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

Description

Nicotinamide Riboside Chloride is the chloride salt form of nicotinamide riboside(NR).NR is a new form pyridine-nucleoside of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide(NAD) or NAD+ . Nicotinamide riboside chloride is a crystal form of Nicotinamide riboside (NR) chloride. Nicotinamide riboside chloride increases NAD[+] levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside chloride is used in dietary supplements.

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.

Uses

Different sources of media describe the Uses of 23111-00-4 differently. You can refer to the following data:
1. Nicotinamide Riboside Chloride is a crystal form of Nicotinamide riboside (NR) chloride termed NIAGEN, generally recognized as safe (GRAS) for use in foods and in dietary supplements. Nicotinamide Riboside Chloride is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside is a newly discovered NAD (NAD+) precursor vitamin.
2. Nicotinamide riboside is involved in nicotinate and nicotinamide metabolism. Nicotinamide riboside was originally identified as a nutrient in milk and later discovered to be a NAD(+) precursor.Nicotinamide riboside (NR) is a naturally occurring vitamin B-3 present in the human diet that acts as an NAD+ precursor and is suggested to improve mitochondrial function and insulin sensitivity. NR acts via activation of the NAD+-dependent sirtuin enzyme family, thereby regulating oxidative metabolism. In vitro experiments of NR supplementation have shown its successful NAD+-restoring capability and subsequent increased oxidative gene expression in skeletal muscle cells. Results from 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.

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

• 13035-61-5 1,2,3,5-tetraacetylribose 
• 69688-12-6 N,N-bis(trimethylsilyl)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 
• 98-92-0 nicotinamide 
• 105499-44-3 2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride 
• 102276-96-0 trimethylsilyl N-trimethylsilylpyridine-3-carboximidate 
• 109527-15-3 5’,3‘,2’-tri-O-acetyl-1-β-D-ribofuranosylnicotinamide chloride 
• 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 
• 5991-01-5 2,3,5-(tri-O-benzoyl)-D-ribofuranosyl chloride 

Downstream Products

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

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.

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.

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.