein the asparagine has amino group protected with a lipophilic protective group and represented by the formula (6) given below, the process comprising:

transferring fucose to the asparagine-linked oligosaccharide wherein the asparagine has the protected amino group with a lipophilic protective group using a fucose transferase; and

subjecting the resulting asparagine-linked oligosaccharide protected with the lipophilic protective group to chromatography for separation

wherein R X and R Y are each a hydrogen atom, a group represented by the formula (7) or one of the groups represented by the formulae (3) to (5) given below, provided that one of R X and R Y should always be a group of the formula (7)

wherein R, R′ and R″ are in the following combinations:

(a) R=F, R′=OH, R″=OH;

(b) R=OH, R′=F, R″=OH; or

(c) R=OH, R′=OH, R″=F.