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.

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.

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.

Novel 2-aryl-3,4,5-trihydroxypiperidines:Synthesis and glycosidase inhibition

Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines （6-8 and their enantiomers）, the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six- membered cyclic nitrones through a concise two-step procedure, i.e., Grignard reagent addition and deprotection. These novel polyhydroxylated piperidine iminosugars were assayed against 10 types of enzymes. Only compound 8 exhibited weak inhibition （IC50 1080 μmol/L） against β-galactosidase from rat intestinal lactases.

Synthesis and Crystal Structure of a Genistein-derived Compound

A genistein derivative, 5-hydroxy-3-（4-hydroxyphenyl）-7-（2-（piperidin- 1-yl）ethoxy）- 4H-chromen-4-one 3, was designed, prepared and structurally characterized by single-crystal X-ray diffraction. X-ray structure analysis reveals that 3 crystallizes in the orthorhombic system, space group Pbca, with a = 16.238（3）, b = 10.308（2）, c = 22.987（5）A, V = 3847.6（13）A3, Z = 8,μ= 0.093 mm^-1, Dc = 1.317 g/cm^3, F（000） = 1616, R = 0.0789 and wR = 0.1554 for 1463 observed reflections with I 〉 2σ（I）.

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.

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.

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.

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.

Toxicity of newly isolated piperideine alkaloids from the red imported fire ant, Solenopsis invicta Buren, against the green peach aphid, Myzus persicae (Sulzer)

The green peach aphid, Myzuspersicae (Sulzer), is a major insect pest of many agronomic and horticultural crops and is distributed worldwide. Aphid management is often based on application of insecticides. However, the aphid is now resistant to many of these and much interest has recently developed in identification of novel alternative insecticides. Venom isolated from the red imported fire ant, Solenopsisinvicta Buren, is composed of two groups of alkaloids, piperidines and piperideines, and has shown activity against many organisms including fungi, bacteria, mites and several insects. Prior to the study reported herein, no information on the venom’s activity to Myzuspersicae has been reported. Both of the alkaloids were active against M.persicae. The 24 h LC50 values were116.6 and 91.5 ppm for the piperideine and piperidine extracts, respectively. Based on overlap of the 95% fiducial limits the LC50 values for the two alkaloids did not significantly differ. At the high dosages, mortality occurred in as few as four hours and all treated aphids were dead by six hours. Little additional mortality was detected in the 48-hobservation. Both piperideine and piperidine extracts isolated from red imported fire ant venom possess sufficient activity to cause death of green peach aphids and at high dosages, death occurs rapidly. In the search for new replacements to synthetic insecticides, these extracts may offer a novel but potentially successful alternative.