1094-61-7

Basic information

• Product Name: BETA-NICOTINAMIDE MONONUCLEOTIDE
• Synonyms: BETA-NMN;BETA-NICOTINAMIDE MONONUCLEOTIDE;BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE;NMN;NICOTINAMIDE-1-IUM-1-BETA-D-RIBOFURANOSIDE 5'-PHOSPHATE;NICOTINAMIDE RIBOTIDE;NICOTINAMIDE MONONUCLEOTIDE;3-(aminocarbonyl)-1-(5-O-phosphonato-beta-D-ribofuranosyl)pyridinium
• CAS NO: 1094-61-7
• Molecular Formula: C₁₁H₁₅N₂O₈P
• Molecular Weight: 334.22
• EINECS: 214-136-5
• Product Categories: Amines;Aromatics;Bases & Related Reagents;Intermediates & Fine Chemicals;Nicotine Derivatives;Nucleotides;Pharmaceuticals;nicotinamide mononucleotide
• Mol File: 1094-61-7.mol

Chemical Properties

• Melting Point: 166 °C(dec.)
• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: g/cm³
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly, Heated), Methanol (Slightly), Water (Slightly)
• Stability: Very Hygroscopic
• Merck: 13,6697
• BRN: 3570187
• CAS DataBase Reference: BETA-NICOTINAMIDE MONONUCLEOTIDE(CAS DataBase Reference)
• NIST Chemistry Reference: BETA-NICOTINAMIDE MONONUCLEOTIDE(1094-61-7)
• EPA Substance Registry System: BETA-NICOTINAMIDE MONONUCLEOTIDE(1094-61-7)

Safety Data

• WGK Germany: 3
• F: 8-10-21
• Hazardous Substances Data: 1094-61-7(Hazardous Substances Data)

Usage

Chemical Properties

White to Yellowish lyophilized powder

Uses

β-Nicotinamide mononucleotide (NMN) is used to study binding motifs within RNA aptamers and ribozyme activation processes involving β-nicotinamide mononucleotide (β-NMN)-activated RNA fragments. NMN is a nucleotide derived from ribose and nicotinamide. Niacinamide (nicotinamide,) is a derivative of vitamin B3, also known as niacin.) As a biochemical precursor of NAD+, it may be useful in the prevention of pellagra.β-Nicotinamide mononucleotide is an intermediate in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to generate β-NMN, which is subsequently converted to NAD+ by β-NMN adenyltransferase.At 50-100 μM, β-NMN has been used to enhance NAD biosynthesis and glucose-stimulated insulin secretion in a Nampt+/- mouse model of metabolic disease, demonstrating a role for Nampt in β cell function.Furthermore, at 500 mg/kg/day, it has been shown to ameliorate glucose intolerance in high-fat diet-induced type 2 diabetes mice by restoring NAD+ levels.

Preparation

β-Nicotinamide mononucleotide is a NAD+intermediate. In recent years, the relation of NAD+metabolism and aging-associated disease is attracting attention from various research fields. Synthesis of β-nicotinamide mononucleotide (NMN) A solution of NAD (3.5 g, 5.28 mmol) and ZrCl4(6.15 g, 26.4 mmol) in 500 ml water was stirred at 50°C for 30 min. The hydrolysis was monitored by TLC (SiO2EtOH/ 1 M NH4Ac [7 : 3]). The reaction was quenched with 245mL of a 0.5 M solution of Na3PO4. After adjusting to pH 7 with a 2 M solution of HCl, a white precipitate was formed. The suspension was centrifuged 8 min,1,000rpm, the supernatant was collected and the pellet was washed two times with 200 mL water. The combined supernatants wereconcentrated to 1/3 of its volume on a rotary evaporator. The remaining solution was purified with a column filled with Dowex 50WX8 (100-200 mesh, H+-Form, column-material: 2.5 x 30 cm). The column was loaded with 1.5 L5 % HCl and equilibrated with1.5L millipore water until pH 5 was reached. 100 mL of the concentrated solution was loaded on the ion exchange column and eluted with Milliporewater. The first cleavage product eluted was NMN (615 mg, 1.84 mmol,yield:35 %) and yielded a colorless solid after evaporation of the solvent, followed by AMP. 1H NMR (500MHz, D2O)δ: 9.48 (s, 1 H), 9.31 (d,J= 6.2 Hz, 1 H), 9.00 (d,J= 8.2 Hz, 1 H), 8.32 (dd,J= 8.2, 6.2 Hz, 1 H), 6.24 (d,J=5.4 Hz, 1 H), 4.68-4.64 (m, 1 H), 4.58 (t, 1 H), 4.48-4.45 (m, 1 H), 4.36–4.14 (m,J= 12.0, 2 H). 13C NMR (75 MHz, d2o) δ: 165.50, 145.65, 142.15, 139.53, 133.62, 128.19, 99.65, 87.18, 87.06, 77.42, 70.71, 63.89, 63.82. 31P NMR (202 MHz, D2O)δ:-0.03

Definition

ChEBI: β-Nicotinamide Mononucleotide is a condensation product of nicotinamide and ribose 5-phosphate, in which the nitrogen of nicotinamide is linked to the (β) c-l of the ribose. NMN zwitterion is a nicotinamide mononucleotide. It has a role as an Escherichia coli metabolite and a mouse metabolite. It is a conjugate base of a NMN(+). It is a conjugate acid of a NMN(-).

Application

β-Nicotinamide mononucleotide (NMN) is a product of the extracellular Nicotinamide phosphoribosyltransferase (eNAMPT) reaction and a key NAD+ intermediate. It ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice . It also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. It is used to study binding motifs within RNA aptamers and ribozyme activation processes involving β-nicotinamide mononucleotide (β-NMN)-activated RNA fragments.

General Description

β-Nicotinamide mononucleotide (β-NMN) is an intermediate in the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed biosynthesis of nicotinamide adenine dinucleotide (NAD+). NAMPT mediates the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to produce β-NMN. β-NMN adenyltransferase subsequently converts β-NMN to NAD+.

in vitro

β-nicotinamide mononucleotide has several beneficial pharmacological activities. Mostly mediated by its involvement in NAD+ biosynthesis, the pharmacological activities of NMN include its role in cellular biochemical functions, cardioprotection, diabetes, Alzheimer's disease, and complications associated with obesity.The intracellular NAD+ levels are significantly decreased by knockdown or knockout of Nampt (Nampt KD or Nampt KO) or treatment with Nampt inhibitor FK866, whereas NAD+ levels are dramatically increased by supplement of NAD+ precursors NAM or NMN (0.5–1 mM). NAD+ precursor NMN treatment inhibited CD8+ T cells activation and function.

in vivo

β-Nicotinamide mononucleotide (500 mg/kg; i.p.; 3 times per week for 7-10 week) prevents mtDNA damage and Dox-induced cardiac dysfunction.Nampt KO markedly inhibits tumor progression, whereas Nampt metabolite β-Nicotinamide mononucleotide (300 mg/kg body weight; i.p.; once every two days for 2 weeks) significantly promotes tumor growth in C57BL/6 mice (bearing wildtype Hepa1-6 cells). The reduction and increase in NAD+ level of respective Nampt KO and β-Nicotinamide mononucleotide-treated tumors are confirmed.β-nicotinamide mononucleotide ameliorates glucose intolerance by restoring NAD(+) levels in HFD-induced T2D mice. β-nicotinamide mononucleotide also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation.

Purification Methods

Purify NMN by passage through a column of Dowex-1 (Clform) and washing with H2O until no absorbance is observed at 260 nm. The tubes containing NMN are pooled, adjusted to pH 5.5-6 and evaporated in vacuo to a small volume. This is adjusted to pH 3 with dilute HNO3 in an ice-bath and treated with 20volumes of Me2CO at 0-5o. The heavy white precipitate is collected by centrifugation at 0o. It is best stored wet and frozen or it can be dried to give a gummy residue. It has max 266nm ( 4,600) and min 249nm ( 3600) at pH 7.0 (i.e. no absorption at 340nm). It can be estimated by reaction with CNor hydrosulfite which form the 4-adducts (equivalent to NADH) which have UV max 340nm ( 6,200). Thus after reaction, an OD340 of one is obtained from a 0.1612mM solution in a 1cm path cuvette. [Plaut & Plaut Biochemical Preparations 5 56 1957, Maplan & Stolzenbach Methods Enzymol 3 899 1957, Kaplan et al. J Am Chem Soc 77 815 1955, Beilstein 22/2 V 168.]

InChI:InChI=1/C11H15N2O8P/c12-10(16)6-2-1-3-13(4-6)11-9(15)8(14)7(21-11)5-20-22(17,18)19/h1-4,7-9,11,14-15H,5H2,(H3-,12,16,17,18,19)/t7-,8-,9-,11-/m1/s1

Synthetic route

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 bromide (78687-39-5) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With trimethyl phosphite; trichlorophosphate at -5 - 0℃; for 7h;	80%
With trimethyl phosphite; trichlorophosphate at 0℃; for 4h;	64%

(3,4-dihydroxy-5-(3-(ethoxycarbonyl)pyridin-1-ium-1-yl)tetrahydrofuran-2-yl)methyl hydrogen phosphate → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With ammonia In acetonitrile at -5 - 5℃; for 1h;	80%

NAD (53-84-9) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With ethylenediaminetetraacetic acid; ammonium acetate; zirconium(IV) chloride In ethanol at 50℃; for 0.5h; pH 5;	70%
With water; zirconium(IV) chloride at 80℃; for 0.5h; Reagent/catalyst;

C23H24N2O8P(1+)*Cl(1-) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With platinum(IV) oxide; hydrogen In deuteromethanol for 12h; Reagent/catalyst;	64%

1-(β-D-ribofuranosyl)-nicotinamide (1341-23-7) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With trichlorophosphate In tetrahydrofuran at 0 - 20℃; for 12h;	56%

3-carbamoyl-1-(2,4-dinitrophenyl)pyridinium chloride (53406-00-1) + ribose 5-phosphate bis(cyclohexylammonium) salt (87763-86-8) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With ammonia 1.) -60 deg C, 36 h; r.t., 1 h; 2.) methanol, ethylene glycol (1:1), 4 deg C, 11 h;	35%

nicotinamide (98-92-0) + 5-phosphoribosyl-1-pyrophosphate (97-55-2, 7540-64-9, 99945-37-6, 130384-52-0) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Enzym aus Erythrocyten;

3-carbamoyl-1-(2,4-dinitrophenyl)pyridinium chloride (53406-00-1) + phosphoribosylamine (14050-66-9) → nicotinamide mononucleotide (1094-61-7) + α-nicotinamide mononucleotide (7298-94-4) + 2,4-Dinitroanilin (97-02-9)

Conditions	Yield
In methanol at 5℃; for 14h; Yield given;
In methanol at 5℃; for 14h;

β-NAD → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
enzymatische Spaltung;

N1-(2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl)-3-aminocarbonylpyridinium bromide (18784-01-5) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH3 / methanol 2: 80 percent / POCl3, PO(OMe)3 / 7 h / -5 - 0 °C View Scheme
Multi-step reaction with 2 steps 1: 55 percent / NH3 / methanol / 72 h / -18 °C 2: 64 percent / Phosphoryl chloride, trimethyl phosphate / 4 h / 0 °C View Scheme

N1-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-3-aminocarbonylpyridinium bromide (78687-38-4) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / NH3 / methanol / 20 h / -5 - -3 °C 2: 80 percent / POCl3, PO(OMe)3 / 7 h / -5 - 0 °C View Scheme

adenosine 5'-monophosphate (47287-36-5, 119923-66-9) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / 1.) H(+), H2O / 1.) 100 deg C, 6 min; 2.) 0 deg C 2: 35 percent / NH3 / 1.) -60 deg C, 36 h; r.t., 1 h; 2.) methanol, ethylene glycol (1:1), 4 deg C, 11 h View Scheme

1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (6974-32-9) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: HBr / CH2Cl2 / 3 h / -20 °C 2: liquid sulphur dioxide 3: 55 percent / NH3 / methanol / 72 h / -18 °C 4: 64 percent / Phosphoryl chloride, trimethyl phosphate / 4 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogen chloride; diethyl ether 2: acetonitrile 3: NH3; methanol 4: POCl3; nitromethane; H2O View Scheme

2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (22860-91-9) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: liquid sulphur dioxide 2: 55 percent / NH3 / methanol / 72 h / -18 °C 3: 64 percent / Phosphoryl chloride, trimethyl phosphate / 4 h / 0 °C View Scheme

2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride (105499-44-3) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetonitrile 2: NH3; methanol 3: POCl3; nitromethane; H2O View Scheme

nicotinamide (98-92-0) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetonitrile 2: NH3; methanol 3: POCl3; nitromethane; H2O View Scheme
Multi-step reaction with 3 steps 1: trimethylsilyl trifluoromethanesulfonate / tetrahydrofuran / 12 h / 0 - 20 °C 2: sodium ethanolate / ethanol / 1 h / -5 - 5 °C 3: trichlorophosphate / tetrahydrofuran / 12 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: ammonium sulfate / 8 h / 125 °C 2.1: tin(IV) chloride / dichloromethane / 1.5 h / 55 °C 2.2: 0.75 h / 0 °C 3.1: methanol; propylamine / 22 h / -5 °C 4.1: trimethyl phosphite; trichlorophosphate / 12 h / 0 °C / Inert atmosphere View Scheme

5’,3‘,2’-tri-O-acetyl-1-β-D-ribofuranosylnicotinamide chloride (109527-15-3) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH3; methanol 2: POCl3; nitromethane; H2O View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride / methanol / 12 h / Sealed tube 2: trichlorophosphate View Scheme

3-carbamoyl-1-(tri-O-benzoyl-β-D-ribofuranosyl)-pyridinium; chloride (122620-02-4) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH3; methanol 2: POCl3; nitromethane; H2O View Scheme

2,3,5-(tri-O-benzoyl)-D-ribofuranosyl chloride (5991-01-5) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetonitrile 2: NH3; methanol 3: POCl3; nitromethane; H2O View Scheme

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

Conditions	Yield
With trimethyl phosphite; trichlorophosphate at -5 - 0℃; for 12h; Inert atmosphere;

pentasodium 5-phosphoribosyl 1-pyrophosphate + nicotinamide (98-92-0) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With nicotinamide phosphoribosyltransferase; tris hydrochloride; ATP; magnesium chloride; D,L-dithiothreitol; bovine serum albumin In water at 37℃; Kinetics; Enzymatic reaction;

NAD (53-84-9) → nicotinamide mononucleotide (1094-61-7) + adenosine 5'-diphosphate (58-64-0) + adenosine (58-61-7)

Conditions	Yield
With water; zirconium(IV) oxide at 80℃; for 48h;

[(2R,3R,4R)-3,4-diacetoxy-5-chlorotetrahydrofuran-2-yl]methyl acetate (40554-98-1) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetonitrile / 0.33 h / 70 °C 2: hydrogenchloride / methanol / 12 h / Sealed tube 3: trichlorophosphate View Scheme
Multi-step reaction with 3 steps 1: acetonitrile / 50 °C 2: hydrogenchloride / methanol / 12 h / Sealed tube 3: trichlorophosphate View Scheme

3-carbamoyl-1-((2R,3R,4R,5R)-3,4-diacetoxy-5-(acetoxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium trifluoromethanesulfonate → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonia / methanol / 24 h / -9 - -8 °C 2: hydrogenchloride / methanol / 8 h / -8 - 0 °C 3: trimethyl phosphite; trichlorophosphate / 24 h / -10 - -7 °C View Scheme

nicotinamide adenine dinucleotide (76961-04-1) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With zirconium(IV) chloride In water at 50℃; for 1h;

nicotinamide (98-92-0) + 5-phospho-α-D-ribosyl 1-pyrophosphate → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
With tris(3-hydroxypropyl)phosphine; nicotinamide phosphoribosyltransferase; tris hydrochloride; ATP; magnesium chloride In water at 37℃; pH=7.5; Kinetics; Reagent/catalyst; Enzymatic reaction;

1,2,3,5-tetraacetylribose (13035-61-5) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trimethylsilyl trifluoromethanesulfonate / tetrahydrofuran / 12 h / 0 - 20 °C 2.1: ammonia / 1 h / -5 - 5 °C 2.2: 1 h / -5 - 5 °C 3.1: trichlorophosphate / tetrahydrofuran / 12 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: trimethylsilyl trifluoromethanesulfonate / tetrahydrofuran / 12 h / 0 - 20 °C 2: sodium ethanolate / ethanol / 1 h / -5 - 5 °C 3: trichlorophosphate / tetrahydrofuran / 12 h / 0 - 20 °C View Scheme

3-pyridinecarboxylic acid ethyl ester (614-18-6) → nicotinamide mononucleotide (1094-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trimethylsilyl trifluoromethanesulfonate / tetrahydrofuran / 12 h / 0 - 20 °C 2.1: ammonia / 1 h / -5 - 5 °C 2.2: 1 h / -5 - 5 °C 3.1: trichlorophosphate / tetrahydrofuran / 12 h / 0 - 20 °C View Scheme

L-valine (72-18-4) + nicotinamide mononucleotide (1094-61-7) → (S)-1-carboxy-2-methypropan-1-aminium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; pH=Ca. 3.8 - 4;	100%

nicotinamide mononucleotide (1094-61-7) + L-histidine (71-00-1) → (S)-1-carboxy-2-(1H-imidazol-4-yl)ethanaminium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; pH=Ca. 6 - 6.2;	100%

L-threonine (72-19-5) + nicotinamide mononucleotide (1094-61-7) → (1S,2R)-1-carboxy-2-hydropropan-1-aminium ((2R,3R,4S,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; pH=Ca. 3.9 - 4.4;	100%

nicotinamide mononucleotide (1094-61-7) + L-proline (147-85-3) → (S)-2-carboxypyrrolidin-1-ium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; pH=Ca. 3.3 - 3.9;	100%

L-lysine (56-87-1) + nicotinamide mononucleotide (1094-61-7) → (S)-5-amino-5-carboxypentan-1-aminium ((2R,3R,4S,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; pH=Ca. 6 - 6.2;	100%

L-Aspartic acid (56-84-8) + nicotinamide mononucleotide (1094-61-7) → (S)-1,2-dicarboxyethan-1-aminium-((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water pH=2.99 - 3.39; Inert atmosphere; Cooling with ice;	100%

betaine (107-43-7) + nicotinamide mononucleotide (1094-61-7) → 1-carboxy-N,N,N-trimethylmethanaminium ((2R,35,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; for 0.166667h;	97%

L-phenylalanine (63-91-2) + nicotinamide mononucleotide (1094-61-7) → (S)-1-carboxy-2-phenylethan-1-aminium-((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water pH=3.43 - 4; Cooling with ice;	96%

L-Cysteine (52-90-4) + nicotinamide mononucleotide (1094-61-7) → (R)-1-carboxy-2-mercaptoethan-1-aminium-((2R,3R,4S,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water pH=3.38 - 3.86; Cooling with ice;	95%

L-asparagine (70-47-3) + nicotinamide mononucleotide (1094-61-7) → (S)-3-amino-1-carboxy-3-oxopropan-1-aminium-((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water pH=3.38 - 3.86; Cooling with ice;	95%

nicotinamide mononucleotide (1094-61-7) + adenosine 5'-monophosphate (47287-36-5, 119923-66-9) + adenosine‐5'‐triphosphate disodium salt (606-67-7, 987-65-5, 4691-96-7, 15237-44-2, 20978-32-9, 71997-34-7, 71997-37-0, 71997-53-0, 71997-56-3) → nicotinamide adenine dinucleotide (76961-04-1)

Conditions	Yield
With 1,3-dimercaptopropanol; AdK on PAN gel; NAD pyrophosphorylase; PPiase; potassium acetate; magnesium chloride In water for 3h; Ambient temperature; pH: 7.0;	91%

L-methionine (63-68-3) + nicotinamide mononucleotide (1094-61-7) → (S)-1-carboxy-3-(methylthio)propan-1-aminium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; pH=Ca. 4.4 - 4.6;	89%

morpholin-4-yl-phosphonic acid mono-5′-[6-(pyrrol-2-yl)-9-β-D-ribofuranosyl-purine] + nicotinamide mononucleotide (1094-61-7) → P1-[6-(pyrrol-2-yl)-purine-9-β-D-ribofuranos-5'-yl]-P2-[nicotinamide-1-β-D-ribofuranos-5′-yl]pyrophosphate

Conditions	Yield
With magnesium sulfate; manganese(ll) chloride In formamide at 20℃; for 12h; Inert atmosphere;	87%

nicotinamide mononucleotide (1094-61-7) + glycine (56-40-6) → carboxymethanaminium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methvl phosphate

Conditions	Yield
In water pH=3.22 - 3.9; Inert atmosphere; Cooling with ice;	85%

L-serin (56-45-1) + nicotinamide mononucleotide (1094-61-7) → (S)-1-carboxy-2-hydroxyethan-1-aminium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water pH=3.22 - 3.8; Inert atmosphere; Cooling with ice;	83%

((2R,3R,4R,5R)-5-(4-aminothieno[3,4-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen triphosphate + nicotinamide mononucleotide (1094-61-7) → 1-((2R,3R,4R,5R)-5-((((((((2R,3R,4R,5R)-5-(4-aminothieno[3,4-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(hydroxy)phosphoryl)oxy)(hydroxy)phosphoryl)oxy)methyl)- 3,4-dihydroxytetrahydrofuran-2-yl)-3-carbamoylpyridin-1-ium

Conditions	Yield
With Saccharomyces cerevisiae inorganic pyrophosphatase; Homo sapiens recombinant nicotinamide mononucleotide adenylyl transferase 1; potassium chloride; sodium chloride; magnesium chloride In ethanol at 37℃; for 2.16667h; Enzymatic reaction;	81%

7-deaza-8-bromoadenosine 5'-monophosphate morpholidate triethylammonium salt + nicotinamide mononucleotide (1094-61-7) → 7-deaza-8-bromo nicotinamide adenine dinucleotide triethylammonium salt (213894-71-4)

Conditions	Yield
With magnesium sulfate; formamide; manganese(ll) chloride at 20℃; for 48h;	79%

L-alanin (56-41-7) + nicotinamide mononucleotide (1094-61-7) → C11H15N2O8P*C3H7NO2

Conditions	Yield
In water pH=3.22-3.8; Inert atmosphere; Cooling with ice;	79%

C14H23N6O10P (1278592-46-3) + nicotinamide mononucleotide (1094-61-7) → C25H36N8O17P2 (1278592-45-2)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; sodium hydroxide; magnesium chloride; N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid at 37℃;	67%

nicotinamide mononucleotide (1094-61-7) + L-carnitine (541-15-1) → (R)-3-carboxy-2-hydroxy-N,N,N-trimethylpropan-1-aminium ((2R,35,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate

Conditions	Yield
In water at 10℃; for 0.166667h;	67%

nicotinamide mononucleotide (1094-61-7) + acetic anhydride (108-24-7) → 2',3'-di-O-acetylnicotinamide mononucleotide (154591-45-4)

Conditions	Yield
With pyridine In water at 0℃; for 3h;	65%
With pyridine In water at 0℃; for 48h;
With pyridine at 0 - 5℃; for 24h; Inert atmosphere;
With pyridine In water at -5 - 0℃; for 24h; Inert atmosphere;

6-N-methyladnenosine 5'-monophosphate morpholidated triethylammonium salt + nicotinamide mononucleotide (1094-61-7) → 6-N-methyl nicotinamide adenine dinucleotide triethylammonium salt

Conditions	Yield
Stage #1: 6-N-methyladnenosine 5'-monophosphate morpholidated triethylammonium salt; nicotinamide mononucleotide With magnesium sulfate; manganese(ll) chloride In formamide at 20℃; for 48h; Inert atmosphere; Stage #2: With triethylamine carbonate In formamide; acetonitrile	64%

C26H36N7O9P (1352621-63-6) + nicotinamide mononucleotide (1094-61-7) → 8-(3-(Boc-aminomethyl)phenyl) NAD (1352621-54-5)

Conditions	Yield
With magnesium sulfate; manganese(ll) chloride In formamide at 20℃; for 24h; Inert atmosphere;	61%

Upstream product

• 23111-00-4 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) 
• 98-92-0 nicotinamide 
• 97-55-2 5-phosphoribosyl-1-pyrophosphate 
• 53-84-9 NAD 
• 53406-00-1 3-carbamoyl-1-(2,4-dinitrophenyl)pyridinium chloride 
• 87763-86-8 ribose 5-phosphate bis(cyclohexylammonium) salt 
• 14050-66-9 phosphoribosylamine 
• 78687-39-5 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium bromide 
• 18784-01-5 N¹-(2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl)-3-aminocarbonylpyridinium bromide 
• 78687-38-4 N¹-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-3-aminocarbonylpyridinium bromide 
• 47287-36-5 adenosine 5'-monophosphate 
• 6974-32-9 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose 
• 22860-91-9 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide 
• 105499-44-3 2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride 

Downstream Products

• 75501-82-5 4'-(3-2)>propylamino)acetophenon 
• 75501-83-6 4'-(6-2)>hexylamino)acetophenon 
• 98-92-0 nicotinamide 
• 193698-75-8 C₂₇H₄₂N₉O₁₇P₃ 
• 53-84-9 NAD 
• 66844-06-2 P1-(nicotinamine-ribos-5'-yl)-P2-(adenine-arabinofuranos-5'-yl)pyrophosphate 
• 75501-85-8 2,3',5'-Tribrom-4'-(3-2)>propylamino)acetophenon 
• 61-19-8 5'-adenosine monophosphate 
• 1018828-98-2 8-phenyl NAD 
• 1352621-54-5 8-(3-(Boc-aminomethyl)phenyl) NAD 
• 60902-13-8 3'dNAD+ 
• 1341-23-7 1-(β-D-ribofuranosyl)-nicotinamide 
• 53-57-6 NADPH 
• 53-84-9 nicotiamide adenine dinucleotide 

Relevant articles and documents

A fluorometric assay for high-throughput screening targeting nicotinamide phosphoribosyltransferase

Nicotinamide adenine dinucleotide (NAD) plays a crucial role in many cellular processes. As the rate-limiting enzyme of the predominant NAD biosynthesis pathway in mammals, nicotinamide phosphoribosyltransferase (Nampt) regulates the cellular NAD level. Tumor cells are more sensitive to the NAD levels, making them more susceptible to Nampt inhibition than their nontumorigenic counterparts. Experimental evidence has indicated that Nampt might have proangiogenic activity and supports the growth of some tumors, so Nampt inhibitors may be promising as antitumor agents. However, only four Nampt inhibitors have been reported, and no high-throughput screening (HTS) strategy for Nampt has been proposed to date, largely limiting the drug discovery targeting Nampt. Therefore, the development of a robust HTS strategy for Nampt is both imperative and significant. Here we developed a fluorometric method for a Nampt activity assay by measuring the fluorescence of nicotinamide mononucleotide (NMN) derivative resulting from the enzymatic product NMN through simple chemical reactions. Then we set up an HTS system after thorough optimizations of this method and validated that it is feasible and effective through a pilot screening on a small library. This HTS system should expedite the discovery of Nampt inhibitors as antitumor drug candidates.

A novel preparation of nicotinamide mononucleotide

Nicotinamide mononucleotide is conveniently prepared from nicotinamide adenine dinucleotide by specific hydrolysis of the pyrophosphate bond using the Zr4+ ion as catalyst.

Nicotinamide-Containing Di- and Trinucleotides as Chemical Tools for Studies of NAD-Capped RNAs

We report the chemical synthesis of a set of nicotinamide adenine dinucleotide (NAD) cap analogues containing chemical modifications that reduce their susceptibility to NAD-RNA-degrading enzymes. These analogues can be incorporated into transcripts in a similar way as NAD. Biochemical characterization of RNAs carrying these caps with DXO, NudC, and Nudt12 enzymes led to the identification of compounds that can be instrumental in unraveling so far unaddressed biological aspects of NAD-RNAs.

A chemical synthesis of nicotinamide adenine dinucleotide (NAD+)

A practical synthesis of nicotinamide mononucleotide (β-NMN) and a high yield coupling with AMP-morpholidate that also provides NAD+ in an efficient manner are reported.

Enzymatic and chemical syntheses of vacor analogs of nicotinamide riboside, nmn and nad

It has recently been demonstrated that the rat poison vacor interferes with mammalian NAD metabolism, because it acts as a nicotinamide analog and is converted by enzymes of the NAD salvage pathway. Thereby, vacor is transformed into the NAD analog vacor adenine dinucleotide (VAD), a molecule that causes cell toxicity. Therefore, vacor may potentially be exploited to kill cancer cells. In this study, we have developed efficient enzymatic and chemical procedures to produce vacor analogs of NAD and nicotinamide riboside (NR). VAD was readily generated by a base-exchange reaction, replacing the nicotinamide moiety of NAD by vacor, catalyzed by Aplysia californica ADP ribosyl cyclase. Additionally, we present the chemical synthesis of the nucleoside version of vacor, vacor riboside (VR). Similar to the physiological NAD precursor, NR, VR was converted to the corresponding mononucleotide (VMN) by nicotinamide riboside kinases (NRKs). This conversion is quantitative and very efficient. Consequently, phosphorylation of VR by NRKs represents a valuable alternative to produce the vacor analog of NMN, compared to its generation from vacor by nicotinamide phosphoribosyltransferase (NamPT).

Chemical synthesis method of NMN

The invention discloses a chemical synthesis method of NMN. The synthesis method comprises the following steps: firstly, enabling ribofuranose and niacinamide to react; then enabling a generated compound to react with metaphosphate; after reacting, acidifying; and then purifying to obtain the high-purity NMN. Compared with enzymatic reaction, the synthesis method disclosed by the invention has the advantages of low raw material cost, moderate and stable technological conditions and easiness for controlling; indexes of products of different batches are close and the reaction productivity is easy to improve; and compared with a fermentation method, the product obtained by the preparation method has high safety and the application prospect of the product is improved.

PRODUCTION OF NMN AND ITS DERIVATIVES VIA MICROBIAL PROCESSES

The present invention relates to microbial production of nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide adenine dinucleotide (NAD) using a genetically modified bacterium.

Method for preparing nicotinamide mononucleotide (NMN)

The present invention provides a method for preparing nicotinamide mononucleotide (NMN) by bioanalysis. The method includes a step of catalytically reacting a plurality of raw materials including nicotinamide, ATP, and ribose in the presence of nicotinamide phosphoribosyltransferase (Nampt), ribose phosphate pyrophosphokinase, and ribokinase, to prepare the NMN.

Preparation method of beta-nicotinamide mononucleotide

The invention discloses a preparation method of beta-nicotinamide mononucleotide. According to the method disclosed by the invention, the beta-nicotinamide mononucleotide is prepared by taking a compound shown as a formula II as a raw material and sequentially carrying out glycosylation condensation, deprotection, phosphorylation and acylation protection group removal reaction. Compared with methods in the prior art, the method provided by the invention has the advantages of high yield, simple operation, easy purification of intermediates, good phosphorylation selectivity and the like.

Chemical synthesis method of beta-nicotinamide mononucleotide

The invention provides a chemical synthesis method of beta-nicotinamide mononucleotide. The method comprises the following steps: taking 1, 2, 3, 5-tetrabenzoyloxy-2-C-methyl-beta-D-ribofuranose and nicotinamide as initial raw materials, and sequentially carrying out condensation reaction, benzoyl protecting group removal and phosphorylation reaction, so as to prepare the beta-nicotinamide mononucleotide. The high-purity beta-nicotinamide mononucleotide can be obtained through three steps of reaction (each step of reaction does not need purification) and one step of desalination purification. The method has the advantages of easily available raw materials, short reaction route, simple post-treatment, environmental protection and high total reaction yield, and is suitable for industrial production.