Triterpene saponin variants, methods of synthesis and use thereof

1 . A compound of formula (I) or a pharmaceutically acceptable salt thereof,

wherein G is hydrogen, a branched trisaccharide of formula V or a stereoisomer of formula V

wherein W is CHO

wherein each occurrence of R P is independently hydrogen or OR x ;

wherein each occurrence of R x is independently hydrogen or an optionally substituted group selected from 6-10-membered aryl, benzyl, C 1-6 aliphatic, or C 1-6 heteroaliphatic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; or two R x are taken together to form a 5-7-membered heterocyclic ring having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;

wherein each occurrence of R x′ is independently an optionally substituted group selected from 6-10-membered aryl, benzyl, C 1-6 aliphatic, or C 1-6 heteroaliphatic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; or two R x′ are taken together to form a 5-7-membered heterocyclic ring having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;

wherein each occurrence of R y is OH or OR x ;

wherein is a single or double bond;

wherein V is hydrogen or OR x ;

wherein the —X—Z moiety is selected from the group consisting of

wherein Z comprises a carbohydrate domain having the structure:

wherein each occurrence of R 1 is R x or a carbohydrate domain having the structure:

wherein each occurrence of a, b, and c is independently 0, 1, or 2;

wherein d is an integer from 1-5, wherein each d bracketed structure may be the same or different; with the proviso that the d bracketed structure represents a furanose or pyranose moiety, and the sum of b and c is 1 or 2;

wherein R 0 is hydrogen or an optionally substituted moiety selected from the group consisting of acyl, C 1-10 aliphatic, C 1-6 heteroaliphatic, 6-10-membered aryl, arylalkyl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;

wherein each occurrence of R a , R b , R c , and R d is independently hydrogen, halogen, OH, OR, OR x , NR 2 , NHCOR, or an optionally substituted group selected from acyl, C 1-10 aliphatic, C 1-6 heteroaliphatic, 6-10-membered aryl, arylalkyl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each occurrence of R is independently hydrogen, an optionally substituted group selected from acyl, arylalkyl, 6-10-membered aryl, C1-12 aliphatic, or C1-12 heteroaliphatic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; or two R on the same nitrogen atom are taken with the nitrogen to form a 4-7-membered heterocyclic ring having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;

wherein R 2 is NHC(O)R 4 , OC(O)R 4 , OC(O)OR 4 , OC(O)NHR 4 , OC(O)SR 4 , NHC(O)OR 4 , NHC(O)NHR 4 , NHC(O)N(R 4 ) 2 , NHR 4 or N(R 4 ) 2 ;

wherein R 3 is hydrogen, halogen, CH 2 OR 1 , or an optionally substituted group selected from the group consisting of acyl, C 1-10 aliphatic, C 1-6 heteroaliphatic, 6-10-membered aryl, arylalkyl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, and 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;

wherein R 4 is T-R z , wherein T is a covalent bond or a bivalent C 1-12 saturated or unsaturated, straight or branched, aliphatic or heteroaliphatic chain, and

wherein R z is hydrogen, halogen, C(O)OR q , NC(O)OR q , OR q , NHC(O)R q , OR q , SR q , NHC(S)R q , OC(O)R q , OC(O)OR q , OC(O)NHR q , OC(O)SR q , NHC(O)OR q , NHC(O)NHR q , NHC(O)N(R q ) 2 , NHR q or N(R q ) 2 , or an optionally substituted group selected from acyl, arylalkyl, heteroarylalkyl, C 1-6 aliphatic, 6-10-membered aryl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur; or two R q on the same nitrogen atom are taken with the nitrogen to form a 4-7-membered heterocyclic ring having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, and

wherein R q is hydrogen, a detectable label, a protecting group, an optionally substituted group selected from acyl, arylalkyl, 6-10-membered aryl, C 1-12 aliphatic, and C 1-12 heteroaliphatic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, or

an optionally substituted group selected from acyl, arylalkyl, 6-10-membered aryl, C 1-12 aliphatic, and C 1-12 heteroaliphatic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, wherein the optionally substituted group further comprises a detectable label.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the —X—Z moiety is selected from the group consisting of

wherein a or β refer to the stereochemical configuration at the anomeric carbon in formula IX that is directly attached to the X moiety in formula I.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the —X—Z moiety is selected from the group consisting of

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the —X—Z moiety is

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein G is hydrogen.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein G is

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is (VII)

8 . The compound of claim 1 , wherein the compound is selected from the group consisting of

9 . The compound of claim 1 , wherein G is (VI)

and wherein Z is selected from the group consisting of formula C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, and mixtures thereof:

10 . The compound of claim 1 , wherein G is hydrogen or (VI)

wherein Z is

wherein R j is hydrogen,

wherein X′″ is I, 123 I, 124 I, 125 I 131 I, F, 18 F, or SnMe 3 .

11 . The compound of claim 1 , wherein G is hydrogen, wherein Z is

and wherein.

12 . A pharmaceutical composition, comprising:

compound of claim 1 or a pharmaceutically acceptable salt thereof,

an immunologically effective amount of an antigen; and

a pharmaceutically acceptable excipient.

13 . A method for immunizing a subject, comprising:

administering to the subject an effective amount of the pharmaceutical composition of claim 12 .

14 . A method for treating a disorder in a subject, comprising:

administering to the subject an effective amount of the pharmaceutical composition of claim 13 ,

wherein the disorder is cancer, an infectious disease or a neurodegenerative disorder.