Study on Antitumor Activity of Piperidine Derivatives

[Objectives]This study was conducted to investigate the effects of piperidine derivatives on the proliferation and apoptosis of tumor cells(Hele).[Methods]The target end product(piperidine derivative)was synthesized through a series of organic reactions.The MTT assay was adopted to detect the effect of piperidine derivative on the proliferation activity of Hele cells.The ROS fluorescence probe method was used to detect the changes of reactive oxygen species.The JC-1 method was applied to detect the changes of MMP in Hele cells.Flow cytometry was adopted to detect the apoptosis of Hele cells.[Results]The cell survival rates were 70.84%,65.46%and 54.48%when the drug concentration was 100,110 and 120μmol/L,respectively.When the drug concentration increased to 120μmol/L,the cell survival rate decreased by nearly half.The fluorescence intensity of active oxygen in the control group was 1,and when the drug concentrations were 100,110 and 120μmol/L,the fluorescence intensity of active oxygen was,respectively,1.315,1.478 and 1.677,which were higher than that in the control group.The red/green fluorescence intensity of the MMP control group was 1.819,and that of drug groups was,respectively,1.643,1.164 and 0.665,which were lower than that of the control group.The apoptosis rates were 10.79%,22.91%and 38.54%at the drug concentrations of 100,110 and 120μmol/L,respectively,showing a concentration dependent effect.The results showed that the piperidine derivative could inhibit the proliferation of Hele cells and induce apoptosis,which was positively correlated with the concentration.[Conclusions]This study provides theoretical basis and reference for the anti-tumor research of piperidine.

Synthesis of FER zeolite with piperidine as structure-directing agent and its catalytic application

The synthesis of ferrierite(FER)zeolite using piperidine as an organic structure‐directing agent was investigated.X‐ray diffraction,X‐ray fluorescence,N2‐adsorption,and scanning electron microscopy were used to characterize the crystal phases,textural properties,and particle morphologies of the zeolite samples.The crystallization behavior of the FER zeolite was found to be directly related to crystallization temperature.At150?C,pure FER phase was observed throughout crystallization.At160–170?C,MWW phase appeared first and gradually transformed into FER phase over time,indicating that the FER phase was thermodynamically favored.In the piperidine‐Na2O‐H2O synthetic system,alkalinity proved to be the crucial factor determining the size and textural properties of FER zeolite.Furthermore,the obtained FER samples exhibited good catalytic performance in the skeletal isomerization of1‐butene.

Syntheses and Characterizations of Two New Organic-inorganic Hybrids Based on Heteropolymolybdates and Piperidine Molecules

Two new organic-inorganic compounds [（CH2）5NH2]3[PMo12O40]·3[（CH2）NH] 1 and [（CH2）5NH2]6[P2Mo18O62]·5H2O 2 have been synthesized using conventional and hydrothermal methods, respectively, and characterized by elemental analyses, IR, TG and single-crystal X-ray diffraction. X-ray analyses show that in these compounds heteropolymolybdates [PMo12O40]^3- and [P2Mo18O62]^6- are reserved their Keggin or Dawson structures and linked to piperidine through electrostatic and hydrogen-bonding interactions.

COPOLYMERIZATION OF PROPYLENE WITH HINDERED PIPERIDINE MONOMER OVER A HIGH ACTIVITY SUPPORTED ZIEGLER-NATTA CATALYST

Copolymerization of propylene and hindered piperidine monomers was carried out over a high activity supported Ziegler-Natta catalyst, using Al(C2H5)(3) as cocatalyst. Factors which affect the copolymerization were studied, The copolymers exhibited high light stability without adding extra light stabilizers. A self-stabilized polypropylene was prepared.

Design,synthesis and biological estimation of 1-(benzoxazole-2-yl)piperazine and 4-(benzoxazole-2-yl)piperidine derivatives as potentialα_1-AR antagonists

Two series of 1-（benzoxazole-2-yl）piperazine （Sa-i） and 4-（benzoxazole-2-yl）piperidine compounds （10a-i） were designed, synthesized and evaluated for their α1-AR antagonistic activities. Biological assay in vitro indicated that 10h showed slightly stronger α1-AR antagonistic activity to that of our lead compound 1.

New Crystal Structure of Molecular Complex 1-Piperidine Carboxylate-Piperidinium-H_2O Studied by X-Ray Single Crystal Diffraction

Piperidine absorbs CO2 and H2O in air to form a molecular complex： piperidium-l-piperidinecarboxylate-H2O. The structure of the complex was characterized by X-ray single crystal diffraction. The crystal structure was determined to be triclinic, space group P1^-with a=0.648 6（8） nm, b=0.809 200） nm, c= 1.357 1（16） nm, a=96.96706）°, β =102.506（15）°,γ=104.202 05）°, Z=2. The complex is stabilized via five hydrogen bonds between the three components, N-O electrostatic interaction and O-O interaction （electron transfer） betweenl-piperidinecarboxylate and H2O. Due to electron transference of carbamate ion, the oxygen atom in water molecule is strongly negatively charged and the O-H bond is considerably shorter than that of the free molecule of water. The formation of the molecular complex is a reversible process and will decompose upon heating. The mechanism of formation and stabilization is further investigated herein.

Study of the distribution profile of piperidine alkaloids in various parts of Prosopis juliflora by the application of Direct Analysis in Real Time Mass Spectrometry(DART-MS)

Direct Analysis in Real Time Mass Spectrometry(DART-MS)was applied to identify and study the distribution profile of piperidine alkaloids in different parts of Prosopis juliflora,without isolation and separation of the compounds by standard chromatographic techniques.With the help of DART-MS,chemical fingerprint of raw plant parts were generated,which revealed the presence of piperidine alkaloids in leaf,pod and flower.A comparative study of the distribution pattern,showed variation in the presence and distribution of these alkaloids in various parts of P.juliflora.The leaves and pod displayed the largest alkaloid pattern with a total of 12 different alkaloids in each part,whereas only 4 alkaloids were present in flower.Alkaloids:julifloridine,prosopine,prosopinine and prosafrinine were ubiquitously distributed in all the alkaloid rich plant parts.Juliprosopine was pre-eminet alkaloid in leaf,whereas pod and flower displayed copious amounts of julifloridine.

Synthesis,Crystal Structure and Bioactivity of N-Phenethyl-4-hydroxy-4-phenyl Piperidine Hydrochloride

A novel compound N-phenethyl-4-hydroxy-4-phenyl piperidine hydrochloride （C19H24ClNO·H2O） has been synthesized and structurally characterized by elemental analysis, IR, ^1H NMR spectra and single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space group P212121 with a = 8.6306（8）, b = 11.0464（10）, c = 19.3221（18）A^°, V = 1842.1（3）A^°^3, Z = 4, Dc =1.211 g/cm^3,μ = 0.217 mm^-1, Mr= 335.86, F（000） = 720, S = 0.973, R = 0.0420 and wR = 0.1009 for 3627 unique reflections with 3157 observed ones （I 〉 2σ（I））. In the crystal, the dihedral angles made by piperidine ring with two benzene rings are 84.8（6） and 62.5（7）°, respectively. Intermolecular O-H…O and O-H…Cl hydrogen bonds involving water molecules form chains along the b axis, which stabilizes the crystal structure. The preliminary bioactivity tests indicated that the title compound has good effect of cellular growth inhibition to K562 cells and potential bioactivity of anti-leukemia.

NMR and FT-IR Analysis of New Molecular Complex 1-Piperidine-carboxylate-Piperidinium-H_2O

Piperidine absorbs CO2 and H2O contents in air to form a molecular complex： piperidium-1-piperidinecarboxylate-H2O. The structure of the complex was characterized by FT-IR and NMR. The complex is stabilized via five hydrogen bonds between the three components, N…O electrostatic interaction and O…O interaction （electron transfer） betweenl-piperidinecarboxylate and H2O. Through electron transfer from the carbamate ion, the oxygen atom in water molecule is strongly negatively charged and the O-H bond is considerably shorter than that of free water molecule. The formation of the molecular complex is a reversible process and will decompose upon heating. The mechanism of formation and stabilization is further investigated herein.

Organic-inorganic Hybrid Materials Based on Piperidine Derivatives and Semi-conductive Metal Iodine

Reactions of piperidine derivatives 4-(aminomethyl)piperidine(4-AMPD) and 1-methylpiperidin-4-amine(1-MPDA) with semi-conductive metal iodine SbI3 and PbI2 in concentrated HI aqueous solution afforded two one-dimensional(1 D) chain compounds [(4-AMPD)SbI5]n(1), [(1-MPDA)SbI5]n(2) and a two-dimensional(2 D) single layered organicinorganic hybrid material [(1-MPDA)PbI4]n(3), which were confirmed by X-ray single-crystal diffraction, infrared(IR) spectroscopy and powder X-ray diffraction(PXRD). Simultaneously, compounds 1~3 exhibit strong emission peaks at 600 nm for 1 and 2 and 570 nm for 3, which were originated from their inorganic moieties.

SYNTHESIS AND LIGHTFASTNESS PROPERTIES OF DYES CONTAINING HINDERED PIPERIDINE RESIDUES AS INTERNAL STABILIZING GROUPS

The representative azo and anthraquinone dyes containing an insulated hindered piperidinegroup were synthesized.The effect of these pendent groups on lightfastness properties of the dyeswas studied,both in ethyl acetate solution and on cellulose acetate and polyester films.The differ-ent trend of fading rates of azo dyes and anthraquinone dyes in solution and on substrates suggestsdifferent fading mechanisms operating in each case.

Mechanistic Study on the Monofunctional Binding of Hydrolysis Products of Non-planar Heterocyclic Complexes Trans-[PtCl_2NH_3(piperidine)] and Trans-[PtCl_2(piperidine)_2] to DNA Purine Bases

The monofunctional substitution reactions between trans-[PtCl（H2O）（NH3）（pip）]＋,trans-[Pt（H2O）2（NH3）（pip）]2＋,trans-[PtCl（H2O）（pip）2]＋,trans-[Pt（H2O）2（pip）2]2＋ （pip = piperidine） and adenine/guanine nucleotides are explored by using B3LYP hybrid functional and IEF-PCM salvation models. For the trans-[Pt（H2O）2（NH3）（pip）]2＋ and trans-[PtCl（H2O）（NH3）（pip）]＋ complexes,the computed barrier heights in aqueous solution are 13.5/13.5 and 11.6/11.6 kcal/mol from trans-Pt-chloroaqua complex to trans/cis-monoadduct for adenine and guanine,and the corresponding values are 20.7/20.7 and 18.8/18.8 kcal/mol from trans-Pt-diaqua complex to trans/cis-monoadduct for adenine and guanine,respectively. For trans-[PtCl（H2O）（pip）2]＋ and trans-[Pt（H2O）2（pip）2]2＋,the corresponding values are 21.5/21.3 and 19.4/19.4 kcal/mol,and 26.0/26.0 and 20.7/20.8 kal/mol for adenine and guanine,respectively. Our calculations demonstrate that the barrier heights of chloroaqua are lower than the corresponding values of diaqua for adenine and guanine. In addition,the free energies of activation for guanine in aqueous solution are all smaller than that for adenine,which predicts a preference of 1.9 kcal/mol when trans-[PtCl（H2O）（NH3）（pip）]＋ and trans-[Pt（H2O）2（NH3）（pip）]2＋ are the active agents and ～1.9 and ～ 5.3 kcal/mol when trans-[PtCl（H2O）（pip）2]＋ and trans-[Pt（H2O）2（pip）2]2＋ are the active agents,respectively. For the reaction of trans-Pt-chloroaqua （or diaqua） to cis-monoadduct,we obtain the same transition-state structure as from the reaction of trans-Pt-chloroaqua （or diaqua） to trans-monoadduct,which seems that the trans-Pt-chloroaqua （or diaqua） complex can generate trans-or cis-monoadduct via the same transition-state.

A Novel Method for Synthesis of Tetrahydropyrane and Piperidine Derivatives

Piperidine-4-ones and tetrahydropyrane-4-ones are important precursors for the synthesis of functionally substituted piperidines and tetrahydropyranes. In this study, the condensation of hexa-2, 4-diene and 2-methyl-penta-2, 4-diene with formaldehyde （reaction of oxymethylation） was investigated. The functionally substituted derivatives of piperidine and tetrahydropyrane were synthesized. The comparison of oxymethylation of dienes and 1-alkenes was showed, which indicates that the highest yield of tetrahydropyrane derivatives was achieved with 1-alkenes. This study provided theoretical basis for the synthesis of piperidine and tetrahydropyrane derivatives.

Anodic Cyanation of 1-(1-Methoxycarbonyl ethyl) piperidine

Aminonitriles were prepared efficiently from anodic cyanation of ?amino ester. The effect of different solvents and electrolytes was studied. The other byproducts were analyzed.

Continuous microflow visible-light photocatalytic N-formylation of piperidine and its kinetic study

N-formylation of amines,a class of synthetically important reactions,is typically conducted using metal catalysts that are relatively expensive or not readily available and usually needs harsh conditions to increase the reaction efficiency.Here,an efficient continuous microflow strategy was developed for the gas-liquid visible-light photocatalytic N-formylation of piperidine,which achieved a reaction yield of 82.97%and a selectivity of>99%at 12 min using cheap organic dye photocatalyst under mild reaction conditions.The influence of essential parameters,including light intensity,temperature and equivalents of the gas,additive and photocatalyst,on the reaction yield was systematically studied.Furthermore,kinetic investigations were conducted,exhibiting the dependence of reaction rate and equilibrium yield of N-formylpiperidine on light intensity,temperature and photocatalyst equivalent.The microflow photocatalytic approach established in this work,which realized a markedly higher space-time yield than the conventional batch method(37.9 vs.0.212 mmol h-1 L-1),paves the way for the continuous,green and efficient synthesis of N-formamides.

Identification of 2-aminothiazoyl piperidine derivatives as a new class of adjuvants potentiating the activity of colistin against Acinetobacter baumannii

The rapid prevalence of antibiotic resistance has led to a significant global health problem. Although colistin is the last resort antibiotic, it is limited by dose dependent toxicity. A critical approach to solve this problem is to use an antibiotic adjuvant, which is able to potentiate the activity of antibiotic and reduce the dosage of antibiotic. Herein, we reported a novel 2-aminothiazoyl piperidine adjuvant, which enhanced the activity of colistin against Acinetobacter baumannii(A. baumannii). Two pilot libraries of 40compounds were prepared and their adjuvant activities were evaluated. The most potential compound11j enabled to cause16-fold reduction in the minimum inhibitory concentration(MIC) of colistin at 8μg/m L. Besides, time-kill curves exhibited that compound 11j had significant adjuvant activity to kill the bacteria. The predicted ADMET analysis showed that 2-aminothiazoyl piperidine derivatives had good drug-likeness and acceptable physicochemical properties. Furthermore, membrane permeability experiments demonstrated that compound 11j was beneficial for colistin to destroy the outer membrane of bacteria. Also, the comparative molecular similarity indices analysis(Co MSIA) and the density functional theory(DFT) calculations were conducted. The results drawn from these analyses indicated that the novel scaffold provided helpful information for the finding of new adjuvant lead.

One-pot five-component synthesis of highly functionalized piperidines using oxalic acid dihydrate as a homogenous catalyst

An efficient green protocol is described for the preparation of highly functionalized piperidines via a one-pot five-component reaction between aromatic aldehydes,anilines andβ-ketoesters in the presence of oxalic acid dihydrate as catalyst in ethanol at ambient temperature.The structure as well as the relative stereochemistry of these compounds was confirmed by single X-ray crystallographic analysis.

Oxyfunctionalization of ketones bearing α-methylene group with piperidine oxoammonium salt.Synthesis of α-diketones from monoketones

A facile method for the title transformation is described. The reaction of 2,2,6,6-tetramethyl-4-methoxypiperidine oxoammonium chloride (1b) and ketones bearing a-methylene group in acetonitrile proceeded smoothly to give the a-oxyfunctionalized coupling products (6a-h). These coupling products decomposed upon heating in acidic medium to produce a-diketones (7a-h) in good to excellent yields.

Organocatalytically Enantioselective Approach to Polysubsti- tuted Tetrahydropyridines and Piperidines

A convenient and highly enanfioselecfive method for assembly of functionalized 1,2,3,4,5-pentasubstituted tetrahydropyridines and piperidines was developed. This method relies on preparing the required enantiopure cyclic semi-acetals via an organocatalyzed Michael addition/cyclization cascade reaction of aldehydes and a-keto-α,β- unsaturated esters, and subsequent reductive amination/condensation with primary amines.