Methods of preparing reduced nicotinamide riboside and derivatives thereof

Patent metadata

Field	Value
Publication number	US-2026062436-A1
Application number	US-202519382895-A
Country	US
Kind code	A1
Filing date	Nov 7, 2025
Priority date	Jul 29, 2013
Publication date	Mar 5, 2026
Grant date	—

Abstract

Methods of preparing nicotinamide riboside and derivatives thereof, are described. In an aspect, the invention relates to a method of making a compound of formula (II), or a salt, or solvate thereof:

wherein n is 0 or 1;
Y is O or S;
m is 1;
R 1 is selected from the group consisting of hydrogen, 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; and
R 2 -R 5 are each H.

First claim

We claim:

1 . A nicotinamide riboside salt compound having the formula:

wherein X − is an anion selected from the group consisting of an anion of a substituted monocarboxylic acid, an anion of an unsubstituted monocarboxylic acid other than an anion of formic acid, an anion of a substituted or unsubstituted dicarboxylic acid, an anion of a substituted or unsubstituted phosphate, an anion of a substituted or unsubstituted sulfate, an anion of a substituted or unsubstituted carbonate, and an anion of a substituted or unsubstituted carbamate.

2 . The compound of claim 1 , wherein X − is an anion of a substituted or unsubstituted dicarboxylic acid.

3 . The compound of claim 1 , wherein the compound has greater than 90% chemical purity, and comprises at least 98% diastereomeric purity of the beta-D-ribofuranosyl configuration.

4 . The compound of claim 1 , wherein the compound contains <3000 ppm methanol, less than or equal to 0.1% (w/w) other solvents, and less than or equal to 0.2% (w/w) water.

5 . A triacetyl nicotinamide riboside salt compound having the formula:

wherein X − is an anion selected from the group consisting of an anion of a substituted monocarboxylic acid, an anion of an unsubstituted monocarboxylic acid other than an anion of formic acid, an anion of a substituted or unsubstituted dicarboxylic acid, an anion of a substituted or unsubstituted phosphate, an anion of a substituted or unsubstituted sulfate, an anion of a substituted or unsubstituted carbonate, and an anion of a substituted or unsubstituted carbamate.

6 . The compound of claim 5 , wherein X − is an anion of a substituted or unsubstituted dicarboxylic acid.

7 . The compound of claim 5 , wherein the compound has greater than 90% chemical purity, and comprises at least 98% diastereomeric purity of the beta-D-ribofuranosyl configuration.

8 . The compound of claim 5 , wherein the compound contains <3000 ppm methanol, less than or equal to 0.1% (w/w) other solvents, and less than or equal to 0.2% (w/w) water.

9 . A method of making a compound of formula (IVA), or a salt, or a solvate thereof:

the method comprising the steps of:
(a) providing a compound of formula (IIIA)

wherein n is 0 or 1;
Y is O or S;
m is 1;
R 1 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted primary or secondary amino, and azido;
R 2 -R 5 are each H; and
R 6 , R 7 and R 8 are each independently selected from the group consisting of hydrogen, an ester-type protecting group, an ether-type protecting group, and a silyl protecting group;
(b) oxidizing the compound of formula (IIIA) to provide a compound of formula (IVA)

wherein X − is an anion selected from the group consisting of a halide, an anion of a substituted or unsubstituted monocarboxylic acid, an anion of a substituted or unsubstituted dicarboxylic acid, an anion of a substituted or unsubstituted phosphate, an anion of a substituted or unsubstituted sulfate, an anion of a substituted or unsubstituted carbonate, and an anion of a substituted or unsubstituted carbamate;
(c) processing the compound of formula (IVA); and
(d) isolating the compound of formula (IVA).

10 . The method of claim 9 , wherein in oxidizing step (b) X − is an anion of a substituted or unsubstituted dicarboxylic acid.

11 . The method of claim 9 , wherein in oxidizing step (b) X − is a halide selected from fluoride, chloride, bromide, or iodide.

12 . The method of claim 11 , wherein in oxidizing step (b) X − is chloride.

13 . The method of claim 9 , wherein the oxidizing step (b) is carried out in the presence of a carbon-containing catalyst.

14 . The method of claim 13 , wherein the carbon-containing catalyst is activated carbon, optionally including a transition metal selected from the group consisting of palladium, platinum, ruthenium, rhodium, osmium, iridium, and combinations thereof.

15 . The method of claim 13 , wherein the compound of formula (IIIA) and the carbon-containing catalyst are present in a molar ratio of from about 10:1 to about 1:10.

16 . The method of claim 13 , wherein the oxidizing step (b) is carried out in the presence of an aqueous solution using a compound of formula Z + X − , wherein Z + is selected from the group consisting of a substituted or unsubstituted ammonium, a substituted or unsubstituted pyridinium, a substituted or unsubstituted pyrrolidinium, a substituted or unsubstituted imidazolium, and a substituted or unsubstituted triazolium, and wherein X − is defined as above.

17 . The method of claim 16 , wherein the aqueous solution comprises, in addition to water, an organic solvent.

18 . The method of claim 16 , wherein the compound of formula (IIIA) and the compound of formula Z + X − are present in a molar ratio of from about 1:5 to about 5:1.

19 . The method of claim 9 , further comprising the steps:
(e) when one or more of R 6 , R 7 or R 8 comprise a protecting group, deprotecting the compound of formula (IVA) to so as to produce the compound of formula (IA)

wherein Y, m, n, R 1 , R 2 , R 3 , R 4 , R 5 , and X − are defined as above; and
(f) isolating the compound of formula (IA).

20 . The method of claim 19 , wherein the deprotecting step (e) is carried out using a deprotecting agent selected from an acid or a base.

21 . The method of claim 19 , wherein each of R 6 , R 7 , and R 8 comprise an ester-type protecting group.

22 . The method of claim 19 , wherein at least two of R 6 , R 7 , and R 8 comprise an ester-type protecting group, and the deprotecting agent is a base.

23 . The method of claim 22 , wherein at least two of R 6 , R 7 , and R 8 comprise unsubstituted acetyl or unsubstituted benzoyl.

24 . The method of claim 19 , wherein the deprotecting step (e) is carried out in the presence of water, a protic solvent or aprotic solvent, or mixtures thereof.

25 . The method of claim 19 , wherein the reactants are subjected to mechanical grinding.

Assignees

• Univ Belfast

Inventors

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

Classifications

• C07H1/06

  Separation; Purification · CPC title

• Y02P20/582

  Recycling of unreacted starting or intermediate materials · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H19/04

  Heterocyclic radicals containing only nitrogen atoms as ring hetero atom · CPC title

• A23L33/10

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