Granted Patent B2

US 12,195,494 · App. 18/237,503 · Granted Jan 14, 2025

Inventors: Marie Eugenie Migaud (Lurgan, GB); Philip Redpath (Firestone, CO); Kerri Crossey (Magherafelt, GB); Richard Cunningham (Portadown, GB); Aron Erickson (Berthoud, CO); Richard Nygaard (Longmont, CO); Amanda Storjohann (Westminster, CO)

Assignees: The Queen's University of Belfast; ChromaDex Inc.

C07H19/048C07D307/20C07H19/20C07B2200/13C07H19/04

Abstract

Claims (71)

1. A method of making a compound or derivative having formula (I-H), or salt, solvate, or prodrug thereof, wherein R 6 , R 7 and R 8 are each hydrogen:

wherein X − as counterion is absent, or when X − is present, X − is selected from the group consisting of a fluoride, chloride, bromide, iodide, formate, acetate, propionate, butyrate, glutamate, aspartate, ascorbate, benzoate, carbonate, citrate, carbamate, gluconate, lactate, succinate, sulfate, trifluoromethanesulfonate, trichloromethanesulfonate, tribromomethanesulfonate, malate, tartrate, glycolate, glucuronate, maleate, fumarate, pyruvate, anthranilate, 4-hydroxyl benzoate, phenylacetate, mandelate, palmoate, methanesulfonate, ethanesulfonate, benzenesulfonate, pantothenate, trifluoroacetate, trichloroacetate, tribromoacetate, 2-hydroxyethananesulfonyl, p-toluenesulfonyl, sulfanilate, cyclohexylaminosulfonate, stearate, alginate, beta-hydroxybutyrate, salicylate, galactarate, galacturonate, nitrate, and phosphate,

Z 1 and Z 2 are independently NH or oxygen;

n is 0 or 1;

R 1 is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 3 -C 8 ) cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, pterostilbene ester, resveratrol ester, aryl (C 1 -C 4 )alkyl, heterocycle (C 1 -C 4 )alkyl, —N(R A )—CO 2 R C , —N(R A )—CO 2 R B , —C**H—(R A )—NH 2 , and —C**H-(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 3 -C 8 ) cycloalkyl, substituted aryl, substituted heteroaryl, and substituted heterocycle are substituted with one to five substituents independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R C , —C(O)OR C , —C(O)NR2 C , -C(═NR C )NR 2 C , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 C , —(C 1 -C 6 )alkylene-NR 2 C , —NR 2 C , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR 2 C , —NR C SO 2 NR2 C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 C , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

wherein when R 1 is hydrogen, Z 2 is oxygen, and n is 0, the compound or derivative having formula (I-H) may optionally take the form of the carboxylate anion conjugate base species of the compound or derivative having formula (I-H), further optionally associated with a positively charged counterion selected from the group consisting of calcium, magnesium, potassium, sodium, zinc, and ammonium cations;

R A is selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(CH 2 ) 3 —NH-C(NH 2 )(═NH), —CH 2 C(═O)NH 2 , —CH 2 COOH, —CH 2 SH, —(CH 2 ) 2 C(═O)—NH 2 , (CH 2 ) 2 COOH, —CH 2 -(2-imidazolyl), —CH (CH 3 )-CH 2 —CH 3 , —CH 2 CH (CH 3 ) 2 , —(CH 2 ) 4 —NH 2 , (CH 2 ) 2 -S-CH 3 , phenyl, —CH 2 -phenyl, —CH 2 -OH, —CH (OH)-CH 3 , —CH 2 -(3-indolyl), —CH 2 -(4-hydroxyphenyl), —CH (CH 3 ) 2 , —NH 2 , and —CH 2 —CH 3 ;

each R B is independently hydrogen or —(C 1 -C 8 )alkyl;

each R C is independently selected from the group consisting of hydrogen, —(C 1 -C 8 )alkyl, substituted or unsubstituted pyridyl, and substituted or unsubstituted 1,4-dihydropyridyl;

wherein the substituted pyridyl and substituted 1,4-dihydropyridyl are substituted with one to five substituents independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R B , —C(O)OR B , —C(O)NR 2 B , -C(═NR B )NR 2 B , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 B , —(C 1 -C 6 )alkylene-NR 2 B , —NR 2 B , —NRBC(O)R B , —NRBC(O)O(C 1 -C 6 )alkyl, —NRBC(O)NR 2 B , —NR B SO 2 NR 2 B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 B , —(C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R C , —C(O)OR C , —C(O)NR 2 C , -C(═NR C )NR 2 C , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 C , —(C 1 -C 6 )alkylene-NR 2 C , —NR 2 C , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR 2 C , —NR C SO 2 NR 2 C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 C , (C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

provided that the absolute configuration of C** is R or S, or a mixture of R and S; comprising the steps of:

(a) providing a compound or derivative having formula (I), or a salt, solvate, or prodrug thereof:

wherein X − as counterion is absent, or when X − is present, X − is selected from the group consisting of a fluoride, chloride, bromide, iodide, formate, acetate, propionate, butyrate, glutamate, aspartate, ascorbate, benzoate, carbonate, citrate, carbamate, gluconate, lactate, succinate, sulfate, trifluoromethanesulfonate, trichloromethanesulfonate, tribromomethanesulfonate, malate, tartrate, glycolate, glucuronate, maleate, fumarate, pyruvate, anthranilate, 4-hydroxyl benzoate, phenylacetate, mandelate, palmoate, methanesulfonate, ethanesulfonate, benzenesulfonate, pantothenate, trifluoroacetate, trichloroacetate, tribromoacetate, 2-hydroxyethananesulfonyl, p-toluenesulfonyl, sulfanilate, cyclohexylaminosulfonate, stearate, alginate, beta-hydroxybutyrate, salicylate, galactarate, galacturonate, nitrate, and phosphate;

Z 1 and Z 2 are independently NH or oxygen;

n is 0 or 1;

R 1 is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 3 -C 8 ) cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, pterostilbene ester, resveratrol ester, aryl (C 1 -C 4 )alkyl, TMS, heterocycle (C 1 -C 4 )alkyl, —N(R A )—CO 2 R C , -N(R A )—CO 2 R B , —C**H—(R A )—NH 2 , and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 3 -C 8 ) cycloalkyl, substituted aryl, substituted heteroaryl, and substituted heterocycle are substituted with one to five substituents independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R C , —C(O)OR C , C(O)NR 2 C , -C(═NR C )NR 2 C , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 C , —(C 1 -C 6 )alkylene-NR 2 C , —NR 2 C , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR2 C , —NR C SO 2 NR 2 C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 C , —(C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

wherein when R 1 is hydrogen, Z 2 is oxygen, and n is 0, the compound or derivate having formula (I) may optionally take the form of the carboxylate anion conjugate base species of the compound or derivative having formula (I), further optionally associated with a positively charged counterion selected from the group consisting of calcium, magnesium, potassium, sodium, zinc, and ammonium cations;

R A is selected from the group consisting of —H, —(C 1 -C 6 )alkyl, (CH 2 ) 3 —NH-C(NH 2 )(═NH), —CH 2 C(═O)NH 2 , —CH 2 COOH, —CH 2 SH, —(CH 2 ) 2 C(═O)—NH 2 , (CH 2 ) 2 COOH, —CH 2 -(2-imidazolyl), —CH (CH 3 )-CH 2 —CH 3 , —CH 2 CH (CH 3 ) 2 , —(CH 2 ) 4-NH 2 , (CH 2 ) 2 -S-CH 3 , phenyl, —CH 2 -phenyl, —CH 2 -OH, —CH (OH)-CH 3 , —CH 2 -(3-indolyl), —CH 2 -(4-hydroxyphenyl), —CH (CH 3 ) 2 , —NH 2 , and —CH 2 —CH 3 ;

each R B is independently hydrogen or —(C 1 -C 8 )alkyl;

each R C is independently selected from the group consisting of hydrogen, —(C 1 -C 8 )alkyl, substituted or unsubstituted pyridyl, and substituted or unsubstituted 1,4-dihydropyridyl;

wherein the substituted pyridyl and substituted 1,4-dihydropyridyl are substituted with one to five substituents independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R B , —C(O)OR B , —C(O)NR 2 B , -C(═NR B )NR 2 B , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 B , —(C 1 -C 6 )alkylene-NR 2 B , —NR 2 B , —NRBC(O)R B , —NRBC(O)O(C 1 -C 6 )alkyl, —NRBC(O)NR 2 B , —NR B SO 2 NR 2 B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 B , —(C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R C , —C(O)OR C , —C(O)NR 2 C , -C(═NR C )NR 2 C , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 C , —(C 1 -C 6 )alkylene-NR 2 C , —NR 2 C , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR2 C , —NR C SO 2 NR 2 C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 C , (C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

each of R 6 , R 7 and R 8 is—C(O)R′;

R′ is substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 3 -C 8 ) cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;

provided that the absolute configuration of C** is R or S, or a mixture of R and S;

(b) treating the compound or derivative having formula (I), or salt, solvate, or prodrug thereof, with a protic solvent and a reagent selected from the group consisting of a (x≤20) molar equivalent amount of a Brønsted acid, and a (x<20) molar equivalent amount of an acyl chloride;

(c) processing the compound or derivative having formula (I), or salt, solvate, or prodrug thereof, the protic solvent, and the reagent so as to produce the compound or derivative having formula (I-H), or salt, solvate, or prodrug thereof, wherein R 6 , R 7 , and R 8 are each hydrogen; and

(d) isolating the compound or derivative having formula (I-H), or salt, solvate, or prodrug thereof, wherein R 6 , R 7 , and R 8 are each hydrogen.

2. The method of claim 1 , wherein the processing of step (c) is selected from the group consisting of batch processing, liquid-assisted mixing, milling, grinding, and extruding.

3. The method of claim 1 , wherein when the reagent of step (b) is Brønsted acid, the method further comprises the step of:

(c1) neutralizing the Brønsted acid using a base under controlled conditions; wherein the step (c1) is performed following step (c).

4. The method of claim 1 , further comprising the steps of:

(a1) providing a compound or derivative having formula (1), or a salt thereof, optionally wherein each R 1 is a TMS group:

wherein Z 1 and Z 2 are independently nitrogen or oxygen;

m is 1 or 2;

n is 0 or 1;

each R 1 is independently selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 3 -C 8 ) cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, pterostilbene ester, resveratrol ester, aryl (C 1 -C 4 )alkyl, heterocycle (C 1 -C 4 )alkyl, TMS, —N(R A )—CO 2 R C , —N(R A )—CO 2 R B , —C**H—(R A )—NH 2 , and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 3 -C 8 ) cycloalkyl, substituted aryl, substituted heteroaryl, and substituted heterocycle are substituted with one to five substituents independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R C , —C(O)OR C , —C(O)NR 2 C , -C(═NR C )NR 2 C , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR2 C , —(C 1 -C 6 )alkylene-NR2 C , —NR 2 C , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR2 C , —NR C SO 2 NR 2 C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 C , —(C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

wherein when each R 1 is hydrogen, Z 2 is oxygen, m is 1, and n is 0, the compound or derivative having formula (1) may optionally take the form of the carboxylate anion conjugate base species of the compound or derivative having formula (1), further optionally associated with a positively charged counterion selected from the group consisting of calcium, magnesium, potassium, sodium, zinc, and ammonium cations;

R A is selected from the group consisting of —H, —(C 1 -C 6 )alkyl, (CH 2 ) 3 —NH-C(NH 2 )(═NH), —CH 2 C(═O)NH 2 , —CH 2 COOH, —CH 2 SH, —(CH 2 ) 2 C(═O)—NH 2 , (CH 2 ) 2 COOH, —CH 2 -(2-imidazolyl), —CH (CH 3 )-CH 2 —CH 3 , —CH 2 CH (CH 3 ) 2 , —(CH 2 ) 4-NH 2 , (CH 2 ) 2 -S-CH 3 , phenyl, —CH 2 -phenyl, —CH 2 -OH, —CH (OH)-CH 3 , —CH 2 -(3-indolyl), —CH 2 -(4-hydroxyphenyl), —CH (CH 3 ) 2 , —NH 2 , and —CH 2 —CH 3 ;

each R B is independently hydrogen or —(C 1 -C 8 )alkyl;

each R C is independently selected from the group consisting of hydrogen, —(C 1 -C 8 )alkyl, substituted or unsubstituted pyridyl, and substituted or unsubstituted 1,4-dihydropyridyl; wherein the substituted pyridyl and substituted 1,4-dihydropyridyl are substituted with one to five substituents independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, CN, —NO 2 , —C(O)R B , —C(O)OR B , C(O)NR 2 B , -C(═NR B )NR 2 B , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 B , —(C 1 --NR 2 B , —NRBC(O)R B , —NRBC(O)O(C 1 -C 6 )alkyl, —NRBC(O)NR 2 B , -C 6 )alkylene-NR 2 B , NR B SO 2 NR 2 B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 B , —(C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R C , —C(O)OR C , —C(O)NR 2 C , -C(═NR C )NR 2 C , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR 2 C , —(C 1 -C 6 )alkylene-NR 2 C , —NR 2 C , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR 2 C , —NR C SO 2 NR 2 C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 C , (C 1 -C 6 ) perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

provided that the absolute configuration of C** is R or S, or a mixture of R and S;

(a2) treating the compound or derivative having formula (1), or salt thereof, optionally wherein each R 1 is a TMS group, with a molar equivalent amount of a compound or derivative having formula (2), or a salt thereof, in an organic solvent co-reagent:

wherein X′ is selected from the group consisting of fluoro, chloro, bromo, iodo, HCO 2 , acetoxy, propionoxy, butyroxy, glutamyloxy, aspartyloxy, ascorbyloxy, benzoyloxy, HOCO 2 , citryloxy, carbamyloxy, gluconyloxy, lactyloxy, succinyloxy, sulfoxy, trifluoromethanesulfonyloxy, trichloromethanesulfonyloxy, tribromomethanesulfonyloxy, malateoxy, tartaroxy, glycoloxy, glucoronoxy, maleateoxy, fumaroxy, pyruvoxy, anthraniloxy, 4-hydroxybenzoxy, phenylacetoxy, mandeloxy, pamoatoxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, panthothenoxy, trifluoroacetoxy, trichloroacetoxy, tribromoacetoxy, 2-hydroxyethananesulfonyloxy, p-toluenesulfonyloxy, sulfaniloxy, cyclohexylaminosulfonyloxy, stearoxy, alginoxy, beta-hydroxybutyroxy, salicyloxy, galactaroxy, and galacturonoxy, nitroxy, and phosphoryloxy;

each of R 6 , R 7 and R 8 is—C(O)R′;

R′ is substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 3 -C 8 ) cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;

(a3) processing the compound or derivative having formula (1), or salt thereof, optionally wherein each R 1 is a TMS group, the compound or derivative having formula (2), or salt thereof, and the organic solvent co-reagent so as to produce a compound or derivative having formula (I), or salt, solvate, or prodrug thereof, optionally wherein each R 1 is a TMS group;

(a4) isolating the compound or derivative having formula (I), or salt, solvate, or prodrug thereof, optionally wherein each R 1 is a TMS group;

wherein the steps (a1) to (a4) are performed sequentially, before step (a).

5. The method of claim 4 , wherein the compound or derivative having formula (1), or salt thereof, optionally wherein each R 1 is a TMS group, and the compound or derivative having formula (2), or salt thereof, in an organic solvent co-reagent, is further treated with a molar equivalent of a Lewis acid in step (a2).

6. The method of claim 4 , wherein the processing of step (a3) is selected from the group consisting of batch processing, liquid-assisted mixing, milling, grinding, and extruding.

7. The method of claim 1 , wherein the compound or derivative having formula (I), or salt, solvate, or prodrug thereof is nicotinamide riboside triacetate (NRTA) chloride, having formula (IX):

8. The method of claim 1 , wherein the compound or derivative having formula (I-H), or salt, solvate, or prodrug thereof, is nicotinamide riboside (NR) chloride, having formula (VII):

9. The method of claim 1 , wherein the compound or derivative having formula (I-H), or salt, solvate, or prodrug thereof;

wherein R 1 , R 2 , R 3 , R 4 , and R 5 are each hydrogen; Z 2 is independently NH or oxygen; and n is 0.

10. The method of claim 1 , wherein the alpha- and beta-anomers of the compound or derivative having formula (I), or salt, solvate, or prodrug thereof, are separately isolated, further comprising the steps of:

(b1) adding an organic solvent to the compound or derivative having formula (I), or salt, solvate, or prodrug thereof so as to precipitate the beta-anomer of the compound or derivative having formula (I), or salt, solvate, or prodrug thereof;

(b2) filtering the compound or derivative having formula (I), or salt, solvate, or prodrug thereof so as to isolate the beta-anomer of the compound or derivative having formula (I), or salt, solvate, or prodrug thereof; and

(b3) washing the beta-anomer of the compound or derivative having formula (I), or salt, solvate, or prodrug thereof, with the organic solvent;

wherein the steps (b1) to (b3) are performed sequentially, before step (b).

11. The method of claim 5 , wherein the Lewis acid is selected from the group consisting of trimethylsilyl trifluoromethanesulfonate, boron trifluoride, and tin (IV) chloride.

12. The method of claim 1 , wherein the compound having formula (I), a salt thereof, or a solvate thereof, is a beta-anomer.

13. The method of claim 9 , wherein the compound having formula (I), a salt thereof, or a solvate thereof, is a beta-anomer.

14. The method of claim 1 , wherein when the reagent is a Brønsted acid or an acyl chloride, the processing step (c) further comprises adding a base to effect X ion exchange.

15. The method of claim 1 , wherein when the reagent is a Brønsted acid or an acyl chloride, the processing step (c) further comprises X″ ion exchange.

16. The method of claim 9 , wherein when the reagent is a Brønsted acid or an acyl chloride, the processing step (c) further comprises X ion exchange.

17. The method of claim 1 , wherein the Brønsted acid is selected from the group consisting of HCl, HBr, and H 2 SO 4 .

18. The method of claim 1 , wherein the compound or derivative having formula (I-H), or salt, solvate, or prodrug thereof, is nicotinamide riboside (NR) malate.

19. The method of claim 1 , wherein the compound or derivative having formula (I-H), or salt, solvate, or prodrug thereof, is nicotinamide riboside (NR) tartrate.

Assignments (2)

Continuity (5)

References Cited (121)