IP Library › Granted Patent US 10,000,520

Granted Patent B2

US 10,000,520 · App. 15/461,126 · Granted Jun 19, 2018

B-vitamin and amino acid conjugates ofnicotinoyl ribosides and reduced nicotinoyl ribosides, derivatives thereof, and methods of preparation thereof

Inventors: Marie Eugenie Migaud (Lurgan, GB); Philip Redpath (Portadown, GB); Kerri Crossey (Magherafelt, GB); Richard Cunningham (Portadown, GB); Ryan Dellinger (Azusa, CA); Troy Rhonemus (Mission Viejo, CA); Sylesh Venkataraman (Irvine, CA); Brian Nettles (Irvine, CA)

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

C07H19/048 C07H1/00 C07H19/04

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Quick Facts

Patent No.: US 10,000,520
App. No.: 15/461,126
Granted: Jun 19, 2018
Kind: B2

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Abstract

The present disclosure provides nicotinate/nicotinamide riboside compounds or derivatives of formula (I): wherein X − , Z 1 , Z 2 , n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are described herein, reduced analogs thereof, and synthetic processes for the preparation thereof.

Claims (204)

1. A nicotinate/nicotinamide riboside compound or derivative of formula (I), or a salt, hydrate, or solvate thereof:

wherein X − as counterion is absent, or when X − is present, X − is selected from the group consisting of fluoride, chloride, bromide, iodide, formate, acetate, ascorbate, benzoate, carbonate, citrate, carbamate, formate, gluconate, lactate, methyl bromide, methyl sulfate, nitrate, phosphate, diphosphate, succinate, sulfate, trifluoromethanesulfonate, trichloromethanesulfonate, tribromomethanesulfonate, and trifluoroacetate;

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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 6 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

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 , and —CH 2 —CH 3 ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 1 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R B , —C(O)OR B , —C(O)NR B 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 2 -C 6 )alkylene-OR C ;

R 6 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , (C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R ) CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )allylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 7 and R 8 are independently selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl(C 1 -C 4 )alkyl, and substituted or unsubstituted heterocycle(C 1 -C 4 )alkyl; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, substituted heterocycle, substituted aryl(C 1 -C 4 )alkyl, and substituted heterocycle(C 1 -C 4 )alkyl 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

Y 1 and Y 2 are independently selected from the group consisting of hydrogen, sodium, potassium, lithium, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ; or, alternatively, Y 1 and Y 2 taken together are selected from the group consisting of sodium, potassium, lithium, magnesium, calcium, strontium, and barium;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

further provided that when n is 0, Z 2 is NH, and R 1 is hydrogen, then R 6 , R 7 , and R 8 are not all simultaneously hydrogen;

further provided that when n is 0, Z 2 is NH, and R 1 , R 2 , R 3 , R 4 , and R 5 are each hydrogen, then R 6 is not —C(O)R′ or —C(O)OR′ where R′ is alkyl, and each of R 7 and R 8 are not independently hydrogen, —C(O)R′, or —C(O)OR′, where R′ is alkyl;

further provided that when n is 0, Z 2 is NH, R 1 is (C 1 -C 8 )alkyl or (C 1 -C 8 )cycloalkyl, and R 2 , R 3 , R 4 , and R 5 are each hydrogen, then each of R 6 , R 7 , and R 8 are not independently hydrogen or —C(O)R′;

further provided that when n is 0, Z 2 is oxygen, R 1 is (C 1 -C 8 )alkyl, (C 1 -C 8 )cycloalkyl, aryl, or substituted aryl, and R 2 , R 3 , R 4 , and R 5 are each hydrogen, then R 6 , R 7 , and R 8 are not all simultaneously —C(O)R′;

further provided that when X— is absent, n is 0,Z2 is oxygen, R1 is hydrogen, R2, R3, and R5 are each hydrogen, and R4 is hydrogen or —(C1-C6)alkyl, then each of R6 and R7 is not independently hydrogen or —C(O)R′, where R′ is unsubstituted aryl, and R8 is not hydrogen.

2. A reduced nicotinate/nicotinamide riboside compound or derivative of formula (II), or a salt, hydrate, or solvate thereof:

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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 B 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 2 and R 3 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 4 is 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

wherein C* has an absolute configuration of R or S, or a mixture of R and S;

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

R 6 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 6 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 6 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and **H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , (C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

further provided that when n is 0 and Z 2 is oxygen, then R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are not all simultaneously hydrogen;

further provided that when n is 0, Z 2 is oxygen, R 1 is hydrogen or (C 1 -C 4 )alkyl, and R 2 , R 3 , R 4 , and R 5 are each hydrogen, then each of R 6 , R 7 , and R 8 is not —C(O)R′, —C(O)OR′, or —C(O)NHR′, where R′ is hydrogen, unsubstituted (C 1 -C 8 )alkyl, unsubstituted (C 1 -C 8 )cycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted aryl(C 1 -C 4 )alkyl, or unsubstituted heterocycle(C 1 -C 6 )alkyl.

3. A method of making a nicotinate/nicotinamide riboside compound or derivative of formula (I), or a salt, hydrate, or solvate thereof:

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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 B 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 6 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle, vitamin B ester, vitamin B2 ester, vitamin B6 ester, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 ), substituted (C 1 -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 8 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, halogen, —CN, —NO 2 , —C(O)R C , —C(O)R C , —C(O)NR C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)O(C 1 -C 8 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 8 )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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 8 )alkyl, —OC(O)O(C 1 -C 8 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 8 )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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 56 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 7 and R 8 independently selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl(C 1 -C 4 )alkyl, and substituted or unsubstituted heterocycle(C 1 -C 4 )alkyl; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, substituted heterocycle, substituted aryl(C 1 -C 4 )alkyl, and substituted heterocycle(C 1 -C 4 )alkyl 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

Y 1 and Y 2 are independently selected from the group consisting of hydrogen, sodium, potassium, lithium, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 5 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 8 )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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —SO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ; or, alternatively, Y 1 and Y 2 taken together are selected from the group consisting of sodium, potassium, lithium, magnesium, calcium, strontium, and barium;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

comprising the steps of:

(a) providing a riboside compound or derivative having formula (2), or a salt thereof;

wherein X′ is selected from fluoro, chloro, bromo, iodo, HCO 2 , acetoxy, propionoxy, butyroxy, glutamyloxy, aspartyloxy, ascorbyloxy, benzoxy, HOCO 2 , citryloxy, carbamyloxy, gluconyloxy, lactyloxy, succinyloxy, sulfoxy, trifluoromethanesulfoxy, trichloromethanesulfoxy, tribromomethanesulfoxy, and trifluoroacetoxy;

R 6 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); wherein the substituted pyridyl and substituted 1,4-dihydropyridyl are substituted with one to five substituents independently selected from the group consisting —(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(═NR B )NR B 2 , —OR, —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR 8 ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene OR C ;

R 7 and R 8 are independently selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)HR′, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl(C 1 -C 4 )alkyl, and substituted or unsubstituted heterocycle(C 1 -C 4 )alkyl; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, substituted heterocycle, substituted aryl(C 1 -C 4 )alkyl, and substituted heterocycle(C 1 -C 4 )alkyl 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

Y 1 and Y 2 are independently selected from the group consisting of hydrogen, sodium, potassium, lithium, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 5 )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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ; or, alternatively, Y 1 and Y 2 taken together are selected from the group consisting of sodium, potassium, lithium, magnesium, calcium, strontium, and barium;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

(b) treating the compound or derivative having formula (2), or salt thereof, with about one molar equivalent amount of a Lewis acid;

(c) treating the compound or derivative having formula (2), or salt thereof, and the Lewis acid with about one molar equivalent of a nicotinate/nicotinamide compound or derivative having formula (1), or a salt thereof;

wherein 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 1 -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, —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, and substituted heterocycle are substituted with one to five substituent 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 B 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

(d) reacting the riboside compound or derivative having formula (2), or salt thereof, and the Lewis acid with the nicotinate/nicotinamide compound or derivative having formula (1), or salt thereof so as to produce the compound or derivative of formula (I), or salt, hydrate, or solvate thereof;

(e) adding water to the riboside compound or derivative having formula (2), or salt thereof, the Lewis acid, the nicotinate/nicotinamide compound or derivative having formula (1), or salt thereof, and the compound or derivative of formula (I), or salt, hydrate, or solvate thereof;

(f) extracting the riboside compound or derivative having formula (2), or salt thereof, the Lewis acid, the nicotinate/nicotinamide compound or derivative having formula (1), or salt thereof, the compound or derivative of formula (I), or salt, hydrate, or solvate thereof, and the water, with organic solvent; and

(g) isolating the compound or derivative of formula (I), or salt, hydrate, or solvate thereof.

4. The method of claim 3 , wherein the Lewis acid is selected from the group consisting of BF 3 , TMSOTf, and SnCl 4 .

5. A method of making a nicotinate/nicotinamide riboside compound or derivative of formula (I), or a salt, hydrate, or solvate thereof;

wherein X − as counterion is absent, or when X − is present, X − is selected from the group consisting of fluoride, chloride, bromide, iodide, formate, acetate, ascorbate, benzoate, carbonate, citrate, carbamate, formate, gluconate, lactate, methyl bromide, methyl sulfate, nitrate, phosphate, diphosphate, succinate, trifluoromethanesulfonate, trichloromethanesulfonate, tribromomethanesulfonate, and trifluoroacetate;

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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , (C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene OR C ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 B 2 , —C(═NR B )NR 2 , —OR, —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 3 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 6 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, and substituted heterocycle are substituted with one to five substituents independently selected form 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —C 1 —NC 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

comprising the steps of:

(a) providing a nicotinate/nicotinamide riboside compound or derivative having formula (3), or a salt thereof;

wherein X − as counterion is absent, or when X − is present, X − is selected from the group consisting of fluoride, chloride, bromide, iodide, formate, acetate, ascorbate, benzoate, carbonate, citrate, carbamate, gluconate, lactate, methyl bromide, methyl sulfate, nitrate, phosphate, diphosphate, succinate, sulfate, trifluoromethanesulfonate, trichloromethanesulfonate, tribromomethanesulfonate, and trifluoroacetate;

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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 8 )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 B 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(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 C 2 , —C(═NR C NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 8 )alkylene-OR C ;

R 7 and R 8 are independently selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl(C 1 -C 4 )alkyl, and substituted or unsubstituted heterocycle(C 1 -C 4 )alkyl; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, substituted heterocycle, substituted aryl(C 1 -C 4 )alkyl, and substituted heterocycle(C 1 -C 4 )alkyl are substituted with one to five substituents independently selected from the group consisting of —(C 1 -C 8 )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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, and substituted heterocycle are substituted with one to five substitutents 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , (C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 9 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 8 )allylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

Y 1 and Y 2 are independently selected from the group consisting of hydrogen, sodium, potassium, lithium, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C , or, alternatively, Y 1 and Y 2 taken together are selected from the group consisting of sodium, potassium, lithium, magnesium, calcium, strontium, and barium;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

(b) treating the compound or derivative having formula (3), or salt thereof, with at least about one molar equivalent amount of one or more reagent(s);

(c) reacting the nicotinate/nicotinamide riboside compound or derivative having formula (3), or salt thereof, with the one or more reagent(s) so as to produce the compound or derivative of formula (I), or salt, hydrate, or solvate thereof;

(d) adding water to the nicotinate/nicotinamide riboside compound or derivative having formula (3), or salt thereof, the one or more reagent(s), and the compound or derivative of formula (I), or salt, hydrate, or solvate thereof;

(e) extracting the nicotinate/nicotinamide riboside compound or derivative having formula (3), or salt thereof, the one or more reagent(s), the compound or derivative of formula (I), or salt, hydrate, or solvate thereof, and the water, with organic solvent; and

(f) isolating the compound or derivative of formula (I), or salt, hydrate, or

solvate thereof.

6. A method of making a nicotinate/nicotinamide riboside compound or derivative of formula (I), or a salt, hydrate, or solvate thereof:

wherein X − as counterion is absent, or when X − is present, X − is selected from the group consisting of fluoride, chloride, bromide, iodide, formate, acetate, ascorbate, benzoate, carbonate, citrate, carbamate, gluconate, lactate, methyl bromide, methyl sulfate, nitrate, phosphate, diphosphate, succinate, sulfate, trifluoromethanesulfonate, trichloromethanesulfonate, tribromomethanesulfonate, and trifluoroacetate;

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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, and substituted heterocycle are substituted with one to five substituents independently selected from the group consisting —(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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

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 , and —CH 2 —CH 3 ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 B 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , (C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 6 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 8 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )allylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 7 and R 8 are independently selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl(C 1 -s)alkyl, and substituted or unsubstituted heterocycle(C 1 -C 4 )alkyl; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, substituted heterocycle, substituted aryl(C 1 -C 4 )alkyl, and substituted heterocycle(C 1 -C 4 )alkyl 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

(a) providing a reduced nicotinate/nicotinamide riboside compound or derivative of formula (II), or a salt, hydrate, or solvate thereof;

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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 B 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 4 is 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

wherein C* has an absolute configuration of R or S, or a mixture of R and S;

R 5 is 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 6 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycle, vitamin B ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 7 and R 8 are independently selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl(C 1 -C 4 )alkyl, and substituted or unsubstituted heterocycle(C 1 -C 4 )alkyl; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -C 8 )cycloalkyl, substituted aryl, substituted heteroaryl, substituted heterocycle, substituted aryl(C 1 -C 4 )alkyl, and substituted heterocycle(C 1 -C 4 )alkyl 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 8 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 8 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

(b) oxidizing a compound or derivative of formula (II), or a salt, hydrate, or solvate thereof, with at least about one molar equivalent amount of an oxidizing agent so as to produce the compound or derivative of formula (I), or salt, hydrate, or solvate thereof; and

7. The method of claim 6 , further comprising the steps of:

(a1) providing a reduced nicotinate/nicotinamide riboside compound or derivative having formula 4), or a salt thereof:

wherein 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 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , (C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

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 , —CH 2 —CH 3 ;

R B is 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, substituted or unsubstituted 1,4-dihydropyridyl, a radical of the compound of formula (I), and vitamin B7 ester (biotinyl); 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 C 2 , —C(═NR B )NR B 2 , —OR B , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR B 2 , —(C 1 -C 6 )alkylene-NR B 2 , —NR B 2 , —NR B C(O)R B , —NR B C(O)O(C 1 -C 6 )alkyl, —NR B C(O)NR B 2 , —NR B SO 2 NR B , —SR B , —S(O)R B , —SO 2 R B , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR B 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR B ;

R 4 is 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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

wherein C* has an absolute configuration of R or S, or a mixture of R and S;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -C 8 )cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, vitamin B1 ester, vitamin B2 ester, vitamin B6 ester, choline ester, biotin ester, vitamin A ester, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R 10 is selected from the group consisting of hydrogen, —C(O)R′, —C(O)OR′, —C(O)NHR′, —P(O)(OY 1 )(OY 2 ), —P(O)(OY 1 )(NHR″), substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , (C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene-OR C ;

R″ is selected from the group consisting of hydrogen, substituted or unsubstituted (C 1 -C 8 )alkyl, substituted or unsubstituted (C 1 -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, resveratrol ester, aryl(C 1 -C 4 )alkyl, heterocycle(C 1 -C 4 )alkyl, and —C**H—(R A )—CO 2 R B ; wherein the substituted (C 1 -C 8 )alkyl, substituted (C 1 -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 C 2 , —C(═NR C )NR C 2 , —OR C , —OC(O)(C 1 -C 6 )alkyl, —OC(O)O(C 1 -C 6 )alkyl, —OC(O)NR C 2 , —(C 1 -C 6 )alkylene-NR C 2 , —NR C 2 , —NR C C(O)R C , —NR C C(O)O(C 1 -C 6 )alkyl, —NR C C(O)NR C 2 , —NR C SO 2 NR C , —SR C , —S(O)R C , —SO 2 R C , —OSO 2 (C 1 -C 6 )alkyl, —SO 2 NR C 2 , —(C 1 -C 6 )perfluoroalkyl, and —(C 1 -C 6 )alkylene OR C ;

provided that when Z 2 is NH, the absolute configuration of C** is R or S, or a mixture of R and S;

(a2) treating the compound or derivative having formula (4), or salt thereof, with at least about 0.5 molar equivalent amount of one or more activated reagent(s);

(a3) reacting the reduced nicotinate/nicotinamide riboside compound or derivative having formula (4), or salt thereof, with the one or more activated reagent(s) so as to produce a reduced nicotinate/nicotinamide riboside compound or derivative of formula (II), or salt, hydrate, or solvate thereof;

(a4) adding water to the reduced nicotinate/nicotinamide riboside compound or derivative having formula (4), or salt thereof, the one or more activated reagent(s), and a compound or derivative of formula (II), or salt, hydrate, or solvate thereof;

(a5) extracting the reduced nicotinate/nicotinamide riboside compound or derivative having formula (4), or salt thereof, the one or more activated reagent(s), a compound or derivative of formula (II), or salt, hydrate, or solvate thereof, and the water with organic solvent; and

(a6) isolating a compound or derivative of formula (II), or salt, hydrate, or solvate thereof;

wherein steps (a1) through (a6) are performed sequentially before providing step (a).

8. A nicotinate/nicotinamide riboside compound or derivative of formula (I), or a salt thereof of claim 1 , selected from the group consisting of:

pterostilbene nicotinate riboside triflate, wherein R 1 is pterostilbenyl (4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl), n=0, Z 2 =oxygen, R 2 =R 3 =R 4 =R 5 hydrogen, X − =triflate (trifluoromethanesulfonate), R 6 =R 7 =R 8 =acetyl, or a salt thereof;

pterostilbene nicotinate riboside bromide, wherein R 1 is pterostilbenyl (4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl), n=0, Z 2 =oxygen, R 2 =R 3 =R 4 =R 5 =hydrogen, X − =bromide, R 6 =R 7 =R 8 =acetyl, or a salt thereof;

resveratrol trinicotinate riboside triflate, wherein R 1 is resveratryl (trans-3,5,4-trihydroxystilbenyl), n=0, Z 2 =oxygen, R 2 =R 3 =R 4 =R 5 =hydrogen, X − =triflate (trifluoromethanesulfonate), R 6 =R 7 =R 8 =acetyl, or a salt thereof;

nicotinamide N-tert-butyloxycarbonyl-tryptophan riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-tryptophan, or a salt thereof;

nicotinamide tryptophan riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =tryptophan, or a salt thereof;

nicotinamide N-tert-butyloxycarbonyl-isoleucine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-isoleucine, or a salt thereof;

nicotinamide isoleucine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =isoleucine, or a salt thereof;

nicotinamide N-tert-butyloxycarbonyl-alanine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-alanine, or a salt thereof;

nicotinamide alanine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =alanine, or a salt thereof;

nicotinamide N-tert-butyloxycarbonyl-phenylalanine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-phenylalanine, or a salt thereof;

nicotinamide phenylalanine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =phenylalanine, or a salt thereof;

nicotinamide N-tert-butyloxycarbonyl-valine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-valine, or a salt thereof;

nicotinamide valine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =valine, or a salt thereof;

nicotinamide N-tert-butyloxycarbonyl-methionine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 1 =hydrogen, R 6 =N-tert-butyloxycarbonyl-methionine, or a salt thereof;

nicotinamide methionine riboside chloride, wherein X − =chloride, R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =methionine, or a salt thereof;

2-bromoethyl nicotinate riboside triacetate triflate, wherein X − =triflate (trifluoromethanesulfonate), R 1 =2-bromoethyl, n=0, Z 2 =oxygen, R 2 =R 3 =R 4 =R 5 =hydrogen, R 6 =R 7 =R 8 =acetyl, or a salt thereof; and

choline nicotinate riboside triflate, wherein X − =triflate (trifluoromethanesulfonate), R 1 =choline, n=0, Z 2 =oxygen, R 2 =R 3 =R 4 =R 5 =R 6 =R 7 =R 8 =hydrogen.

9. A reduced nicotinate/nicotinamide riboside compound or derivative of formula (II), or a salt thereof of claim 2 , selected from the group consisting of:

reduced nicotinamide N-fluorenylmethyloxycarbonyl-tryptophan riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-fluorenylmethyloxycarbonyl-tryptophan, or a salt thereof;

reduced nicotinamide N-tert-butyloxycarbonyl-tryptophan riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-tryptophan, or a salt thereof;

reduced nicotinamide N-tert-butyloxycarbonyl-isoleucine riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-isoleucine, or a salt thereof;

reduced nicotinamide N-tert-butyloxycarbonyl-alanine riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-alanine, or a salt thereof;

reduced nicotinamide N-tert-butyloxycarbonyl-phenylalanine riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-phenylalanine, or a salt thereof,

reduced nicotinamide N-tert-butyloxycarbonyl-valine riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-valine, or a salt thereof;

reduced nicotinamide N-tert-butyloxycarbonyl-methionine riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-methionine, or a salt thereof; and

reduced nicotinamide N-tert-butyloxycarbonyl-leucine riboside, wherein R 1 =hydrogen, n=0, Z 2 =NH, R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =hydrogen, R 6 =N-tert-butyloxycarbonyl-leucine, or a salt thereof.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 28, 2017

From: MIGAUD, MARIE, DR.; REDPATH, PHILIP; CROSSEY, KERRI; CUNNINGHAM, RICHARD; DELLINGER, RYAN; RHONEMUS, TROY; VENKATARAMAN, SYLESH; NETTLES, BRIAN

To: CHROMADEX, INC.; THE QUEEN'S UNIVERSITY OF BELFAST

Reel/Frame 042187/0026 →

Continuity (2)

Provisional Application 62309273 · Mar 16, 2016

Related Publication 20170267709A1 · Sep 21, 2017

Cited By (4)

US 12,344,629 US 12,358,940 US 12,649,760 US 12,714,722