Oligosaccharide analytical standards

Patent metadata

Field	Value
Publication number	US-11780872-B2
Application number	US-202017116706-A
Country	US
Kind code	B2
Filing date	Dec 9, 2020
Priority date	Dec 9, 2019
Publication date	Oct 10, 2023
Grant date	Oct 10, 2023

Abstract

Disclosed herein are oligosaccharides and intermediates useful for the production thereof. The compounds are useful as analytical standards and as intermediates for the preparation of more complex oligosaccharide and N-glycan products. The compounds may be prepared in high purity using the selective stop/go synthetic methods disclosed herein.

First claim

What is claimed is:

1. A compound having the formula:

or a salt thereof, wherein
R MG2 is H or has the structure:

wherein R 5 is N 3 or NR 5a R 5b , wherein R 5a and R 5b are the same or different, and are H or Z—X 5 wherein Z is null, C═O, or SO 2 , and X 5 is C 1-4 alkyl, O—C 1-4 alkyl, C 1-4 haloalkyl, 0-C 1-4 haloalkyl, C 1-4 alkylaryl, O—C 1-4 alkylaryl, aryl, or O-aryl; or R 5a and R 5b can together form a ring; or R 5 is a radical having the formula:

wherein one or both of R 5c or R 5d constitute a conjugated payload;
R MG3 is H or has the structure:

wherein R 11 is N 3 , or NR 11a R 11b , wherein R 11a and R 11b are the same or different, and are H or Z—X 11 wherein Z is null, C═O, or SO 2 , and X 11 is C 1-4 alkyl, O—C 1-4 alkyl, C 1-4 haloalkyl, O—C 1-4 haloalkyl, C 1-4 alkylaryl, O—C 1-4 alkylaryl, aryl, O-aryl; or R 11a and R 11b can together form a ring; or R 11 can be a radical having the formula:

wherein one or both of R 11c or R 11d constitute a conjugated payload;
R MG4 is H or has the structure:

wherein R 9 is N 3 , or NR 9a R 9b , wherein R 9a and R 9b are the same or different, and are H or Z—X 9 wherein Z is null, C═O, or SO 2 , and X 9 is C 1-4 alkyl, O—C 1-4 alkyl, C 1-4 haloalkyl, O—C 1-4 haloalkyl, C 1-4 alkylaryl, O—C 1-4 alkylaryl, aryl, O-aryl; or R 9a and R 9b can together form a ring; or R 9 can be a radical having the formula:

wherein one or both of R 9c or R 9d constitute a conjugated payload;
R MG5 is H or has the structure:

wherein R 10 is N 3 or NR 10a R 10b , wherein R 10a and R 10b are the same or different, and are H or Z—X 10 wherein Z is null, C═O, or SO 2 , and X 10 is C 1-4 alkyl, O—C 1-4 alkyl, C 1-4 haloalkyl, O—C 1-4 haloalkyl, C 1-4 alkylaryl, O—C 1-4 alkylaryl, aryl, or O-aryl; or R 10a and R 10b can together form a ring; or R 10 can be a radical having the formula:

wherein one or both of R 10c or R 10d constitute a conjugated payload;
R 12 is hydrogen or a residue having the formula:

wherein R 13 is hydrogen or a residue having the formula:

wherein R 13b is selected from H and a conjugated cargo moiety, and R 13a is selected from OH and a conjugated cargo moiety;
R 14 is hydrogen or a residue having the formula:

wherein R 14b is selected from H and a conjugated cargo moiety, and R 14a is selected from OH and a conjugated cargo moiety;
R 1 is OH, or a residue having the formula:

R oz is H, C 1-4 alkyl, aryl, CF 3 , or CCl 3 ,
n is 1 or 0;
R fa is H or a fucose residue having the structure:

R 2 is OR c , NR 2n OR c , or NR 2n R c ; and R 3 is OR c or R c ;
wherein:
R 2n is H or C 1-4 alkyl;
R c is X p H, X p C 1-8 alkyl, X p C 1-8 alkylaryl, X p aryl, X p fluorescent marker, or an amino acid residue having the formula:

wherein R aa1 and R aa2 are selected from H, protecting group and additional amino acid residues;
R 3 is X p C 1-8 alkyl, X p C 1-8 alkylaryl, or X p aryl;
wherein X p is null or (CH 2 CH 2 O) z , wherein z is 1-500;
R 4 is N 3 , or NR 4a R 4b ,
wherein:
R 4a and R 4b are the same or different, and are H or Z—X 4 wherein Z is null, C═O, or SO 2 , and X 4 is C 1-4 alkyl, O—C 1-4 alkyl, C 1-4 haloalkyl, O—C 1-4 haloalkyl, C 1-4 alkylaryl, O—C 1-4 alkylaryl, aryl, or O-aryl; or R 4a and R 4b can together form a ring; or R 4 is a radical having the formula:

wherein one or both of R 4c or R 4d constitute a conjugated payload.

2. The compound according to claim 1 , wherein R 1 is a residue having the formula:

R c is an amino acid residue having the formula:

and
R aa1 and R aa2 are independently selected from H and Z a —X a wherein Z a is null, C═O, SO 2 , and X a can be C 1-4 alkyl, O—C 1-4 alkyl, C 1-4 haloalkyl, O—C 1-4 haloalkyl, C 1-4 alkylaryl, O—C 1-4 alkylaryl, aryl, or O-aryl.

3. The compound according to claim 2 , wherein R aa1 is Cbz (carboxybenzyl ether), and R aa2 is H.

4. The compound according to claim 1 , wherein R 1 has formula:

5. The compound according to claim 1 , wherein R 1 is a residue having the formula:

6. The compound according to claim 5 , wherein R 1 is a residue having the formula:

 wherein R c has the formula —(CH 2 ) nc R im , wherein nc is an integer from 1-8, and R im is —NH 2 , —SH, —OH, —COOH, —N 3 , C≡CH, a Michael acceptor, SO 3 , OSO 3 , or a biotin residue having the formula:

wherein X bt is selected from null, O, NH, or S.

7. The compound according to claim 5 , wherein R c is selected from coumarins, rhodamines, fluoresceins, cyanines, eosins, and erythrosins.

8. The compound according to claim 5 , wherein R c is a C 1-8 alkylaryl or aryl.

9. The compound according to claim 5 , wherein R c is a group having the formula:

wherein np is from 0-50, ns is from 2-7, and ns′ is from 2-5.

10. The compound according to claim 1 , wherein R MG2 , R MG3 , R MG4 and R MG5 are each hydrogen.

11. The compound according to claim 1 , having the formula:

Assignees

• Univ Georgia

Inventors

• Boons Geert-Jan
• Prudden Anthony Robert
• Liu Lin

Classifications

• C07H5/06 Primary

  Aminosugars · CPC title

• C12P19/26

  Preparation of nitrogen-containing carbohydrates · CPC title

• C12P19/305

  Pyrimidine nucleotides · CPC title

• C12P19/00

  Preparation of compounds containing saccharide radicals (ketoaldonic acids C12P7/58) · CPC title

• C12P19/18

  produced by the action of a glycosyl transferase, e.g. alpha-, beta- or gamma-cyclodextrins · CPC title