Monosaccharide compounds and methods therefor

1. A monosaccharide compound of Formula I:

in which the monosaccharide ring is of the glucosamine or galactosamine configuration;

R 3 is a carboxylic acid mimetic selected from the group consisting of:

in which A and B are independently hydrogen, alkyl, trihaloalkyl or halo;

A 11 is hydroxy, optionally substituted carboxy or oxyaryl;

U is H, aryl, heteroaryl, alkyl, alkenyl or alkynyl each of which are optionally substituted with one or more of OH, SH, CF 3 , alkyl, alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine or guanidinium; and

R is O—Y, or

in which Y is,

in which Z 1 is selected from halo, optionally substituted S-aryl, optionally substituted S-heteroaryl, optionally substituted aryl or optionally substituted heteroaryl;

X is selected from O, NH or S;

Y 1 is selected from: (a) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkyl, optionally substituted arylalkyl, or (b) any one of:

in which Z 111 is selected from O, NH or S;

R 6 is selected from H, CONH 2 or COOH;

n is an integer of 0 to 4;

R 7 is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl;

R 8 is selected from H, OH, NH 2 , alkyl, alkenyl or alkynyl;

R 9 is selected from H, OH, NH 2 , or NHCO—R 10 in which R 10 is an optionally substituted alkyl;

R 11 is selected from an optionally substituted alkylene, optionally substituted cycloalkyl, optionally substituted heterocyclyl or optionally substituted heteroaryl; and

R 1 is selected from an optionally substituted acetyl, an optionally substituted C 3-8 acyl, an optionally substituted benzoyl, an optionally substituted napthoyl, an optionally substituted biphenylcarbonyl, a heteroaryl acyl, an optionally substituted bicycloacyl, an optionally substituted bicycloheteroacyl, wherein the substituent or optional substituent is selected from at least one of OH, SH, CF 3 , alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine or guanidinium.

2. The compound of claim 1 , wherein the optional substituents A 11 , Z 1 , R 7 , R 10 , R 11 , and R 1 are selected from at least one of OH, SH, CF 3 , alkyl, alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine and guanidinium.

3. The compound of claim 1 , having the Formula Ia:

wherein the monosaccharide ring is of the glucosamine or galactosamine configuration and the anomeric center is either the α or β configuration;

R 3 is as defined in claim 1 ; and

R 1 is:

(i) a benzoyl group which is optionally substituted with one or more OH, SH, CF 3 , alkyl, alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine or guanidinium;

(ii) a biphenylcarbonyl group which is optionally substituted on either one or both of the aromatic rings with one or more of OH, SH, CF 3 , alkyl, alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine or guanidinium; or

(iii) a heteroaryl acyl, sulfonamide, urea or carbamate; and

Y is as defined in claim 1 , in which the optional substituents for Z 11 are at least one of OH, SH, CF 3 , alkyl, alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, aryloxy, SO 2 NH 2 , amidine or guanidinium.

4. The compound of claim 1 , having the Formula Ib:

wherein the monosaccharide ring substitution is of the glucosamine or galactosamine configuration and the anomeric center is either the α or β configuration;

R 3 is defined as in claim 1 ;

R 1 is defined as in claim 3 ;

R 1 1 is

in which

X is O, NH or S; and

Y 1 is as defined in claim 1 in which R 7 is optionally substituted with at least one of OH, SH, CF 3 , alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine or guanidinium.

5. The compound of claim 1 , wherein said compound has antibacterial properties.

6. A composition comprising the compound of claim 1 .

7. A library comprising a plurality of different compounds of Formula I according to claim 1 .

8. A method for the preparation of a compound of Formula I according to claim 1 , which comprises glycosylating an intermediate compound of Formula IV with an alcohol or phenol acceptor,

in which L is a leaving group and L 1 is a protecting group.

9. A method for the preparation of a compound of Formula Ib according to claim 4 , which comprises acylating an intermediate compound of Formula V:

in which L 11 is hydrogen, NO 2 , halo, azido or alkoxy.

10. A method of screening for an antibiotic compound, which comprises:

(a) forming a library that comprises a plurality of different compounds of Formula I according to claim 1 ; and

(b) testing said library for antibiotic activity.

11. The method of claim 10 , further comprising:

(c) identifying in said library a compound having antibacterial activity.

12. An antibiotic compound identified by a method of screening for an antibiotic compound comprising:

(a) forming a library that comprises a plurality of different compounds of Formula I:

in which the monosaccharide ring is of the glucosamine or galactosamine configuration;

R 3 is a carboxylic acid mimetic selected from the group consisting of:

in which A and B are independently hydrogen, alkyl, trihaloalkyl or halo;

A 11 is hydroxy, optionally substituted carboxy or oxyaryl;

U is H, aryl, heteroaryl, alkyl, alkenyl or alkynyl each of which are optionally substituted with one or more of OH, SH, CF 3 , alkyl, alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine or guanidinium; and

R is O—Y, or

in which Y is,

in which Z 1 is selected from halo, optionally substituted S-aryl, optionally substituted S-heteroaryl, optionally substituted aryl or optionally substituted heteroaryl;

X is selected from O, NH or S;

Y 1 is selected from: (a) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkyl, optionally substituted arylalkyl, or (b) any one of:

in which Z 111 is selected from O, NH or S;

R 6 is selected from H, CONH 2 or COOH;

n is an integer of 0 to 4;

R 7 is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl;

R 8 is selected from H, OH, NH 2 , alkyl, alkenyl or alkynyl;

R 9 is selected from H, OH, NH 2 , or NHCO—R 10 in which R 10 is an optionally substituted alkyl;

R 11 is selected from an optionally substituted alkylene, optionally substituted cycloalkyl, optionally substituted heterocyclyl or optionally substituted heteroaryl; and

R 1 is selected from an optionally substituted acetyl, an optionally substituted C 3-8 acyl, an optionally substituted benzoyl, an optionally substituted napthoyl, an optionally substituted biphenylcarbonyl, a heteroaryl acyl, an optionally substituted bicycloacyl, an optionally substituted bicycloheteroacyl, wherein the substituent or optional substituent is selected from at least one of OH, SH, CF 3 , alkenyl, alkynyl, NO 2 , halo, SO 3 H, NH 2 , CO 2 H, azido, nitroso, alkoxy, SO 2 NH 2 , amidine or guanidinium; and

(b) testing said library for antibiotic activity.

13. A composition comprising the antibiotic compound of claim 12 .