Method for the production of D-chiroinositol

• US 5,516,950 A
• Filed: 02/14/1995
• Issued: 05/14/1996
• Est. Priority Date: 04/15/1994
• Status: Expired due to Fees

• Current Assignee: INSMED Pharmaceuticals, Inc. (Insmed Incorporated)
• Original Assignee: INSMED Pharmaceuticals, Inc. (Insmed Incorporated)
• Inventors: Samanaryke, Gamini, Piccariello, Thomas
• Primary Examiner(s): LONE, WERREN
• Application Number:
  US08/389,709
• Time in Patent Office: 455 Days
• Field of Search: 568/822, 568/832, 568/833
• US Class Current: 568/833
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 29/103 of cyclic ethers
• CPC Class Codes: C07C 29/143 of ketones
• CPC Class Codes: C07C 35/16 Inositols
• CPC Class Codes: C07C 45/00 Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
• CPC Class Codes: C07C 49/497 a keto group being part of a six-membered ring
• CPC Class Codes: C12C 11/02 Pitching yeast
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention relates to the synthesis of D-chiroinositol from a dialdose, comprising the steps of condensing the dialdose by an acyloin condensation reaction to form an inosose, protecting the carbon atoms at the 2, 3, 4 and 5 positions, reducing the ketone of the inosose and removing the protecting groups. In addition, a method of preparing mannodialdose from mannuronic acid is disclosed.

Claims

1. A method for the synthesis of mannodialdose from mannuronic acid comprising the steps of:

a. reacting mannuronic acid with a trisubstituted-boroxin to form a boronate ester; and

b. reducing the boronate ester with dialkylboron to form mannodialdose.

2. The method of claim 1 wherein the substituent on the boroxin is selected from the group consisting of alkyl and aryl groups.

3. The method of claim 1 wherein the substituent on the boroxin is selected from the group consisting of ethyl and methyl.

4. A method for the synthesis of an inosose from a dialdose, comprising condensing the dialdose by an acyloin condensation reaction catalyzed by a thiazolium salt.

5. The method of claim 4 wherein the thiazolium salt is substituted at the 3-position with an alkyl or aryl group.

6. The method of claim 5 wherein the thiazolium salt is substituted at the 3-position with a benzyl group.

7. The method of claim 4 wherein the thiazolium salt is substituted at the 5-position with an alkyl, aryl or halo group.

8. The method of claim 7 wherein the thiazolium salt is substituted at the 5-position with a hydroxyethyl group.

9. The method of claim 4 wherein the dialdose is mannodialdose and the inosose is D-chiroinosose.

10. A method for the synthesis of an inositol from an inosose, comprising the steps of:

a. protecting the carbon atoms at the 2, 3, 4 and 5 positions of the inosose by forming a first five-membered ring which incorporates carbons 2 and 3, and a second five-membered ring which incorporates carbons 4 and 5;

b. reducing the ketone of the inosose to form a diol; and

c. removing the protecting groups by subjecting the diol to acid catalyzed hydrolysis.

11. The method of claim 10 wherein the ketone of the inosose is reduced under equilibrating conditions by refluxing the inosose in the presence of Raney nickel.

12. The method of claim 10 wherein the first and second five-membered rings comprise a carbon ketal and the ketone of the inosose is reduced under kinetic conditions by subjecting it to a hydride transfer reagent.

13. The method of claim 10 wherein the first and second five-membered rings comprise a boron ketal and the ketone of the inosose is reduced under kinetic conditions by subjecting it to a hydride transfer reagent.

14. The method of claim 10 wherein the inosose is D-chiroinosose and the inositol is D-chiroinositol.