Preparation of (S,S)-secoisolariciresinol diglucoside and (R,R)-secoisolariciresinol diglucoside

1. A process for preparing a compound of formula ((S,S)-SDG-1)

the process comprising:

(a) reacting a compound of formula (6)

with a compound of formula (7)

to prepare a compound of formula ((S,S)-S3)

(b) cleaving benzyl ethers of the compound of formula ((S,S)-S3), followed by a separation procedure to prepare a compound of formula ((S,S)-8)

 and

(c) deprotecting the compound of formula ((S,S)-8) to prepare the compound of formula ((S,S)-SDG-1).

2. The process of claim 1 , wherein said reacting is carried out in the presence of a Lewis acid.

3. The process of claim 2 , wherein said Lewis acid is TMSOTf.

4. The process of claim 3 , wherein said reacting is carried out in the presence of activated molecular sieves.

5. The process of claim 1 , wherein said cleaving is carried out in the presence of H 2 and Pd/C in MeOH.

6. The process of claim 1 , wherein said separation procedure is carried out using preparative thin layer chromatography.

7. The process of claim 1 , wherein said deprotecting is carried out in a solution of NaOMe and MeOH.

8. The process of claim 1 , wherein said compound of formula (6) is prepared by the process comprising reacting a compound of formula (S2)

with a reducing agent to prepare the compound of formula (6).

9. The process of claim 8 , wherein said reducing agent is lithium aluminum hydride (LAH) in THF.

10. The process of claim 8 , wherein said compound of formula (S2) is prepared by the process comprising reacting a compound of formula (S1)

with a benzylating agent to prepare the compound of formula (S2).

11. The process of claim 10 , wherein said benzylating agent is BnBr and NaH.

12. The process of claim 10 , wherein said compound of formula (S1) is prepared by the process comprising reacting a compound of formula (5)

with a reducing agent to prepare the compound of formula (S1).

13. The process of claim 12 , wherein said reducing agent is H 2 and Pd/C.

14. The process of claim 12 , wherein said compound of formula (5) is prepared by the process comprising reacting a compound of formula (4)

with vanillin by a Stobbe condensation reaction, followed by an esterification reaction to prepare the compound of formula (5).

15. The process of claim 14 , wherein said Stobbe condensation reaction is carried out in MeOH and in the presence of lithium.

16. The process of claim 15 , wherein said lithium is in the form of lithium wires.

17. The process of claim 14 , wherein said compound of formula (4) is prepared by the process comprising reacting vanillin with methyl succinate via a Stobbe condensation reaction, followed by an esterification reaction.

18. The process of claim 17 , wherein said Stobbe condensation reaction is carried out in MeOH and in the presence of lithium wires.

19. A process for preparing a compound of formula ((S,S)-SDG-1)

the process comprising:

(a) reacting a compound of formula (S2)

with a reducing agent to prepare a compound of formula (6)

(b) reacting the compound of formula (6) with a compound of formula (7)

to prepare a compound of formula ((S,S)-S3)

(c) cleaving benzyl ethers of the compound of formula ((S,S)-S3), followed by a separation procedure to prepare a compound of formula ((S,S)-8)

and

(d) deprotecting the compound of formula ((S,S)-8) to prepare the compound of formula ((S,S)-SDG-1).

20. A process for preparing a compound of formula ((S,S)-SDG-1)

the process comprising:

(a) reacting a compound of formula (5)

with a reducing agent to prepare a compound of formula (S1)

(b) reacting the compound of formula (S1)

with a benzylating agent to prepare a compound of formula (S2)

(c) reacting the compound of formula (S2) with a reducing agent to prepare a compound of formula (6)

(d) reacting the compound of formula (6) with a compound of formula (7)

to prepare a compound of formula ((S,S)-S3)

(e) cleaving benzyl ethers of the compound of formula ((S,S)-S3), followed by a separation procedure to prepare a compound of formula ((S,S)-8)

and

(f) deprotecting the compound of formula ((S,S)-8) to prepare the compound of formula ((S,S)-SDG-1).

21. A process for preparing a compound of formula ((R,R)-SDG-2)

the process comprising:

(a) reacting a compound of formula (6)

with a compound of formula (7)

to prepare a compound of formula ((R,R)-S4)

(b) cleaving benzyl ethers of the compound of formula ((R,R)-S4), followed by a separation procedure to prepare a compound of formula ((R,R)-9)

and

(c) deprotecting the compound of formula ((R,R)-9) to prepare the compound of formula ((R,R)-SDG-2).

22. The process of claim 21 , wherein said reacting is carried out in the presence of TMSOTf.

23. The process of claim 21 , wherein said reacting is carried out in the presence of activated molecular sieves.

24. The process of claim 21 , wherein said cleaving is carried out in the presence of H 2 and Pd/C in MeOH.

25. The process of claim 21 , wherein said separation procedure is carried out using preparative thin layer chromatography.

26. The process of claim 21 , wherein said deprotecting is carried out in a solution of NaOMe and MeOH.

27. The process of claim 21 , wherein said compound of formula (6) is prepared by the process comprising reacting a compound of formula (S2)

with a reducing agent to prepare the compound of formula (6).

28. The process of claim 27 , wherein said reducing agent is lithium aluminum hydride (LAH) in THF.

29. The process of claim 27 , wherein said compound of formula (S2) is prepared by the process comprising reacting a compound of formula (S1)

with a benzylating agent to prepare the compound of formula (S2).

30. The process of claim 29 , wherein said benzylating agent is BnBr and NaH.

31. The process of claim 29 , wherein said compound of formula (S1) is prepared by the process comprising reacting a compound of formula (5)

with a reducing agent to prepare the compound of formula (S1).

32. The process of claim 31 , wherein said reducing agent is H 2 and Pd/C.

33. The process of claim 31 , wherein said compound of formula (5) is prepared by the process comprising reacting a compound of formula (4)

with vanillin by a Stobbe condensation reaction, followed by an esterification reaction to prepare the compound of formula (5).

34. The process of claim 33 , wherein said Stobbe condensation reaction is carried out in MeOH and in the presence of lithium.

35. The process of claim 33 , wherein said lithium is in the form of lithium wires.

36. The process of claim 33 , wherein said compound of formula (4) is prepared by the process comprising reacting vanillin with methyl succinate via a Stobbe condensation reaction, followed by an esterification reaction.

37. The process of claim 36 , wherein said Stobbe condensation reaction is carried out in MeOH and in the presence of lithium wires.

38. A process for preparing a compound of formula ((R,R)-SDG-2)

the process comprising:

(a) reacting a compound of formula (S2)

with a reducing agent to prepare a compound of formula (6)

(b) reacting the compound of formula (6) with a compound of formula (7)

to prepare a compound of formula ((R,R)-S4)

(c) cleaving benzyl ethers of the compound of formula ((R,R)-S4), followed by a separation procedure to prepare a compound of formula ((R,R)-9)

and

(d) deprotecting the compound of formula ((R,R)-9) to prepare the compound of formula ((R,R)-SDG-2).

39. A process for preparing a compound of formula ((R,R)-SDG-2)

the process comprising:

(a) reacting a compound of formula (5)

with a reducing agent to prepare a compound of formula (S1)

(b) reacting the compound of formula (S1)

with a benzylating agent to prepare a compound of formula (S2)

(c) reacting the compound of formula (S2) with a reducing agent to prepare a compound of formula (6)

(d) reacting the compound of formula (6) with a compound of formula (7)

to prepare a compound of formula ((R,R)-S4)

(e) cleaving benzyl ethers of the compound of formula ((R,R)-S3), followed by a separation procedure to prepare a compound of formula ((R,R)-9)

and

(f) deprotecting the compound of formula ((R,R)-9) to prepare the compound of formula ((R,R)-SDG-2).