Triazole linked carbohydrates

Details Triazole linked carbohydrates Triazole linked carbohydrates

2000-08-31

2003-12-16

Celsa, Bennett (Department: 1639)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S255000, C536S017200

Reexamination Certificate

active

06664399

ABSTRACT:

FIELD OF THE INVENTION
This invention concerns triazolyloligosaccharides, compounds having more than one oligosaccharide wherein the bonding between the oligosaccharide groups is a triazole group. Further disclosed is a process for the preparation of these triazolyloligosaccharides, the use of the compounds as potential enzyme inhibitors, and acetylenic intermediate compounds.
TECHNICAL BACKGROUND OF THE INVENTION
Host cell surface oligosaccharides serve as receptor ligands for protein molecules such as enzymes, antibodies and lectins, and they initiate many critical biological reactions. Unfortunately, these receptor ligands also initiate many harmful biological reactions by providing attachment sites for viruses, toxins, bacteria, etc.
Normally in an oligosaccharide, the constituent monosaccharide groups are linked by ether oxygen linkages. This ether oxygen linkage is difficult to construct chemically. Linking methods are specific for each sugar employed. The ether oxygen linking group is susceptible to hydrolysis by glycosyl hydrolases and non-enzymatic chemical hydrolysis. This ease of hydrolysis makes it difficult to use carbohydrate structures as pharmaceuticals. Further, there are no known methods of automated syntheses for complex oxygen ether linked carbohydrates.
The present invention provides saccharide compounds wherein the linkage is less susceptible to hydrolysis and methods for their preparation.
SUMMARY OF THE INVENTION
This invention provides a compound having the structure I,
wherein each R, independently, is selected from the group consisting of hydrogen, hydroxy, alkoxy having up to 8 carbon atoms, acyloxy having up to 8 carbon atoms, acylamino having up to 8 carbon atoms, C
1
to C
20
hydrocarbyl and substituted hydrocarbyl and amino;
R
3
is selected from the group consisting of H, C
1
to C
20
hydrocarbyl and substituted hydrocarbyl;
m is 0 or 1, and
n and n′ are, independently, 4 or 5.
Also provided are compounds containing three or more rings characterized in that the linkage between the several rings is a triazolyl group-containing moiety of the structure
where m and R
3
are defined as above.
This invention provides a compound of the structure II, wherein R
1
is selected from the group consisting of H, Na, C
1
-C
20
alkyl, wherein R
2
is selected from the group consisting of hydroxy, alkoxy having from 1 to 8 carbon atoms, acyloxy having from 1 to 8 carbon atoms, acylamino having
from 1 to 8 carbon atoms, amino, hydrogen, and guanidino;
wherein R
3
is selected from the group consisting of H, C
1
to C
20
hydrocarbyl, and substituted hydrocarbyl;
wherein R
4
is selected from the group consisting of H, acyl having from 1 to 8 carbon atoms, and alkyl having 1 to 20 carbon atoms;
wherein R
6
and R
6′
are selected from the group consisting of H, OH, C
1
to C
20
alkoxy, C
1
to C
20
substituted alkoxy, mono-, di- or oligosaccharide, and alkylideneoxy taken together with R
7′
when R
7′
is not H, provided that one of R
6
and R
6′
must be H but R
6
and R
6′
may not both be H; and
R
7
and R
7′
are selected from the group consisting of H, acyl having from 1 to 8 carbon atoms, C
1
to C
20
alkyl, aryl, and alkylidene taken together with an adjacent R
6
, R
6′
, R
7
or R
7′
.
Also provided are a compound of the structure III, wherein R
3
is selected from the group consisting of H, C
1
to C
20
hydrocarbyl, and C
1
to C
20
substituted hydrocarbyl; R
8
is selected from the group consisting of H, alkyl having from 1 to 20 carbon atoms, and acyl having from 1 to 8 carbon atoms;
wherein R
6
and R
6′
are selected from the group consisting of H, OH, C
1
to C
20
alkoxy, C
1
to C
20
substituted alkoxy, mono-, di- or oligosaccharide, and alkylideneoxy taken together with R
7′
, when R
7′
is not H, provided that one of R
6
and R
6′
must be H but R
6
and R
6′
may not both be H; and
wherein R
7
and R
7′
are selected from the group consisting of H, acyl having from 1 to 8 carbon atoms, C
1
to C
20
alkyl, aryl, and alkylidene taken together with an adjacent R
6
, R
6′
, R
7
or R
7′
.
Also disclosed is a process for the preparation of a compound having the structure I, comprising: contacting azides of the structure IA:
wherein R is selected from the group consisting of hydrogen, hydroxy, alkoxy having up to 8 carbon atoms, acyloxy having up to 8 carbon atoms, acylamino having up to 8 carbon atoms, C
1
to C
20
hydrocarbyl or substituted hydrocarbyl and amino; n and n′ are, independently, 4 or 5, and m is 0 or 1, with compounds of the structure IB
wherein R is as described above and R
3
is selected from the group consisting of H, C
1
to C
20
hydrocarbyl and substituted hydrocarbyl.
The present invention also discloses a process for the preparation of a combinatorial library of compounds of the structure I, comprising contacting one or more azides of the structure IA:
wherein R is selected from the group consisting of hydrogen, hydroxy, alkoxy having up to 8 carbon atoms, acyloxy having up to 8 carbon atoms, acylamino having up to 8 carbon atoms, C
1
to C
20
hydrocarbyl and substituted hydrocarbyl and amino; n and n′ are, independently, 4 or 5, and m is 0 or 1, with one or more compounds of the structure IB
wherein R is as described above and R
3
is selected from the group consisting of H, C
1
to C
20
hydrocarbyl and substituted hydrocarbyl.


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