Preparation of (s,s)-secoisolariciresinol diglucoside and (r,r)-secoisolariciresinol diglucoside

Patent metadata

Field	Value
Publication number	US-2016137682-A1
Application number	US-201414897181-A
Country	US
Kind code	A1
Filing date	Jun 10, 2014
Priority date	Jun 10, 2013
Publication date	May 19, 2016
Grant date	—

Abstract

The invention relates to processes for preparing (S,S)-secoisolariciresinol diglucoside and (R,R)-secoisolariciresinol diglucoside and compositions comprising the same.

First claim

What is claimed is:

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 esterification reaction is carried out with MeOH in the presence of H 2 SO 4 .

18 . 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.

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

20 . The process of claim 18 , wherein said esterification reaction is carried out with MeOH in the presence of H 2 SO 4 .

21 . 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).

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

23 . The process of claim 22 , wherein said reacting of step (a) 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 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 reducing agent is lithium aluminum hydride (LAH) in THF.

28 . The process of claim 21 , wherein said compound of formula (S2) is prepared by the process comprising reacting a compound of formula (S1)

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

29 . The process of claim 28 , wherein said benzylating agent is BnBr and NaH.

30 . The process of claim 28 , 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).

31 . The process of claim 30 , wherein said reducing agent is H 2 and Pd/C.

32 . The process of claim 30 , 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).

33 . The process of claim 32 , wherein said Stobbe condensation reaction is carried out in MeOH and in the presence of

Assignees

• Univ Pennsylvania
• Scripps Research Inst

Inventors

• Christofidou-Solomidou Melpo
• Nicolaou Kyriacos C
• Valiulin Roman A
• Simmons Nicholas
• Heretsch Philipp M

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P17/18

  Antioxidants, e.g. antiradicals (preparations for protection against sunlight A61Q17/00) · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07H15/203

  Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems · CPC title

• C07C41/18

  by reactions not forming ether-oxygen bonds · CPC title