Methods of preparing nicotinamide riboside and derivatives thereof

Patent metadata

Field	Value
Publication number	US-10815262-B2
Application number	US-201815905922-A
Country	US
Kind code	B2
Filing date	Feb 27, 2018
Priority date	Jul 29, 2013
Publication date	Oct 27, 2020
Grant date	Oct 27, 2020

Abstract

The invention relates to methods of preparing nicotinamide riboside and derivatives thereof. In an aspect, the invention relates to a method of preparing a compound of formula (I), wherein n is 0 or 1; m is 0 or 1; Y is O or S; R1 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted primary or secondary amino, and substituted or unsubstituted azido; R2-R5, which may be the same or different, are each independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, and substituted or unsubstituted aryl; and X− is an anion, selected from an anion of a substituted or unsubstituted carboxylic acid, a halide, a substituted or unsubstituted sulfonate, a substituted or unsubstituted phosphate, a substituted or unsubstituted sulfate, a substituted or unsubstituted carbonate, and a substituted or unsubstituted carbamate.

First claim

The invention claimed is:

1. A compound of formula (III)

wherein:
n is 0 or 1;
m is 0 or 1;
Y is O or S;
R 1 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted primary or secondary amino, and substituted or unsubstituted azido;
R 2 -R 5 , which may be the same or different, are each independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, and substituted or unsubstituted aryl; and
R 6 , R 7 and R 8 , which may be the same or different, are each independently a hydroxyl protecting group or are each H, provided that when n is 1, m is 1, Y is O, R 1 is methyl, and R 2 -R 5 are each H, then R 6 , R 7 , and R 8 are not all simultaneously H or unsubstituted acetyl; further provided that when n is 1, m is 1, Y is O, R 1 is methyl, R 3 and R 4 are methyl, and R 2 and R 5 are each H, then R 6 , R 7 and R 8 are not all simultaneously H or unsubstituted acetyl; and yet further provided that when n is 0, m is 1, R 1 is NH 2 , and R 2 -R 5 are each H, then R 6 , R 7 , and R 8 are not all simultaneously H or unsubstituted benzoyl.

2. A compound of claim 1 , wherein R 6 , R 7 and R 8 are each H.

3. A compound according to claim 1 , wherein R 6 , R 7 and R 8 are each independently an ester-type protecting group, an ether-type protecting group, or a silyl-type protecting group.

4. A compound according to claim 3 , wherein the R 6 , R 7 and R 8 moieties are selected from substituted and unsubstituted acetyl, and substituted and unsubstituted benzoyl.

5. A compound according to claim 3 , wherein the ester-type protecting group is a protecting group selected from acetyl, propionyl, isopropionyl, benzoyl, and trihaloacetyl.

6. A compound according to claim 5 , wherein the R 6 , R 7 and R 8 moieties are selected from substituted and unsubstituted acetyl, and substituted and unsubstituted benzoyl.

7. A compound according to claim 3 , wherein the ester-type protecting group is a protecting group selected from trifluoroacetyl or trichloroacetyl, and provided that when n is 0 and m is 1, R 1 is not NH 2 .

8. A compound according to claim 3 , wherein the ether-type protecting group is a protecting group selected from benzyl, p-methoxybenzyl, methoxymethyl and allyl ethers.

9. A compound according to claim 3 , wherein the silyl-type protecting group is a protecting group selected from trimethylsilyl, triethylsilyl, triisopropylsilyl, 2-(trimethylsilyl)ethoxymethyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl and tetraisopropyldisilyl.

10. A compound of claim 1 , wherein at least two of R 6 , R 7 and R 8 are selected from unsubstituted acetyl or unsubstituted benzoyl.

11. A compound according to claim 1 , which is triacetyl O-ethyl-1,4-dihydronicotinate riboside:

12. A compound of formula (IV)

wherein
n is 1;
m is 1;
Y is O;
R 1 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted primary or secondary amino, and substituted or unsubstituted azido;
R 2 -R 5 are each H; and
R 6 , R 7 and R 8 , which may be the same or different, are each independently a hydroxyl protecting group; and
X − is an anion selected from an anion of a substituted or unsubstituted carboxylic acid, a halide, a substituted or unsubstituted sulfonate, a substituted or unsubstituted phosphate, a substituted or unsubstituted sulfate, a substituted or unsubstituted carbonate, and a substituted or unsubstituted carbamate;

provided that when n is 1, m is 1, Y is O, R 1 is H or NH 2 , R 2 -R 5 are each H, and X − is a substituted sulfonate, then R 6 , R 7 , and R 8 are not all simultaneously H or unsubstituted acetyl or unsubstituted benzoyl.

13. A compound of formula:

wherein X − is an anion selected from an anion of a substituted or unsubstituted carboxylic acid, a halide, a substituted or unsubstituted sulfonate, a substituted or unsubstituted phosphate, a substituted or unsubstituted sulfate, a substituted or unsubstituted carbonate, and a substituted or unsubstituted carbamate, provided that X − is not trifluoromethylsulfonate.

14. A compound of claim 1 , wherein:
Y n R 1 is NH 2 or —OCH 2 CH 3 ; and
R 2 -R 5 are all hydrogens.

15. The compound of claim 14 , wherein R 6 , R 7 and R 8 , are each the same group.

16. A compound of claim 10 , wherein at least two of R 6 , R 7 and R 8 are selected from unsubstituted acetyl or unsubstituted benzoyl and provided that when n is 0 and m is 1, R 1 is not NH 2 .

17. The compound of claim 12 , wherein X − is an anion selected from an anion of a substituted or unsubstituted carboxylic acid, a substituted or unsubstituted phosphate, a substituted or unsubstituted sulfate, a substituted or unsubstituted carbonate, and a substituted or unsubstituted carbamate.

18. The compound of claim 12 , wherein X − is an anion selected from acetate, formate, trifluoroacetate, glutamate, lactate, and aspartate.

19. The compound of claim 13 , wherein X − is an anion selected from an anion of a substituted or unsubstituted carboxylic acid, a halide, a substituted or unsubstituted phosphate, a substituted or unsubstituted sulfate, a substituted or unsubstituted carbonate, and a substituted or unsubstituted carbamate.

20. The compound of claim 13 , wherein X − is an anion selected from acetate, formate, trifluoroacetate, glutamate, lactate and aspartate.

Assignees

• Univ Belfast

Inventors

• Migaud Marie
• Redpath Philip
• Crossey Kerri
• Doherty Mark

Classifications

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• A23L33/10

  using additives (addition of substantially indigestible substances A23L33/21) · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H19/048 Primary

  Pyridine radicals · CPC title

• C07H1/06

  Separation; Purification · CPC title