23111-00-4

Basic information

• Product Name: Nicotinamide riboside chloride
• Synonyms: Nicotinamide riboside chloride;3-Carbamoyl-1-beta-D-ribofuranosylpyridinium chloride;3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium chloride;3-Carbamoyl-1-(β-D-ribofuranosyl)pyridinium chloride;Nicotinamide B-D Riboside Chloride(WX900111);Nicotinamide Riboside.Cl;Nicotimide riboside chloride
• CAS NO: 23111-00-4
• Molecular Formula: C₁₁H₁₅N₂O₅*Cl
• Molecular Weight: 290.7002
• EINECS: 200-184-4
• Product Categories: NMN;Food additive;API
• Mol File: 23111-00-4.mol
• Article Data: 19

Chemical Properties

• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Soluble to 100 mM in DMSO and to 100 mM in water
• CAS DataBase Reference: Nicotinamide riboside chloride(CAS DataBase Reference)
• NIST Chemistry Reference: Nicotinamide riboside chloride(23111-00-4)
• EPA Substance Registry System: Nicotinamide riboside chloride(23111-00-4)

Safety Data

• Hazardous Substances Data: 23111-00-4(Hazardous Substances Data)

Usage

Uses

1. Used in Dietary Supplements:
Nicotinamide riboside chloride is used as a dietary supplement for enhancing oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. It acts as a source of vitamin B3 (niacin) and is involved in nicotinate and nicotinamide metabolism.
2. Used in Mitochondrial Function and Insulin Sensitivity Improvement:
Nicotinamide riboside chloride is used as a nutrient to improve mitochondrial function and insulin sensitivity. It is a naturally occurring vitamin B-3 present in the human diet and acts as an NAD+ precursor, which is suggested to enhance these functions.
3. Used in Oxidative Gene Expression and Metabolic Flexibility:
Nicotinamide riboside chloride is used as a supplement to increase NAD+-restoring capability and subsequent oxidative gene expression in skeletal muscle cells. In vivo mouse models have shown improvements in insulin sensitivity and oxidative energy metabolism, including enhanced metabolic flexibility, increased aerobic exercise capacity, and indications of improved mitochondrial biogenesis.
4. Used in Nicotinic Acid and Nicotinamide Metabolism:
Nicotinamide riboside is used as a nutrient in the metabolism of nicotinic acid and nicotinamide, playing a role in the overall metabolic processes of the body.
5. Used as a NAD(+) Precursor:
Nicotinamide riboside is used as a NAD(+) precursor, which is essential for cellular energy production and various other biological processes. It acts via activation of the NAD+-dependent sirtuin enzyme family, thereby regulating oxidative metabolism.

History

Nicotinamide riboside (NR) was first described in 1944 as a growth factor, termed Factor V, for Haemophilus influenza, a bacterium that lives in and depends on blood. Factor V, purified from blood, was shown to exist in three forms: NAD+, NMN and NR. NR was the compound that led to the most rapid growth of this bacterium.Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase, which led several research groups to probe yeast NAD+ metabolism for genes and enzymes that might regulate lifespan. Biosynthesis of NAD+ in yeast was thought to flow exclusively through NAMN (nicotinic acid mononucleotide).When NAD+ synthase (glutamine-hydrolysing) was deleted from yeast cells, NR permitted yeast cells to grow. Thus, these Dartmouth College investigators proceeded to clone yeast and human nicotinamide riboside kinases and demonstrate the conversion of NR to NMN by nicotinamide riboside kinases in vitro and in vivo. They also demonstrated that NR is a natural product found in cow’s milk.

Biological Functions

Nicotinamide riboside (NR) is a newly discovered form of vitamin B3 that is found naturally in trace amounts in milk. No one really thought much about NR until scientists discovered that our bodies can convert NR into something called nicotinamide adenine dinucleotide (NAD+). And NAD+—at least for healthy-aging researchers—is kind of a big deal.NAD+ is a coenzyme found in all living cells, and it plays a vital role in energy metabolism and maintaining proper cell functioning. Levels of NAD+ also happen to decline significantly as we get older, and these declining levels apparently drive the aging process.

Biological Activity

Nicotinamide Riboside is an NAD+ precursor. It is a substrate for nicotinamide riboside kinases (NRK1/2). Nicotinamide Riboside shows neuroprotective effects in a mouse model of type 2 diabetes and improves mitochondrial function in muscle stem cells in aged mice. The compound also corrects non-alchoholic fatty liver disease phenotype induced by NAD+ deficiency or high-fat diet in mice. Orally bioavailable.

in vitro

Nicotinamide Riboside supplementation increases NAD+ content and sirtuin activity in cultured mammalian cells.

in vivo

Nicotinamide Riboside, a precursor to nicotinamide adenine dinucleotide(NAD), restores tissue NAD+ depletion induced by?acute kidney injury (AKI)?to that of the sham group, increases autophagy and sirtuin1 (Sirt1).

Synthetic route

1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofur-2-yl]-1,4-dihydropyridine-3-carboxamide (19132-12-8) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With ammonium chloride In water at 20℃; for 1h; Solvent;	100%
With 5%-palladium/activated carbon; ammonium chloride In isopropyl alcohol at 20℃; under 1500.15 Torr; for 20h; Reagent/catalyst; Temperature; Solvent; Pressure; Green chemistry;	89%

C12H17ClN2O6S → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
In methanol at 25℃; Solvent; Temperature;	90%

5’,3‘,2’-tri-O-acetyl-1-β-D-ribofuranosylnicotinamide chloride (109527-15-3) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With ammonia In methanol at -15 - -10℃; Temperature; Reagent/catalyst;	82%
With ethanol; ammonia at 10 - 20℃; for 3h;	78%
With methanol; ammonia at -5 - 0℃; for 12h; Large scale;	78%

C18H22NO9(1+)*Cl(1-) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With methanol; ammonia at 0℃; for 24h; Large scale;	67%

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium bromide (78687-39-5) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With Amberlite IRA-402 (Cl-Form) In water for 8h;	59%

3-carbamoyl-1-(tri-O-benzoyl-β-D-ribofuranosyl)-pyridinium; chloride (122620-02-4) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With sodium methylate In methanol at -5℃; for 24h;	52.6%
With methanol; ammonia
With ammonia In methanol at -32℃; for 120h;	0.28 g

3-carbamoyl-1-((2R,3R,4R,5R)-3,4-diacetoxy-5-(acetoxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium trifluoromethanesulfonate → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With hydrogenchloride In methanol; ethanol under 760.051 Torr; Cooling; Sealed tube;	2%
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate; sodium dithionite / water / 0.33 h / Inert atmosphere 2: methanol; sodium hydroxide / 0.5 h 3: ammonium chloride / water / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: ammonia / methanol / 24 h / -9 - -8 °C 2: hydrogenchloride / methanol / 8 h / -8 - 0 °C View Scheme

1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (6974-32-9) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen chloride; diethyl ether 2: acetonitrile 3: NH3; methanol View Scheme

2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride (105499-44-3) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile 2: NH3; methanol View Scheme
Multi-step reaction with 2 steps 1: 1,2-dichloro-ethane / 0 °C 2: ammonia / methanol / 16 h / 0 - 4 °C View Scheme

nicotinamide (98-92-0) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile 2: NH3; methanol View Scheme
Multi-step reaction with 4 steps 1.1: 1,1,1,3,3,3-hexamethyl-disilazane / 130 °C 1.2: 0.5 h 2.1: sodium hydrogencarbonate; sodium dithionite / water / 0.33 h / Inert atmosphere 3.1: methanol; sodium hydroxide / 0.5 h 4.1: ammonium chloride / water / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: acetonitrile 1.2: 0.5 h / 20 °C 2.1: methanol; sodium methylate / 0.5 h / 3 - 5 °C 3.1: sodium hydroxide; sodium chloride / water / 20 °C View Scheme

2,3,5-(tri-O-benzoyl)-D-ribofuranosyl chloride (5991-01-5) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile 2: NH3; methanol View Scheme

[(2R,5R)-3,4-diacetoxy-5-(3-carbamoyl-4H-pyridin-1-yl)tetrahydrofuran-2-yl]methyl acetate → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol; sodium hydroxide / 0.5 h 2: ammonium chloride / water / 1 h / 20 °C View Scheme

1,2,3,5-tetra-O-acetyl-D-ribofuranose (28708-32-9) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetonitrile 1.2: 0.5 h / 20 °C 2.1: methanol; sodium methylate / 0.5 h / 3 - 5 °C 3.1: sodium hydroxide; sodium chloride / water / 20 °C View Scheme

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium trifluoromethanesulfonate → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With sodium chloride; sodium hydroxide In water at 20℃;
With hydrogenchloride In methanol at -8 - 0℃; for 8h; Temperature;	16 g

C23H37N2O8Si2(1+)*Cl(1-) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With ammonia In methanol at -20℃;

C19H24NO9(1+)*Cl(1-) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With ammonia In methanol at 0 - 4℃; for 16h;

5’,3‘,2’-tri-O-acetyl-1-β-D-ribofuranosylnicotinamide chloride (109527-15-3) → nicotinamide riboside chloride salt (72521-19-8) + 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With ammonia In methanol at 0℃; for 3h; Inert atmosphere; Overall yield = 0.229 g;	A n/a B n/a

2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride (105499-44-3) + trimethylsilyl N-trimethylsilylpyridine-3-carboximidate (102276-96-0) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,2-dichloro-ethane / 0 °C 2: ammonia / methanol / -20 °C View Scheme

nicotinamide (98-92-0) → nicotinamide riboside chloride salt (72521-19-8) + 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1,1,1,3,3,3-hexamethyl-disilazane / 5 h / Reflux 2: calcium carbonate / chloroform / 40.5 h / 0 °C / Inert atmosphere 3: ammonia / methanol / 3 h / 0 °C / Inert atmosphere View Scheme

[(2R,3R,4R)-3,4-diacetoxy-5-chlorotetrahydrofuran-2-yl]methyl acetate (40554-98-1) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile / 0.33 h / 70 °C 2: hydrogenchloride / methanol / 12 h / Sealed tube View Scheme
Multi-step reaction with 2 steps 1: acetonitrile / 50 °C 2: hydrogenchloride / methanol / 12 h / Sealed tube View Scheme

2,3,5-Tris-O-acetyl-β-D-ribofuranosyl bromide (39925-22-9) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen bromide / acetonitrile; acetic acid / 15 h / 0 - 70 °C 2: hydrogen bromide / acetic acid; methanol / 48 h / 5 - 20 °C 3: Amberlite IRA-402 (Cl-Form) / water / 8 h View Scheme

N1-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-3-aminocarbonylpyridinium bromide (78687-38-4) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen bromide / acetic acid; methanol / 48 h / 5 - 20 °C 2: Amberlite IRA-402 (Cl-Form) / water / 8 h View Scheme

1-(β-D-ribofuranosyl)-nicotinamide (1341-23-7) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
With hydrogenchloride; pyrographite In methanol at -10 - -5℃; for 1h; Inert atmosphere;	8 g
With hydrogenchloride In methanol at 10 - 15℃; Large scale;	9.2 kg

N,N-bis(trimethylsilyl)nicotinamide (69688-12-6) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tin(IV) chloride / dichloromethane / 1.5 h / 55 °C 1.2: 0.75 h / 0 °C 2.1: methanol; propylamine / 22 h / -5 °C View Scheme

nicotinamide (98-92-0) + 1,2,3,5-tetraacetylribose (13035-61-5) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 0.33 h / 5 °C 1.2: 9 h / 5 - 30 °C 2.1: ammonia; methanol / 12 h / -5 - 0 °C / Large scale View Scheme

1,2,3,5-tetraacetylribose (13035-61-5) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile / 0.33 h / 20 °C / 760.05 Torr / Molecular sieve; Sealed tube 2: hydrogenchloride / methanol; ethanol / 760.05 Torr / Cooling; Sealed tube View Scheme

C11H15ClN2O6S → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4)

Conditions	Yield
In ethanol at 40℃; Solvent; Temperature; Large scale;	1.04 kg

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) + chlorophosphoric acid diphenyl ester (2524-64-3) → C23H24N2O8P(1+)*Cl(1-)

Conditions	Yield
With pyridine In acetonitrile at 0 - 5℃; for 12h; Solvent;	100%

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With trimethyl phosphite; trichlorophosphate at 0℃; for 12h; Inert atmosphere;	88.27%
Stage #1: 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) With Sodium trimetaphosphate; sodium hydroxide In water at 30℃; for 4h; pH=9; Stage #2: With hydrogenchloride In water at 10℃; Reagent/catalyst;	68%
With nitromethane; water; trichlorophosphate

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) + 2,2-dimethoxy-propane (77-76-9) → C14H19N2O5(1+)*HO4S(1-)

Conditions	Yield
With fuming sulphuric acid In acetonitrile at 0 - 20℃; for 2h; Inert atmosphere;	80%

L-Tartaric acid (87-69-4) + 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → nicotinamide-β-D-ribofuranoside L-hydrogen tartrate

Conditions	Yield
Stage #1: 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) With triethylamine under 760.051 Torr; Sealed tube; Stage #2: L-Tartaric acid With triethylamine In methanol at 0 - 20℃; under 760.051 Torr; pH=4 - 4.5; Sealed tube;	60%

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → 1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofur-2-yl]-1,4-dihydropyridine-3-carboxamide (19132-12-8)

Conditions	Yield
With sodium dithionate; sodium hydrogencarbonate at 20℃; for 3h; pH=8.1; Reagent/catalyst; Cooling with ice; Inert atmosphere;	55%

mesitaldehyde dimethylacetal (64761-29-1) + 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → C21H25N2O5(1+)*Cl(1-)

Conditions	Yield
With CSA In N,N-dimethyl-formamide at 20℃; for 4h;	26.6%

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → sodium β-nicotinamide mononucleotide

Conditions	Yield
Stage #1: 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) With trichlorophosphate for 1h; Milling; Stage #2: With sodium hydroxide In water pH=6; Reagent/catalyst;	23%
Multi-step reaction with 3 steps 1: pyridine / acetonitrile / 12 h / 0 - 5 °C 2: platinum(IV) oxide; hydrogen / deuteromethanol / 12 h 3: sodium carbonate / water View Scheme

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → 3-carbamoyl-1-((2R,3R,4S,5R)-5-((((((S)-1-(cyclohexyloxy)-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-3,4-dihydroxy-tetrahydrofuran-2-yl)pyridin-1-ium chloride

Conditions	Yield
Multi-step reaction with 3 steps 1.1: CSA / N,N-dimethyl-formamide / 4 h / 20 °C 2.1: tert-butylmagnesium chloride / tetrahydrofuran; 2-methyltetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere 3.1: hydrogenchloride / methanol; water; tetrahydrofuran / 1 h / 20 °C View Scheme

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydrofuran-2-yl)pyridin-1-ium chloride

Conditions	Yield
Multi-step reaction with 3 steps 1.1: CSA / N,N-dimethyl-formamide / 4 h / 20 °C 2.1: tert-butylmagnesium chloride / tetrahydrofuran; 2-methyltetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere 3.1: hydrogenchloride / methanol; water; tetrahydrofuran / 1 h / 20 °C View Scheme

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → C31H37N3O9P(1+)*Cl(1-)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: CSA / N,N-dimethyl-formamide / 4 h / 20 °C 2.1: tert-butylmagnesium chloride / tetrahydrofuran; 2-methyltetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere View Scheme

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → C36H45N3O9P(1+)*Cl(1-)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: CSA / N,N-dimethyl-formamide / 4 h / 20 °C 2.1: tert-butylmagnesium chloride / tetrahydrofuran; 2-methyltetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere View Scheme

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → C33H41N3O9P(1+)*Cl(1-)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: CSA / N,N-dimethyl-formamide / 4 h / 20 °C 2.1: tert-butylmagnesium chloride / tetrahydrofuran; 2-methyltetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere View Scheme

3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) (23111-00-4) → 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-((((((S)-1-methoxy-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydrofuran-2-yl)pyridin-1-ium chloride

Conditions	Yield
Multi-step reaction with 3 steps 1.1: CSA / N,N-dimethyl-formamide / 4 h / 20 °C 2.1: tert-butylmagnesium chloride / tetrahydrofuran; 2-methyltetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere 3.1: hydrogenchloride / methanol; water; tetrahydrofuran / 1 h / 20 °C View Scheme

Upstream product

• 109527-15-3 5’,3‘,2’-tri-O-acetyl-1-β-D-ribofuranosylnicotinamide chloride 
• 13035-61-5 1,2,3,5-tetraacetylribose 
• 98-92-0 nicotinamide 
• 69688-12-6 N,N-bis(trimethylsilyl)nicotinamide 
• 1341-23-7 1-(β-D-ribofuranosyl)-nicotinamide 
• 78687-38-4 N¹-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-3-aminocarbonylpyridinium bromide 
• 78687-39-5 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium bromide 
• 39925-22-9 2,3,5-Tris-O-acetyl-β-D-ribofuranosyl bromide 
• 40554-98-1 [(2R,3R,4R)-3,4-diacetoxy-5-chlorotetrahydrofuran-2-yl]methyl acetate 
• 105499-44-3 2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride 
• 102276-96-0 trimethylsilyl N-trimethylsilylpyridine-3-carboximidate 
• 445489-49-6 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium trifluoromethanesulfonate 
• 28708-32-9 1,2,3,5-tetra-O-acetyl-D-ribofuranose 
• 19132-12-8 1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofur-2-yl]-1,4-dihydropyridine-3-carboxamide 

Downstream Products

• 19132-12-8 1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofur-2-yl]-1,4-dihydropyridine-3-carboxamide 
• 1094-61-7 nicotinamide mononucleotide 

Relevant articles and documents

New crystalline salts of nicotinamide riboside as food additives

NR+ is a highly effective vitamin B3 type supplement due to its unique ability to replenish NAD+ levels. While NR+ chloride is already on the market as a nutritional supplement, its synthesis is challenging, expensive, and low yielding, making it cumbersome for large-scale industrial production. Here we report the novel crystalline NR+ salts, D/L/DL-hydrogen tartrate and D/L/DL-hydrogen malate. Their high-yielding, one-pot manufacture does not require specific equipment and is suitable for multi-ton scale production. These new NR+ salts seem ideal for nutritional applications due to their bio-equivalence compared to the approved NR+ chloride. In addition, the crystal structures of all stereoisomers of NR+ hydrogen tartrate and NR+ hydrogen malate and a comparison to the known NR+ halogenides are presented.

Preparation method β - nicotinamide ribose chloride

The invention belongs to the technical field of organic synthetic medicines, and particularly relates to a method for preparing β - nicotinamide ribose chloride. The method comprises the following steps: mixing a tetraacetylribose solution and a hydrogen chloride saturated solution, carrying out chlorination reaction to obtain a chlorination reaction solution, and I intermediate containing the structure shown first in the chlorination reaction solution. The chlorination reaction solution, the nicotinamide and first organic solvent are mixed to carry out nuclear saccharification reaction to obtain II intermediate with the structure shown 2nd. The II intermediate of the structure shown in Formula second the ammonia methanol solution and second organic solvent were mixed to conduct deacetyl reaction to obtain the β - nicotinamide ribose chloride. Β - nicotinamide ribose chloride prepared according to the preparation method provided by the invention has high yield.

Synthesis method of beta-nicotinamide riboside chloride

The invention discloses a synthesis method of beta-nicotinamide riboside chloride. According to the method, TMSCl is used as a chlorination reagent, boron trifluoride diethyl ether is used as a catalyst, and a glycosylation reaction of tetraacetylribose and nicotinamide is catalyzed. The reaction conditions are mild, and the product yield is high; the used reagents are low in cost, easy to obtainand suitable for industrial production; the reaction conditions are relatively safe and environmentally friendly, the reaction process is simple, and ion exchange reaction is not needed; a reaction product is relatively easy to purify and separate, and high quality of the product can be ensured; and the reagents used in the reaction process are lower in cost, and the production cost can be reduced.

NMN intermediate NR chloride synthesis method

The invention provides an intermediate synthesis method, and particularly relates to an NMN intermediate NR chloride synthesis method which is characterized in that D-ribose is used as a raw material, a certain temperature is controlled, an NR-sulfonyl hydrazine intermediate is prepared through a reaction with sulfonyl hydrazine under an acidic condition, chlorosuccinimide is further used for oxidative denitrification, and the NR-sulfonyl hydrazine intermediate reacts with nicotinate or nicotinamide, the NMN intermediate NR chloride is synthesized so that the cheaper source is provided for the starting material for synthesizing the NR chloride, the tedious step for synthesizing the NR chloride and the yield reduction caused by the low-efficiency ribose protection and deprotection step are avoided, the atom economy is high, and the industrial production is convenient.

METHODS OF SYNTHESIZING NICOTINAMIDE RIBOSIDE

Provided herein are efficient and scalable methods for the synthesis of nicotinamide riboside from riboside triacetate. Also provided are compositions comprising nicotinamide riboside, and therapeutic methods employing nicotinamide riboside.

Efficient synthesis method of nicotinamide riboside (NR) chloride

The invention discloses an efficient synthesis method of a nicotinamide riboside (NR) chloride. An acetyl-protected compound A on ribose ring hydroxyl is used as a raw material and oxidized directly to obtain a compound B, and acetyl is removed to obtain the NR chloride. The efficient synthesis method comprises the following synthesis steps: 1) adding the compound A to an autoclave, adding ammonium chloride, platinum carbon and ethanol, introducing oxygen, and carrying out stirring at room temperature until reaction ends; 2) recovering the platinum carbon by filtration, removing a solvent under reduced pressure, adding absolute ethyl alcohol, carrying out cooling to precipitate a white solid, and performing filtration and drying to obtain the compound B; and 3) adding the compound B in a three-neck bottle to be dissolved in ethanol, introducing ammonia, keep the temperature, cooling a reaction solution to precipitate a solid after the reaction, and performing filtration and drying to obtain the NR chloride. Oxidation is carried out after the ribose hydroxyl is protected by the acetyl, side reaction is reduced, so that the oxidation yield is greatly increased, meanwhile, the oxidation reaction is conducted with an oxygen pressurization manner, and the reaction efficiency is greatly improved.

Synthesis method of beta-nicotinamide mononucleotide

The invention discloses a synthesis method of beta-nicotinamide mononucleotide, and relates to the technical field of drug synthesis. The synthesis method mainly comprises the following steps of S1, mixing and reacting nicotinamide, hexamethyldisilazane and a catalyst I in a reaction kettle to obtain silanization-protected nicotinamide; S2, adding tetraacetyl ribose, a solvent, a catalyst II and methanol for reaction so as to generate nicotinamide triacetyl riboside; S3, adding methanol and n-propylamine to generate nicotinamide riboside; S4, adding trimethyl phosphate and phosphorus oxychloride to generate beta-nicotinamide mononucleotide; and S5, separating and purifying the beta-nicotinamide mononucleoside acid. According to the invention, a plurality of continuous steps are controlledto be carried out in one reaction container, and the steps of separating and purifying an intermediate are avoided, so that the method has the advantages of high yield and high production efficiency.

Organic acid salt of nicotinamide ribose and composition and method of making same

The invention belongs to the technical field of medicines, and discloses an organic acid salt of nicotinamide ribose, the organic acid is selected from malic acid, malic acid, royal jelly acid and thelike, and the molar ratio of nicotinamide ribose to the organic acid is 1: 2 or 1: 1. The invention also discloses a composition compounded by the organic acid salt of nicotinamide ribose and a carrier, wherein the carrier is selected from nicotinic acid, glutamic acid, royal jelly acid, nervonic acid, microcrystalline cellulose or apple vinegar powder. According to the invention, organic acids with stronger acidity are adopted, and the organic acids and nicotinamide ribose form tight ion pairs, so that certain hydrophobicity is obtained and the stability of nicotinamide ribose is improved; the carrier can prevent water from permeating, and the stability of the organic acid salt to water is improved.

Crystal form 1A and crystal form 1B of beta-nicotinamide ribose chloride and preparation method of crystal form 1A and crystal form 1B

The invention discloses a crystal form 1A and a crystal form 1B of beta-nicotinamide ribose chloride and preparation methods of the crystal form 1A and the crystal form 1B. In an X-ray powder diffraction pattern, the crystal form 1A has diffraction peaks with 2 theta of 13.0+/-0.2 degrees, 14.0+/-0.2 degrees, 23.8+/-0.2 degrees, 24.5+/-0.2 degrees and 25.4+/-0.2 degrees. In an X-ray powder diffraction pattern, the crystal form 1B has diffraction peaks with 2 theta of 5.0+/-0.2 degrees, 15.6+/-0.2 degrees, 21.6+/-0.2 degrees and 26.4+/-0.2 degrees. These two crystal forms of nicotinamide ribosehave more advantageous properties including substance morphology, stability (e.g., low content of solvent residue, low hygroscopicity, storage stability, polymorph transformation stability), solubility, chemical purity, and the like. The change of the properties is more beneficial to industrial production of high-purity nicotinamide ribose, and a wide space is provided for development of dosage forms of nicotinamide ribose.

Novel synthesis method of nicotinamide ribose

The invention discloses a novel synthesis method of nicotinamide ribose. According to the method, 2,3,4,5-tetrabenzoyloxy ribose is added into an alcoholic solution; acetyl chloride is dropwise added;chlorination reaction is performed; a chlorination product and nicotinamide are condensed; benzoyl is removed from a condensation product in sodium methoxide; stirring and purification are performedthrough an organic solvent; and crystallization is performed to obtain a finished product. The novel synthesis method has the advantages that the 2,3,4,5-tetrabenzoyloxy ribose is used as a starting material; ribose 2-benzoyl is selectively chloridized by the acetyl chloride; a product with beta-nicotinamide riboside as a main ingredient is generated; a catalyst is common and easy to obtain; the cost can be effectively reduced; the reaction design ingredients are simple; post treatment is simple; after deprotection, a protective agent and alpha impurities are removed by the organic solvent; and the high-purity finished product can be obtained through recrystallization.