Trioxacarcins and uses thereof

1. A compound of the Formula (I):

or a pharmaceutically acceptable form thereof;

wherein:

R 1 is hydrogen or ═O;

each instance of R 2 and R 3 is hydrogen;

R 4 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR D1 ; —C(═O)R D2 ; —CO 2 R D2 ; —CN; —SCN; —SR D1 ; —SOR D1 ; —SO 2 R D2 ; —NO 2 ; —N 3 ; —N(R D2 ) 2 ; —NR D2 C(═O)R D2 ; —NR D2 C(═O)N(R D2 ) 2 ; —OC(═O)OR D1 ; —OC(═O)R D2 ; —OC(═O)N(R D2 ) 2 ; —NR D2 C(═O)OR D1 ; or —C(R D2 ) 3 ; wherein each occurrence of R D1 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; and wherein each occurrence of R D2 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; substituted hydroxyl; substituted thiol; amino; or substituted amino; or two R D2 groups are optionally joined to form a heterocyclyl or heteroaryl ring;

R 5 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR E1 ; —C(═O)R E2 ; —CO 2 R E1 ; —CN; —SCN; —SR E1 ; —SOR E1 ; —SO 2 R E2 ; —NO 2 ; —N 3 ; —N(R E2 ) 2 ; —NR E2 C(═O)R E2 ; —NR E2 C(═O)N(R E2 ) 2 ; —OC(═O)OR E1 ; —OC(═O)R E2 ; —OC(═O)N(R E2 ) 2 ; —NR E2 C(═O)OR E1 ; or —C(R E2 ) 3 ; wherein each occurrence of R E1 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; and wherein each occurrence of R E2 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; substituted hydroxyl; substituted thiol); amino; or substituted amino; or two R E2 groups are optionally joined to form a heterocyclyl or heteroaryl ring;

R 6 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F1 ; —C(═O)R F2 ; —CO 2 R F1 ; —CN; —SCN; —SR F1 ; —SOR F1 ; —SO 2 R F2 ; —NO 2 ; —N 3 ; —N(R F2 ) 2 ; —NR F2 C(═O)R F2 ; —NR F2 C(═O)N(R F2 ) 2 ; —OC(═O)OR F1 ; —OC(═O)R F2 ; —OC(═O)N(R F2 ) 2 ; —NR F2 C(═O)OR F1 ; or —C(R F2 ) 3 ; wherein each occurrence of R F1 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; and wherein each occurrence of R F2 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; substituted hydroxyl; substituted thiol; amino; or substituted amino; or two R F2 groups are optionally joined to form a heterocyclyl or heteroaryl ring;

R 7 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G1 ; —C(═O)R G2 ; —-CO 2 R G1 ; —CN; —SCN; —SR G1 ; —SOR G1 ; —SO 2 R G2 ; —NO 2 ; —N 3 ; —N(R G ) 2 ; —NR G2 C(═O)R G2 ; —NR G2 C(═O)N(R G2 ) 2 ; —OC(═O)OR G1 ; —OC(═O)R G2 ; —OC(═O)N(R G2 ) 2 ; —NR G2 C(═O)OR G1 ; or —C(R G2 ) 3 ; wherein in each occurrence of R G1 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; and wherein each occurrence of R G2 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; substituted hydroxyl; substituted thiol; amino; or substituted amino; or two R G2 groups are optionally joined to form a heterocyclyl or heteroaryl ring;

R 8 is —OR H1 , wherein each occurrence of R H1 is independently hydrogen, carbohydrate, an oxygen-protecting group, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; or acyl;

R 9 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR I1 ; —C(═O)R I2 ; —CO 2 R I1 ; —CN; —SCN; —SR I1 ; —SOR I1 ; —SO 2 R I2 ; —NO 2 ; —N 3 ; —N(R I2 ) 2 ; —NR I2 C(═O)R I2 ; —NR I2 C(═O)N(R I2 ) 2 ; —OC(═O)OR I1 ; —OC(═O)R I2 ; —OC(═O)N(R I2 ) 2 ; —NR I2 C(═O)OR I1 ; or —C(R I2 ) 3 ; wherein each occurrence of R I1 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; each occurrence of R I2 is independently hydrogen; carbohydrate; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; substituted hydroxyl; substituted thiol; amino; or substituted amino); or two R I2 groups are optionally joined to form a heterocyclyl or heteroaryl ring;

or R 4 and R 7 are optionally be taken together with the intervening carbon atoms to form an optionally substituted cyclic moiety;

or R 6 and R 7 are optionally be taken together with the intervening carbon atoms to form an optionally substituted cyclic moiety.

2. The compound of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable form thereof.

3. The compound of claim 2 , wherein the compound is of formula:

or a pharmaceutically acceptable form thereof.

4. The compound of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable form thereof.

5. The compound of claim 1 , wherein R 1 is hydrogen.

6. The compound of claim 1 , wherein R 4 is —OR D1 .

7. The compound of claim 1 , wherein R 5 is —OR E1 .

8. The compound of claim 1 , wherein R 6 is C 1-6 alkyl.

9. The compound of claim 1 , wherein R 7 is hydrogen.

10. The compound of claim 1 , wherein R 8 is —OR H1 .

11. The compound of claim 10 , wherein R H1 is hydrogen, a carbohydrate, or C 1-6 alkyl.

12. The compound of claim 11 , wherein the carbohydrate is:

wherein R a and R b are independently selected from the group consisting of hydrogen; carbohydrate; an oxygen protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; acyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl.

13. The compound of claim 1 , wherein R 9 is —CH(OR I3 ) 2 ; and each occurrence of R I3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a carbohydrate.

14. The compound of claim 1 , wherein R 1 is ═O.

15. The compound of claim 6 , wherein R D1 is C 1-6 alkyl.

16. The compound of claim 7 , wherein R E1 is hydrogen.

17. The compound of claim 13 , wherein R 9 is —CH(OCH 3 ) 2 .

18. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable form thereof.

19. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient.

20. A method of treating a disease, disorder or condition selected from the group consisting of proliferative diseases, diabetic retinopathy, inflammatory diseases, autoimmune diseases, and infectious diseases, comprising administering to a subject an effective amount of a compound of claim 1 or pharmaceutically acceptable form thereof.