Sialic acid derivatives and process therefor

• US 4,990,603 A
• Filed: 06/30/1987
• Issued: 02/05/1991
• Est. Priority Date: 07/04/1986
• Status: Expired due to Fees

• Current Assignee: Mect Corp.
• Original Assignee: Mect Corp.
• Inventors: Sugimoto, Mamoru, Ito, Masayoshi, Yoshimura, Shoji, Ogawa, Tomoya, Numata, Masaaki, Shitori, Yoshiyasu
• Primary Examiner(s): Griffin, Ronald W.
• Assistant Examiner(s): White, Everett
• Application Number:
  US07/068,205
• Time in Patent Office: 1,316 Days
• Field of Search: 536/17.4, 536/17.2, 536/4.1, 536/18.5, 536/18.7, 536/22, 536/55.2, 536/55.3, 536/115, 536/119, 536/120
• US Class Current: 536/17.4
• CPC Class Codes: C07H 15/10 containing unsaturated carbon-to-carbon bonds
• CPC Class Codes: C07H 3/06 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages

Abstract

The present invention relates to sialic acid derivatives. According to the present invention, there is provided sialic acid derivatives having the general formula (I): ##STR1## wherein, R¹ represents hydrogen, an acetyl group, a trityl group, ##STR2## (R⁵ represents hydrogen or an acetyl group and R⁶ represents hydrogen, sodium or a methyl group).

R² represents hydrogen or an acetyl group,

one of R³ and R⁴ represents ##STR3## (R⁷ represents a hydrogen atom or an acetyl group, R⁸ represents a hydrogen atom, an acetyl group or a benzyl group, R⁹ represents a hydrogen atom, an acetyl group, a benzyl group or ##STR4## wherein R¹⁰ represents a hydrogen atom or a benzoyl group), while the other represents --COOR¹¹ wherein R¹¹ represents hydrogen, sodium, or a methyl group.

Claims

1. A process for producing ganglioside GD₃ having the general formulae (8) and (9):

##STR15## (a) deacetylating a compound (3) having the following formula (3);

##STR16## , to produce a compound (4) having the following formula (4);

##STR17## (b) tritylating said compound (4), to produce a compound (5) having the following formula (5);

##STR18## wherein Tr is a trityl group, (c) acetylating said compound (5), to produce a compound (6) having the following formula (6);

##STR19## wherein Tr is defined above, (d) detritylating said compound (6), to produce a compound (7) having the following formula (7);

##STR20## , and then (e) reacting said compound (7) with a compound (2) having the following formula (2);

##STR21##

2. A process for producing a compound (7) having the following formula (7):

##STR22## wherein ##STR23## is an OAc group and ##STR24## is an OBn group (Bn is a benzyl group), comprising;

(a) deallylating a compound (1) having the following formula (1);

##STR25## wherein ##STR26## is defined above, to produce a compound (2) having the following formula (2);

##STR27## wherein ##STR28## is defined above, (b) chlorinating said compound (2) to produce a compound (3) having the following formula (3);

##STR29## wherein ##STR30## is defined above, (c) reacting said compound (3) with benzyl lactose, to produce compounds (4) and (5) having the following formulae (4) and (5);

##STR31## wherein ##STR32## and ##STR33## are defined above, and then (d) acetylating said compound (5).

3. A process for producing a compound having the following formula (13):

##STR34## comprising;

(a) acetylating a compound (4) having the following formula (4);

##STR35## wherein ##STR36## is an OAc group and ##STR37## is an OBn group (Bn is a benzyl group), to produce a compound (6) having the following formula (6);

##STR38## wherein ##STR39## and ##STR40## are defined above, and then (b) debenzylating said compound (6), to produce a compound (8) having the following formula (8);

##STR41## wherein ##STR42## is defined above. (c) acetylating said compound (8), to produce a compound (9) having the following formula (9);

##STR43## wherein ##STR44## is defined above, (d) selectively deacetylating said compound (9), to produce a compound (10) having the following formula (10);

##STR45## wherein ##STR46## is defined above, (e) reacting said compound (10) with trichloroacetonitrile to produce a compound (11) having the following formula (11);

##STR47## wherein ##STR48## is defined above, (f) reacting said compound (11) with benzoylceramide, to produce a compound (12) having the following formula (12);

##STR49## wherein ##STR50## is defined above and Bz is a benzoyl group, and then (g) hydrolyzing said compound (12).

4. A process for producing a compound (7) having the following formula (7):

##STR51## wherein ##STR52## is an OAc group and ##STR53## is an OBn group (Bn is a benzyl group), comprising acetylating a compound (6) having the following formula (6);

##STR54## wherein ##STR55## and ##STR56## are defined above.

5. The process of claim 4, wherein said compound (6) is one of the compounds obtained by reacting benzyl lactose with a compound (3) or (4) having the following formula (3) or (4). ##STR57## wherein ##STR58## is an OAc group.

6. The process of claim 5, wherein said compound (4) is obtained by pyridylsulfidizing a compound (2) having the following formula (2):

##STR59## wherein ##STR60## is an OAc group.

7. A process for producing a compound (14) having the following formula (14):

##STR61## comprising;

(a) acetylating a compound (5) having the following formula (5);

##STR62## wherein ##STR63## is an OAc group and ##STR64## is an OBn group (Bn is a benzyl group), to produce a compound (8) having the following formula (8);

##STR65## wherein ##STR66## and ##STR67## are defined above, (b) debenzylating said compound (8), to produce a compound (9) having the following formula (9);

##STR68## wherein ##STR69## is defined above, (c) acetylating said compound (9), to produce a compound (10) having the following formula (10);

##STR70## wherein ##STR71## is defined above, (d) deacetylating said compound (10), to produce a compound (11) having the following formula (11);

##STR72## wherein ##STR73## is defined above, (e) reacting said compound (11) with Cl₃ CCN, to produce a compound (12) having the following formula (12);

##STR74## wherein ##STR75## is defined above, (f) reacting said compound (12) with benzoylceramide, to produce a compound (13) having the following formula (13);

##STR76## wherein ##STR77## is defined above, and then (g) deactylating, debenzylating and then saponifying said compound (13).

8. The process of claim 7, wherein said compound (5) is one of the compounds obtained by reacting benzyl lactose with a compound (3) or (4) having the following formula (3) or (4):

##STR78## wherein ##STR79## is an OAc group.

9. The process of claim 8, wherein said compound (4) is obtained by pyridylsulfidizing a compound (2) having the following formula (2):

##STR80## wherein ##STR81## is an OAc group.

10. A sialic acid derivative having the formula (I):

##STR82## wherein R¹ represents ##STR83## (R⁵ represents hydrogen or an acetyl group and R⁶ represents hydrogen, sodium or a methyl group)

R² represents hydrogen or an acetyl group,

one of R³ and R⁴ represents --OCH₂ CHCH₂, or ##STR84## while the other represents -COOR¹¹, wherein R¹¹ represents hydrogen, sodium or a methyl group.

11. A sialic acid derivative having the formula (I):

##STR85## wherein R¹ represents hydrogen, an acetyl group, a trityl group, ##STR86## (R⁵ represents hydrogen or an acetyl group and R⁶ represents hydrogen, sodium or a methyl group)

R² represents hydrogen or an acetyl group,

one of R³ and R⁴ represents ##STR87## (R⁷ represents hydrogen or an acetyl group, R⁸ represents hydrogen, an acetyl group or a benzyl group, R⁹ represents hydrogen, an acetyl group, a benzyl group or ##STR88## wherein R¹⁰ represents hydrogen or a benzoyl group), while the other represents -COOR¹¹ wherein R¹¹ represents hydrogen, sodium, or a methyl group.