Method for synthesizing 2-cyano-3,12-dioxoolean-1, 9(11)-dien-28-oic acid methyl ester and derivatives thereof

1. A method for preparing a triterpenoid compound comprising:

(a) methylating the carboxylic acid group of a compound of Formula I to afford a methyl ester;

(b) oxidizing the hydroxyl group of the methyl ester and forming a double bond in Ring A to form an enone;

(c) epoxidating Ring C of the enone to form an epoxide; and

(d) forming a C-ring enol and halogenating the A-ring enone to yield a compound of Formula II

wherein

X 1 is oxygen, dashed bonds a and a′ are present, X 2 is hydrogen and dashed bonds b and b′ are absent, or

X is oxygen, dashed bonds b and b′ are present, X 1 is hydrogen and dashed bonds a and a′ are absent;

Y is —CH 2 — or —CH 2 —CH 2 —;

R 1 , R 2 , R 3 and R 4 are each independently a hydrogen, hydroxyl, alkyl, substituted alkyl, alkenyl, alkoxy or substituted alkoxy group;

R 5 and R 6 are each independently hydrogen, halo, alkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl, acyl, alkoxy, aryloxy, aralkoxy, heteroaryloxy, hetero-aralkoxy, acyloxy, alkylamino, dialkyl-amino, arylamino, aralkylamino, hetero-arylamino, heteroaralkylamino, amido, or a substituted version of any of these groups, or

R 5 and R 6 are taken together and are alkanediyl, alkenediyl, arenediyl, alkoxydiyl, alkenyloxydiyl, alkylaminodiyl, alkenylaminodiyl, or alkenylaminooxydiyl; and

R 7 is hydrogen, hydroxy or oxo.

2. The method of claim 1 , wherein the compound of Formula I is oleanolic acid, ursolic acid, betulinic acid, sumaresinolic acid or hederagenin.

3. The method of claim 1 , wherein step (a) comprises an electrophilic methyl source.

4. The method of claim 1 , wherein step (b) comprises an iodine oxidizing agent.

5. The method of claim 1 , wherein step (c) comprises a peroxyacid.

6. The method of claim 1 , wherein step (d) comprises a hydrogen halide and diatomic halogen molecule.

7. The method of claim 1 , further comprising the step of contacting a compound of Formula II with a cyanide ion source.

8. The method of claim 1 , further comprising aminating the compound of Formula II.

9. The method of claim 8 , wherein amination comprises a Buchwald-Hartwig amination reaction.

10. The method of claim 1 , further comprising coupling or cross-coupling an alkyl, alkenyl, alkynyl or aryl group to a compound of Formula II.

11. The method of claim 10 , wherein said coupling or cross-coupling comprises a Sonogashira, Suzuki, Stille, or Negishi reaction.

12. A method for preparing 2-cyano-3,12-dioxoolean-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me), wherein said method comprises the following series of reactions