74058-71-2

Usage

Uses

Used in Pharmaceutical Industry:
Hexadecanamide, N-(phenylmethyl)is used as a potential inhibitor for the human enzyme fatty acid amide hydrolase (FAAH) for its ability to modulate the activity of this enzyme, which plays a crucial role in various physiological processes. By inhibiting FAAH, it may contribute to the development of new therapeutic approaches for treating conditions related to the dysregulation of the endocannabinoid system.

Biological Activity

n-benzylpalmitamide is an inhibitor of fatty acid amide hydrolase (faah) [1].the fatty acid amide hydrolase (faah) is a mammalian integral membrane enzyme responsible for the hydrolysis of anandamide, an endocannabinoid. the faah is involved in degrading the fatty acid amide family of endogenous signaling lipids, including the endogenous cannabinoid anandamide and the sleep-inducing substance oleamide. faah belongs to is a member of amidase signature (as) family. the faah integrates into cell membranes and terminates fatty acid amide signaling in vivo [2]. genetic mutations in faah may constitute important risk factors for problem drug use and support a potential link between functional abnormalities in the endogenous cannabinoid system and drug abuse and dependence [3].n-benzylpalmitamide was a long-chain fatty acid amide isolated from the maca (l. meyenii) plant and was structurally related to cannabinoids. n-benzylpalmitamide was a moderate inhibitor of faah and inhibited 44% activity of faah at 500 μm [1].

references

[1] wu h, kelley c j, pino-figueroa a, et al. macamides and their synthetic analogs: evaluation of in vitro faah inhibition[j]. bioorganic & medicinal chemistry, 2013, 21(17): 5188-5197.[2] deutsch d g, ueda n, yamamoto s. the fatty acid amide hydrolase (faah)[j]. prostaglandins, leukotrienes and essential fatty acids (plefa), 2002, 66(2): 201-210.[3] sipe j c, chiang k, gerber a l, et al. a missense mutation in human fatty acid amide hydrolase associated with problem drug use[j]. proceedings of the national academy of sciences, 2002, 99(12): 8394-8399.

Synthetic route

C28H40N2O2 (100663-86-3) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2) + (E)-2-pyridylphenyl ketoxime (14178-31-5)

Conditions	Yield
In dichloromethane for 24h; Ambient temperature;	A 99% B 100%

1-(2-Thioxo-thiazolidin-3-yl)-hexadecan-1-one (74058-64-3)

Conditions	Yield
In dichloromethane for 0.0333333h; Ambient temperature;	96%

+ benzylamine → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
at 50 - 60℃; for 16h;	94%

1-hexadecylcarboxylic acid (57-10-3) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
With mesoporous silica MCM-41 In toluene for 12h; Reflux;	92%
Stage #1: 1-hexadecylcarboxylic acid With Bromotrichloromethane; triphenylphosphine In dichloromethane for 0.75h; Reflux; Stage #2: benzylamine In dichloromethane for 14h; Reflux;	89%
Stage #1: 1-hexadecylcarboxylic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: benzylamine With dmap In dichloromethane at 20℃; for 18h;	86%

hexadecanoic acid ethyl ester (628-97-7) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
With indium (III) iodide at 110 - 120℃; for 8.5h;	91%
at 150℃;

n-tetradecanoic acid (544-63-8) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Stage #1: n-tetradecanoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: benzylamine With dmap In dichloromethane at 20℃; for 18h;	89%

diphenylmethylsilanecarboxylic acid (18414-58-9) + pentadecylzinc(II) bromide + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions

Yield

Stage #1: pentadecylzinc(II) bromide With (2-morpholino-N-(quinolin-8-yl)acetamido)nickel(II) chloride In tetrahydrofuran; N,N-dimethyl acetamide at 20℃; for 0.5h; Inert atmosphere; Glovebox; Stage #2: diphenylmethylsilanecarboxylic acid; benzylamine With potassium fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; Sealed tube; Glovebox;

46%

benzylamine (100-46-9) + n-hexadecanoyl chloride (112-67-4) → hexadecanoic acid benzylamide (74058-71-2)

1-hexadecylcarboxylic acid (57-10-3) + thorium oxide → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: DCC-DMAP 2: 99 percent / CH2Cl2 / 24 h / Ambient temperature View Scheme

n-hexadecanoyl chloride (112-67-4) + ent-17-methyl-morphinan-3-ol → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N 2: 99 percent / CH2Cl2 / 24 h / Ambient temperature View Scheme

1-hexadecylcarboxylic acid (57-10-3) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: dicyclohexylcarbodiimide 2: 96 percent / CH2Cl2 / 0.03 h / Ambient temperature View Scheme

pentadecyl bromide (629-72-1) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: iodine / N,N-dimethyl acetamide / 20 °C / Inert atmosphere; Glovebox 1.2: 70 °C / Inert atmosphere; Glovebox 2.1: (2-morpholino-N-(quinolin-8-yl)acetamido)nickel(II) chloride / tetrahydrofuran; N,N-dimethyl acetamide / 0.5 h / 20 °C / Inert atmosphere; Glovebox 2.2: 2 h / 20 °C / Inert atmosphere; Sealed tube; Glovebox View Scheme

Upstream product

• 74058-64-3 1-(2-Thioxo-thiazolidin-3-yl)-hexadecan-1-one 
• 100-46-9 benzylamine 
• 18414-58-9 diphenylmethylsilanecarboxylic acid 
• 629-72-1 pentadecyl bromide 
• 544-63-8 n-tetradecanoic acid 
• 57-10-3 1-hexadecylcarboxylic acid 
• 555-44-2 glyceroltripalmitate 
• 100663-86-3 C₂₈H₄₀N₂O₂ 
• 112-67-4 n-hexadecanoyl chloride 
• 628-97-7 hexadecanoic acid ethyl ester 

Relevant academic research and scientific papers

Synthesis and biological screening of a library of macamides as TNF-α inhibitors

Thirty-five macamide analogues were synthesised by modifying the initial molecular structure. The resulting structures were confirmed using NMR and MS. Cytotoxicity and the anti-inflammatory activity of these synthetic macamides were evaluated in the THP-1 cell line. Preliminary biological evaluation indicated that most of these synthetic macamides did not present cytotoxicity (MTT assay) in the tested cell line with respect to the control (actinomycin D). Regarding the anti-inflammatory activity, several analogues had a greater potential for inhibition of TNF-α than natural macamides. Synthetic macamide 4a was the most active (IC50 = 0.009 ± 0.001 μM) compared to the C87 (control). Through looking at the link between the chemical structure and the activity, our study proves that changes made to natural macamides at the level of the alkyl chain, the benzyl position, the amide bond, and the addition of two methyl groups to the aromatic ring (meta position) lead us to obtaining new macamides with greater anti-inflammatory activity. This journal is

Synthesis of Aliphatic Carboxamides Mediated by Nickel NN2-Pincer Complexes and Adaptation to Carbon-Isotope Labeling

The development of a nickel-mediated aminocarbonylation utilizing NN2-pincer Ni-complexes, alkylzinc reagents, stoichiometric carbon monoxide and amines is described for the first time, which can be adapted to late-stage carbon-isotope labeling. This work expands the scope of the highly established palladium-promoted version of the reaction, by allowing carbon-sp3 fragments to take part in the three-component reaction. Finally, the results obtained show a remarkable effect of the pincer ligand for the reductive elimination step with the amine, which is followed by 13C NMR spectroscopy studies.

Maca amide synthesis method and use thereof

The invention relates to a synthetic method of MACAmide. The method includes following steps: with a fatty acid and benzylamine or m-methoxybenzylamine as reaction raw materials, mixing the raw materials in a dichloromethane solution in which HOAt, EDC.HCl and DIPEA are dissolved; performing a reaction with stirring; washing a reaction product with water; and drying a substance being undissolved in water to obtain the MACAmide. The method is simple in processes and the raw materials are easy to obtain. Operation conditions of the method are easy to control. The reaction product can reach a purity of 95% without purification. The invention provides basis for industrialized synthesis of the MACAmide. In addition, the MACAmide has effects of enhancing male reproductive ability and treating male sexual dysfunction. The invention provides market prospects to application of the MACAmide.

The use of BrCCl3-PPh3 in Appel type transformations to esters, O-acyloximes, amides, and acid anhydrides

Esters, acyloximes, amides and acid anhydrides have been prepared from the respective carboxylic acids, oximes, amines and alcohols by the use of the reagent combination BrCCl3-PPh3. The reactions obviate the handling acyl halides or more aggressive reagents PCl3, POCl3, or SOCl2. Furthermore, the environmentally hazardous CCl4 used in Appel-type reactions is replaced with BrCCl3, a reagent of less environmental concern.

Antiproliferative activity of synthetic fatty acid amides from renewable resources

In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line - the most aggressive CNS cancer.

Macamides and their synthetic analogs: Evaluation of in vitro FAAH inhibition

Maca (Lepidium meyenii), a traditional food crop of the Peruvian Andes is now widely touted as a dietary supplement. Among the various chemical constituents isolated from the plant are a unique series of non-polar, long-chain fatty acid N-benzylamides known as macamides. We have synthesized 11 of the 19 reported macamides and have tested each as potential inhibitors of the human enzyme, fatty acid amide hydrolase (FAAH). The five most potent macamides were FAAH inhibitors (IC50 = 10-17 μM). These amides were derivatives of oleic, linoleic and linolenic acids and benzylamine or 3-methoxybenzylamine. Of the three compounds evaluated in a pre-incubation time study, two macamides were not irreversible inhibitors of FAAH. The third, a carbamate structurally related to macamides, was shown to be an irreversible inhibitor of FAAH (IC50 = 0.153 μM).

Mesoporous silica MCM-41 as a highly active, recoverable and reusable catalyst for direct amidation of fatty acids and long-chain amines

Direct amidation of fatty acids with long-chain amines was successfully performed by mesoporous silica MCM-41, which showed the highest catalytic activity among other used homo- and heterogeneous catalysts. It was found that MCM-41 can be easily recovered from the reaction mixture followed by simple calcination treatment and reused without loss of its catalytic activity. The Royal Society of Chemistry.

Synthesis and antituberculosis activity of new fatty acid amides

This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 μg/mL for resistance strains.

A simple and convenient procedure for the conversion of esters to secondary amides

An improved procedure has been developed for the direct conversion of carboxylic esters to secondary amides by simple treatment with primary amines in presence of indium triiodide.

A Novel Technique for the Preparation of Secondary Fatty Amides. III. Alkanolamides, Diamides and Aralkylamides

A low-temperature synthesis of fatty alkanolamides, fatty diamides and fatty aralkylamides directly from triglycerides and primary amines provides essentially quantitative yields of the various products.The reactions run to completion in 3-12 h at temperatures of 50-60 deg C, approximately 100 deg C lower than employed in present conventional practice.The amines are used in excess and serve as solvent, reagent and, perhaps, as catalyst.The amides were characterized by melting point and spectroscopic (infrared and nuclear magnetic resonance) methods.If the mixed amides produced from the various natural triglyceride mixtures of fats and oils are acceptable products, this synthetic method provides these products in satisfactory quality while conserving energy and avoiding the intermediate production of free fatty acids or their esters. KEY WORDS: Alkanolamides, amidation, aralkylamides, diamides, methyl tallowate, palmitic acid, tallow, tripalmitin.