Methods for the purification of deoxycholic acid
Synthetic methods for preparing deoxycholic acid and intermediates thereof, high purity synthetic deoxycholic acid, compositions and methods of use are provided. Also, provided are processes for the synthesis of 12-keto or 12-α-hydroxysteroids from Δ-9,11-ene, 11-keto or 11-hydroxy-β-steroids. This invention is also directed to novel compounds prepared during the synthesis. This invention is also directed to the synthesis of deoxycholic acid starting from hydrocortisone.
1. A compound of formula 1:
wherein
Pg is a hydroxyl protecting group,
R is hydrogen, hydroxyl, or —OPg, R 1 is the 17-side chain of a bile acid selected from the group consisting of cholic acid, deoxycholic acid, taurocholic acid, and glycocholic acid, wherein the carboxyl functionality of said side chain is optionally esterified with a C 1 -C 6 alkyl group, and R 2 is hydrogen, or R 1 and R 2 together with the carbon atom attached thereto form a keto or a keto protecting group, and
each of R 3 , R 4 and R 5 is independently C 1 -C 3 alkyl.
2. The compound of claim 1 , wherein the compound of formula 1 is selected from the group consisting of compounds 42, 43, 44, 45 and 46:
3. A compound of formula 5
wherein
Pg is a hydroxyl protecting group;
R is hydrogen, hydroxyl, or —OPg, R 1 is the 17-side chain of a bile acid selected from the group consisting of cholic acid, deoxycholic acid, taurocholic acid, and glycocholic acid, wherein the carboxyl functionality of said side chain is optionally esterified with a C 1 -C 6 alkyl group, and R 2 is hydrogen, or R 1 and R 2 together with the carbon atom attached thereto form a keto or a keto protecting group; and each of R 3 , R 4 and R 5 is independently C 1 -C 3 alkyl.
4. The compound of claim 3 , wherein the compound of formula 5 is selected from the group consisting of compounds 48, 49, 50, 51 and 52:
5. The compound of claim 1 , wherein R 1 is selected from the group consisting of
wherein R 6 is lower alkyl and the wavy line represents the point of connection to the 17-position of steroidal scaffold.
6. The compound of claim 1 , wherein R 1 and R 2 together with the carbon atom attached thereto form a keto group.
7. The compound of claim 1 , wherein R 1 and R 2 together with the carbon atom attached thereto form:
wherein n is 1, 2, or 3 and the wavy line represents the point of connection to the rest of the molecule.
8. The compound of claim 1 , wherein R is hydrogen.
9. The compound of claim 3 , wherein R 1 is selected from the group consisting of
wherein R 6 is lower alkyl and the wavy line represents the point of connection to the 17-position of steroidal scaffold.
10. The compound of claim 3 , wherein R 1 and R 2 together with the carbon atom attached thereto form a keto group.
11. The compound of claim 3 , wherein R 1 and R 2 together with the carbon atom attached thereto form:
wherein n is 1, 2, or 3 and the wavy line represents the point of connection to the rest of the molecule.
12. The compound of claim 3 , wherein R is hydrogen.