Nonivamide

Nonivamide is a agonist, which exhibits 4d-EC50 value of 5.1 mg/L in static toxicity tests.

Solid|White powder or crystals; odourless

Nonivamide is a capsaicinoid that is the carboxamide resulting from the formal condensation of the amino group of 4-hydroxy-3-methoxybenzylamine with the carboxy group of nonanoic acid. It is the active ingredient in many pepper sprays. It has a role as a lachrymator. It is a capsaicinoid and a member of phenols.|Nonivamide is found in herbs and spices. It is an alkaloid from the Capsicum species. The structures of [DB06774] and nonivamide differ only slightly with respect to the fatty acid moiety of the side chain (8-methyl nonenoic acid versus nonanoic acid). Nonivamide is a flavoring ingredient. Nonivamide is an organic compound and a capsaicinoid. It is an amide of pelargonic acid and vanillylamine. It is naturally found in chili peppers but manufactured to produce a synthetic form for various pharmacologic preparations. This drug has been studied in combination with Nicarboxil in the treatment of lower back pain. Nonivamide has also been studied for its anti-inflammatory properties, as well as in fat loss therapies and has demonstrated promising results,,,.

To a solution of the hydrochloride or hydrobromide salt of an amine (1 mmol) in anhydrous N, N- dimethylformamide (DMF) (2 mL) was added N, N- diisopropylethylamine (DIPEA) (2 mmol) to liberate the amine. After stirring at room temperature for 10 min, nonanoyl chloride (1 mmol) was added. The solution was stirred at room temperature for 6 to 24 h. After the reaction, water (40 mL) was added to the solution. The reaction mixture was transferred to a separating funnel and extracted with dichloromethane, CHIn a three-neck 500 mL flask, 30.0 g (0.196 mol) of vanillin was added.31.0 g (0.196 mol) of n-decanoic acid and 300 mL of toluene were added.Boric acid 0.6g (9.8mmol), a three-neck flask fitted with a thermometer, A mouth water separator + reflux condenser (the water separator is loaded into the reaction flask, Then install the reflux condenser above the water separator.)Another mouth is closed, stirring is started, and the temperature is raised to 130°C for 8 hours.After the reaction is completed, it is cooled to room temperature.Add 50mL of water twice to wash (extract boric acid), After drying over anhydrous sodium sulfate, Recovery of toluene under reduced pressure at 60 °C using a rotary evaporatorTo the distillation of toluene is 2/3 of the original volume, stop decompression recovery, The remaining liquid is transferred to the cryogenic reactor, Stir and crystallize at -20°C for 3h, filter, The resulting crystals are washed with toluene.Drained to give 50.3 g of a white powdery solid with a yield of 87.4percent.HPLC purity 99.1percent.White powder solids analysis:A microwave-vial containing a solution of 1 (0.2 mmol, 1.0 equiv.), ammonium formiate (37.8 mg, 0.6 mmol, 3.0 equiv.) and Pd°-catalyst(Pd°-AmP-MFC, 13.4 mg, 0.01 mmol, 8 wtpercent, 5 molpercent) or(Pd°-CPG, 569A, 74.0 mg, 0.013 mmol, 6.6 molpercent) in toluene (1 mL) under ISfc conditions was stirred at 80The dried crude reaction mixture from the previous step (containing vanillylamine 94 mg, 0.62 mmol, 1.00 equiv.) was dissolved in 2-methyl-2-butanol (31 mL, 20 mM). To the reaction was added Ms 4A (2 g), compound 5b (98.7 mg, 0.62 mmol, 1.00 equiv.) and lipase (1.9 g, 20 mg/niL). The reaction was stirred at 45°C for 48 h. Afterwards the reaction was cooled to room temperature and filtered. The solvent was removed under reduced pressure and the crude material was purified by chromatography to afford nonivamide (7b) (isolated yield 52 percent) as light yellow oil.1) Preparation of crude product mixture: 105 g of vanillinamine hydrochloride was added to a mixture consisting of 200 g of sodium hydrogencarbonate, 500 mL of dichloromethane and 600 mL of water, and the mixture was stirred well and the mixture was further heated at room temperature (Methylene chloride: volume: 146.4 mL) was added dropwise over 1 hour. After completion of the dropwise addition, the temperature was raised to 42 ° C and maintained at that temperature for 1.5 hours. To obtain a crude product mixture (1420 mL);(2) Crystallization purification: The crude product mixture was cooled to room temperature, first using 200 mL of 25percentHydrochloric acid solution was shaken and allowed to stand for separation. The organic phase was separated (about 750 mL), and 150 mL of a 20percentOf the sodium hydroxide solution was shaken and the organic phase was washed and allowed to stand for separation. The organic phase was separated again750 mL), washed with 200 mL of water, and partitioned. After washing with water, the organic phase (about 750 mL)150 mL of methylene chloride was distilled off to give a concentrated organic phase (ca. 600 mL), which was added to the concentrated organic phase1080mL petroleum ether after cooling crystallization, cooling rate of 0.25 / min, crystallization termination temperature of aboutAt -10 & lt; 0 & gt; C, maintaining the crystallization termination temperature for at least 30 min, filtering at the crystallization termination temperature, Dried to obtain solid synthetic capsaicin 148.6g, the yield was 91.5percent, by high performance liquid chromatography(HPLC) to determine the purity of 99.5percent.Into a reactor equipped with a heating, stirring, and a thermometer, 112 g of vanillin amine hydrochloride obtained above was added to 670 ml of a DMF solvent, and the mixture was stirred at room temperature until the solid was completely dissolved and 95.2 g Nonanoic acid was added thereto.The was cooled to 0°C with an ice bath, 134.4g of triethylamine was added, the temperature was stabilized at 0-5°C, and 235.2g of a condensing agent HBTU was added under stirring. The reaction was naturally warmed to room temperature and stirred overnight. After the reaction was completely detected by TLC, Add 1100 ml of ethyl acetate and 330 ml of water to the reaction mixture. Stir well and place in liquid in a separatory funnel. Discard the aqueous layer and obtain ethyl acetate layers of 5 wtpercent sodium bicarbonate solution, 2 wtpercent hydrochloric acid, respectively. The saturated brine was washed three times each, 1200 ml/time, and then 100 g of anhydrous sodium sulfate was added to the ethyl acetate layer for drying for 3 hours. The sodium sulfate was removed by filtration, and the filtrate was placed in a reactor and heated to 45° C. with stirring and reduced. About 820 ml of ethyl acetate was distilled off and cooled to room temperature. 540 ml of petroleum ether was added to crystallize for 3 hours and filtered. The solid was dried at 40-45° C. for 10 hours to obtain 156.4 g of Nonivamide as the target product. The total yield was 81.1percent. The obtained capsaicin was analyzed by HPLC and its purity was 98.8percent.

1. Analgesic (topical), depletes Substance P
2. N-Vanillylnonanamide is a synthetic analogue of Capsaicin (175680) with similar bioactivity.

Molecular Weight:293.4
XLogP3:4.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:10
Exact Mass:293.19909372
Monoisotopic Mass:293.19909372
Topological Polar Surface Area:58.6
Heavy Atom Count:21
Complexity:283
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes