5950-12-9Relevant articles and documents
Mild, Metal-Free and Protection-Free Transamidation of N-Acyl-2-piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N-Acyl-2-piperidones
Subramani, Muthuraman,Rajendran, Saravana Kumar
, p. 3677 - 3686 (2019/06/08)
Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N-acyl-2-piperidones with a broad range of amines is demonstrated under exceedingly mild and metal-free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal-catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl-N-acyl-2-piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N-acyl-2-piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X-ray analysis of an N-acyl-2-piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N-acyl-2-piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.
Synthesis and biological evaluation of piperic acid amides as free radical scavengers and αglucosidase inhibitors
Takao, Koichi,Miyashiro, Takaki,Sugita, Yoshiaki
, p. 326 - 333 (2015/09/08)
A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 μM; 13: EC50 28 μM; 15: EC50 20 μM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 μM; 18: IC50 21 μM; 23: IC50 12 μM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 μM; 15: IC50 46 μM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel αglucosidase inhibitors with antioxidant activity.
Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors
Sangwan, Payare L.,Koul, Jawahir L.,Koul, Surrinder,Reddy, Mallepally V.,Thota, Niranjan,Khan, Inshad A.,Kumar, Ashwani,Kalia, Nitin P.,Qazi, Ghulam N.
experimental part, p. 9847 - 9857 (2009/04/11)
Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis, bioevaluation and structure related activity of these efflux pump inhibitors.
A simple synthesis of piperlonguminine
Seung, Ho Lee,Dong, Hyun Kim,Jeong, Ah Kim,Jahng, Yurngdong
, p. 407 - 410 (2007/10/03)
A simple and practical method for the synthesis of an alkaloid piperlongumine, an efficient inhibitor of α-melanocyte stimulating hormone, was established by employing Wadsworth-Horner modified Wittig reaction as a key step.
Stereoselective synthesis of naturally occurring unsaturated amide alkaloids by a modified Ramberg-Baecklund reaction
Li, Yang,Zhang, Yu,Huang, Zhi,Cao, Xiaoping,Gao, Kun
, p. 622 - 630 (2007/10/03)
A convenient and rapid approach for the synthesis of naturally occurring unsaturated amide alkaloids 1a-1n by the recently developed one-flask Ramberg-Baecklund reaction is described. The starting material was alcohol 3, which was transformed into thiolacetate 4 using the Mitsunobu reaction. In situ cleavage of acetyl moiety of 4, followed by alkylation of the resulting thiol with appropriate chloroacetamide 5, provided the sulfide 6. Oxidation of sulfide 6 gave the corresponding sulfone 2. Treatment of the sulfone 2 with the dibromodifluoromethane in the presence of alumina-supported potassium hydroxide in dichloromethane solution afforded unsaturated amide alkaloids 1a-1n. To the best of our knowledge, the synthesis of 1e and 1i was reported for the first time.
Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation
Venkatasamy, Radhakrishnan,Faas, Laura,Young, Antony R.,Raman, Amala,Hider, Robert C.
, p. 1905 - 1920 (2007/10/03)
A wide range of piperine analogues has been synthesised in order to undertake a structure-activity study of their ability to stimulate melanocyte proliferation. Results demonstrate that an aromatic ring containing at least one ether function and a carbonyl group containing side chain is essential for this activity. A number of highly active piperine analogues have been identified, for instance 1-(3,4-methylenedioxyphenyl)-penta-2E,4E-dienoic acid methyl ester (5a), 1-E,E-piperinoyl-isobutylamine (4f) and 1-(3,4- methylenedioxyphenyl)-pentanoic acid cyclohexyl amide (20). A selection of analogues has also been evaluated for their effect on melanocyte morphology and melanogenesis. The piperine analogues altered cell morphology by increasing dendrite formation leading to bi-, tri- and quadripolar cells. These same analogues were found to increase total melanin in cell cultures, although melanin content per cell was not significantly altered from control in the presence of these compounds.
Catalytic Hunsdiecker reaction and one-pot catalytic Hunsdiecker-Heck strategy: Synthesis of α,β-unsaturated aromatic halides, α- (dihalomethyl)benzenemethanols, 5-aryl-2,4-pentadienoic acids, dienoates and dienamides
Naskar, Dinabandhu,Roy, Sujit
, p. 1369 - 1377 (2007/10/03)
The reaction of α,β-unsaturated aromatic (or heteroaromatic) carboxylic acids with N-halosuccinimides (1 equiv.) and catalytic tetrabutylammonium trifluoroacetate (0.2 equiv.) in dichloroethane results in facile halodecarboxylation affording the corresponding (E)-halides in good to excellent yields. A similar reaction, but with 2 equiv. of N-halosuccinimides in acetonitrile-water (1:1 v/v) results in the exclusive formation of the corresponding α-(dihalomethyl)benzenemethanols. Furthermore, a one-pot strategy has been developed combining catalytic Hunsdiecker reaction (using tetrabutylammonium trifluoroacetate in dichloroethane) and Heck coupling (using palladium acetate/triethylamine/triphenylantimony/dichloroethane) for the synthesis of 5-aryl-2,4-pentadienoic acids, esters and amides in moderate to good yields. The natural product piperine and pipergualamine has been synthesized via the above route. Mechanistic and theoretical studies (via AM1 calculations) provide a useful insight into the mechanism of the present halodecarboxylation reaction, suggesting an ionic pathway involving the attack of the halogenium ion across the carbon-carbon double bond, triggering the elimination of carbon dioxide. (C) 2000 Elsevier Science Ltd.
Synthesis and insecticidal activity of new amide derivatives of piperine
De Paula, Vanderlucia F.,De A Barbosa, Luiz C.,Demuner, Antonio J.,Pilo-Veloso, Dorila,Picanco, Marcelo C.
, p. 168 - 174 (2007/10/03)
The natural lipophilic amides piperine and piperiline were isolated from Piper nigrum L (Piperaceae). Piperine was hydrolysed into piperic acid (85% yield) which was converted into 16 amides (28-89% yield). The contact toxicity of all synthetic amides, and also that of piperine and piperiline, at the dose 10 μg per insect, was evaluated for the Brazilian economically important insects Ascia monuste orseis Latr, Acanthoscelides obtectus Say, Brevicoryne brassicae L, Protopolybia exigua DeSaus and Cornitermes cumulans Kollar. The results demonstrated that the insects have different sensivities to the various amides, with mortality ranging from 0 to 97.5% according to the compound and insect species. (C) 2000 Society of Chemical Industry.
Addition of carbon nucleophiles to aldehyde tosylhydrazones of aromatic and heteroaromatic-compounds: Total synthesis of piperine and its analogs
Chandrasekhar,Venkat Reddy,Srinivasa Reddy,Ramarao
, p. 2667 - 2670 (2007/10/03)
Addition of carbon nucleophiles to aldehyde tosylhydrazones of aromatic and heteroaromatic compounds is reported. New observations have been made wherein alkylative reduction is observed in some cases whereas alkylative fragmentation is noticed in others. These findings are exploited in the synthesis of the useful alkaloid piperine and its analogs. (C) 2000 Elsevier Science Ltd.
Infrared Spectra of Conjugated Amides: Reassignment of the C=O and C=C Absorptions
Nakamura, Norio,Kiuchi, Fumiyuki,Tsuda, Yoshisuke
, p. 2647 - 2651 (2007/10/02)
Inspections of the infrared spectra of more than twenty tertiary and secondary amides and acid-induced shift experiments clarified that, in open chain amides, the carbonyl absorption shifts to lower frequency by 10-20 cm-1 when a conjugation is introduced and that, among the plural absorptions at 1600-1700 cm-1 in conjugated amides, the lowest absorption (usually the most intense one) should be attributable to the C=O and the higher absorptions are assignable to the C=C.Keywords - conjugated amide; piperamide; IR; carbonyl absorption; acid-induced shift.
