- Preparation and animal biodistribution of 166Ho labeled DOTA for possible use in intravascular radiation therapy (IVRT)
-
Owing to its favorable decay characteristics (T1/2 = 27 h, Eβ(max) = 1.85 MeV, Eγ = 81 keV) and its availability with a specific activity of 3.74.4GBq/mg from a moderate flux reactor, 166Ho can be considered as a potential radionuclide for intravascular radiation therapy (IVRT) using liquid-filled balloons. In the present work, studies on the use of 166Ho labeled 1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a possible agent for IVRT for the prevention of restenosis has been initiated. 166Ho was obtained by irradiating natural Ho2O3 powder and DOTA was synthesized by a multistep procedure. The optimum protocol of radiolabeling of DOTA with 166Ho was achieved by varying different reaction parameters. The complex was found to retain its stability for 7 days at room temperature. Bioevaluation studies carried out in Wistar rats showed that >95% of the injected activity was excreted within 3 h p.i. with almost no retention in any major organ. Both radiochemical and biological studies showed that 166Ho labeled DOTA can be further explored as a potential agent for IVRT. Copyright
- Das, Tapas,Chakraborty, Sudipta,Banerjeel, Sharmila,Samuel, Grace,Sarma,Venkatesh, Meera,Pillai
-
-
Read Online
- A copper-cyclen coordination complex associated with a polyoxometalate anion: Synthesis, crystal structure and electrochemistry of [Cu(cyclen)(MeCN)] [W6O19]
-
The reaction between Cu(NO3)2?3H2O and a tetra-aza macrocycle, more specifically, cyclen in 1:1 MeCN-MeOH solvent mixture forms a Cu2+-cyclen coordination complex in situ, that has been reacted with an isopolyanion [W6O19]2- in a slow diffusion technique, resulting in the isolation of an ion-pair solid [Cu(cyclen)(MeCN)][W6O19] (1). Single crystal structural investigation on 1 shows a square pyramidal geometry around the metal centre (copper ion) with an axially bound MeCN solvent molecule. The title compound 1 is the first crystallographically characterized ion-pair compound, in which a transition metal coordination complex of a tetra-aza-crown ether (cyclen) has been associated with a polyoxometalate cluster anion. This communication deals with synthesis, spectroscopic, structural and electrochemical analyses of compound 1.
- Sarma, Monima,Chatterjee, Tanmay,Das, Samar K.
-
-
Read Online
- Isomerization kinetics of lanthanide(III) complexes with the pendant-arm macrocyclic ligand 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane
-
The 13C and 1H NMR spectra of the complexes of LaIII, EuIII and LuIII with 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane (L1) in acetonitrile or methanol indicated the presence of two enantiomers the interconversion of which proceeds through both a ring inversion and a rearrangement of the pendant arms. The following kinetic parameters were extracted from temperature-dependent 13C NMR spectra for the ring inversion in [LaL1]3+, [EuL1]3+, [LuL1]3+ in CD3OD and [EuL1]3+ in CD3CN:k(298 K) = 1396, 1055, 1288 and 880 s-1; ΔH? = 37.6, 41.1, 48.2 and 47.7 kJ mol-1; ΔS? = -58.5, -49.2, -23.8 and -28.4 J K-1 mol-1, respectively. The lanthanide(III) substitution induces a continuous variation of the kinetic parameters, implying the same pathway for the enantiomerization. The behaviour of [LnL1]3+ in solution is compared with that of complexes with similar 12-membered tetraaza macrocycles bearing pendant arms.
- Pittet, Pierre-Andre,Frueh, Dominique,Tissieres, Veronique,Buenzli, Jean-Claude G.
-
-
Read Online
- A practical synthesis of 1,4,7,10-tetraazacyclododecane, a pivotal precursor for MRI contrast agents
-
A practical preparation of the versatile macrocycle 1,4,7,10- tetraazacyclododecane (cyclen) was developed starting from cheap and easily available starting materials as ethylenediamine and glyoxal.
- Ferrari, Marinella,Giovenzana, Giovanni B.,Palmisano, Giovanni,Sisti, Massimo
-
-
Read Online
- A microcalorimetric determination of the enthalpies of formation in solution of nickel(II) complexes with tetraaza macrocyclic ligands of varying size
-
The enthalpies of formation of nickel complexes with tetraaza macrocyclic ligands of varying ring size, from 12 to 15 members, have been determined by destroying the complexes in aqueous solution with alkaline cyanide. The octahedral-square-planar equilibria have been investigated, and the results are presented as ΔH° for both octahedral, blue and, when possible, square-planar, yellow species. Like the Cu(II) system, the blue, octahedral series exhibits a maximum in ΔH° with [14]aneN4. This is discussed in terms of the relative size of the ligand and the metal ion. The unexpected reversal of ΔH° for the two square-planar complexes is rationalized in terms of expected ligand transformations.
- Fabbrizzi, Luigi,Micheloni, Mauro,Paoletti, Piero
-
-
Read Online
- A new, facile synthesis of 1,4,7,10-tetraazacyclododecane: Cyclen
-
This report outlines a new and efficient synthesis of cyclen (1,4,7,10-tetraazacyclododecane, 1) utilizing bis-imidazoline, 6 (1,1′-ethylenedi-2-imidazoline), with 1,2-dibromoethane. General conditions were developed, allowing for the simple, three-step synthesis of 1 at the multigram scale with an isolated overall yield approaching 65%. The cyclization of 6 produced by the condensation of triethylene tetraamine (TETA) with N,N-dimethylformamide dimethyl acetal, gave the twelve membered, imidazolinium, cyclized intermediate bromide salt, 7 (2,3,4,5,6,7,8,8c-octahydro-1H 4a,6a,8a-triaza-2a-azoniacyclopent[fg]acenaphthylene), which hydrolyzed to 1 with the use of hot, aqueous caustic. Hydrolysis of 7 under milder conditions formed the 1,4,7,10-tetraazabicyclo[8.2.1]-tridecan-13-one (20). Mechanistically, the formation of 7 may be rationalized as involving a diaminocarbene that undergoes an intramolecular carbon-hydrogen insertion.
- Athey, Phillip S.,Kiefer, Garry E.
-
-
Read Online
- DINUCLEATING LIGAND OR DINUCLEAR METAL COMPLEX
-
To provide a metal complex that has high cancer cell toxicity and has DNA target and cyclen.SOLUTION: The present disclosure provides a dinuclear metal complex represented by the following formula (IV).SELECTED DRAWING: None
- -
-
Paragraph 0058-0059
(2021/03/19)
-
- Preparation method of cyclen and intermediate thereof
-
The invention discloses a preparation method of cyclen and an intermediate thereof, specifically a preparation method of a compound as shown in a formula 4. The method comprises the following step: in water, carrying out a reduction reaction as shown in the specification on a compound as shown in a formula 3 and hydrazine hydrate, wherein X is phosphoric acid or sulfuric acid, when X is phosphoric acid, n is 4/3, and when X is sulfuric acid, n is 2. The preparation method has the advantages of low cost, simple operation, easy purification of intermediates and products, high yield and purity, and suitableness for industrial production.
- -
-
Paragraph 0121-0123
(2021/07/08)
-
- Preparation method of cyclen
-
The invention provides a preparation method of cyclen. The method comprises the following step: taking triethylenetetramine (TETA) as a raw material to carry out refining, then carrying out a reactionon the refined triethylenetetramine with methylglyoxal to obtain an intermediate 2, carrying out cyclization on the intermediate 2 with glyoxal, carrying out reducing with sodium borohydride to obtain a cyclized intermediate 3, finally carrying out ring opening through acid hydrolysis, and then adjusting the pH value by using an alkali solution to free out the cyclen.
- -
-
Paragraph 0061; 0062; 0063
(2020/02/14)
-
- Novel synthesis method of 1, 4, 7, 10-tetraazacyclododecane
-
The invention provides a novel synthesis method of 1, 4, 7, 10-tetraazacyclododecane. The 1, 4, 7, 10-tetraazacyclododecane has important application in biomedicine and molecular biology, molecular recognition, catalysis, enzyme chemistry, supramolecular chemistry, hydrogen storage materials and other main surfaces. The preparation method comprises the following steps of: reacting triethylene tetramine and urea serving as initial raw materials to generate ethylene bis-imidazolinone (hereinafter referred to as bis-imidazolinone), carrying out condensation reaction on the raw material and 1, 2-dihalogenated ethane to generate 1, 4-keto-7, 10-keto-1, 4, 7, 10-tetraazacyclododecan (hereinafter referred to as diketone cyclododecane), and preparing 1, 4, 7, 10-tetraazacyclododecane by hydrolysis. According to the method, the product with the gas chromatography content of 99% or above is obtained at the highest total yield of 74.97%. The method has the advantages of high atom utilization rate, few reaction steps, simplicity, easiness in control, high yield and the like, and is a new process route representing clean and efficient production.
- -
-
Paragraph 0029-0030
(2020/11/01)
-
- Preparation method of high-purity cycleanine
-
The invention discloses a preparation method of high-purity cycleanine. Diethylenetriamine and N-benzyl diacetaldehyde amine are used as main raw materials, a drying agent is added, generated water isabsorbed, the generation of imine is promoted, meanwhile, hydrogen is introduced to rapidly reduce the imine, the decomposition of imine is avoided, and the reaction is more thorough. The method is simple in step, low in cost, high in yield, low in equipment requirement, environmentally friendly and suitable for industrial production.
- -
-
Paragraph 0028-0031
(2020/04/06)
-
- Preparation method of cycleanine
-
The invention provides a preparation method of cycleanine, and belongs to the technical field of production and preparation of fine chemicals. The method comprises the following steps: 1) adding a solvent, a ring extender and an acid-binding catalyst into an intermediate bisimidazoline, and performing a reaction in an inert gas atmosphere for a period of time; 2) performing vacuumizing after the reaction is finished in order to remove light components, then adding water and an alkaline catalyst, raising the temperature, performing a reaction for a period of time, and performing vacuumizing toremove the light components; and 3) adding toluene, filtering out a product liquid while hot, and finally performing recrystallization with water-toluene to obtain the cycleanine final product. The intermediate bisimidazoline is prepared by taking toluene as a solvent and triethylenetetramine as a substrate, dropwise adding N,N'-dimethylformamide dimethyl acetal, and performing vacuumizing after the raw materials are dropwise added to extract light components so as to obtain a turbid liquid which is the intermediate bisimidazoline. A single kettle or a multi-kettle combined form can be adoptedin the preparation process of cycleanine, so that the one-time investment cost is reduced; and the solvent has the characteristics of low dosage, recycling realization and low loss.
- -
-
Paragraph 0031-0050
(2020/02/10)
-
- Method for preparing cyclen
-
The invention discloses a method for preparing cyclen. A reaction is carried out in a solvent by using ethylenediamine and dihaloethane as raw materials, a phase transfer reagent as a catalyst and cyclen generated by a reaction as an acid binding agent. The cyclen is obtained by treatment after the reaction is completed. The preparation of the cyclen by the method of the invention has the advantages of cheap and easily available raw materials, high yield, small pollution and simple operation, and overcomes the problems of the prior art that other acid binding agents are added for reaction, protection groups are required, and deprotection is carried out after the reaction is completed, and the protection and deprotection are complicated in process, low in yield, large in pollution and low in atomic utilization rate and the like.
- -
-
Paragraph 0039; 0040
(2019/08/06)
-
- NOVEL SYNTHESIS OF CYCLEN USING OXAMIDE AND LITHIUM ALUMINIUM HYDRIDE
-
The present invention relates to a novel method for synthesizing cyclen, which can provide a method for synthesizing cyclen without generating toxic substances using oxamide instead of a cyclen synthesis method, which previously has problems of generating hydrogen sulfide when manufacturing an intermediate compound using dithiooxamide. In addition, the novel method for synthesizing cyclen uses lithium aluminum hydride in the synthesis of cyclen from the intermediate compound, thereby being able to significantly shorten a reaction time compared to an existing method of using DIBAL-H.COPYRIGHT KIPO 2020
- -
-
Paragraph 0051-0057
(2019/12/15)
-
- BINUCLEATING LIGAND OR BINUCLEAR METAL COMPLEX
-
PROBLEM TO BE SOLVED: To provide a binuclear metal complex that can be easily synthesized and has a proper anticancer action. SOLUTION: The present invention provides a binuclear metal complex represented by the following chemical formula (IV). SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2018,JPOandINPIT
- -
-
Paragraph 0039; 0040
(2018/09/25)
-
- High-efficiency environment-friendly low-cost synthetic method of cycleanine
-
The invention discloses a high-efficiency environment-friendly low-cost synthetic method of cycleanine. The synthetic method comprises the following steps: step a, mixing triethylene tetramine, water,potassium carbonate and acetone to obtain a mixture, separately adding paratoluensulfonyl chloride into the mixture in different batches, and synthesizing a compound 2; step b, adding the compound 2and 1,2-dibromoethane into a solvent, and synthesizing a compound 3 in the presence of alkaline metal carbonate; step c, adding water and sulfuric acid into the compound 3, adding ethanol into a reaction product, precipitating, discharging, centrifuging, collecting a solid product, adding water and active carbon into the solid product, stirring, decoloring, centrifuging, collecting filtrate, adding hydrochloric acid, perfor ming salting-out crystallization, precipitating, discharging, centrifuging, collecting the solid product, and obtaining a compound 4; and step d, taking the compound 4 andan alkaline substance as raw materials, synthesizing a cycleanine crude product, extracting and purifying by virtue of methylbenzene-water, and obtaining the cycleanine. The high-efficiency environment-friendly low-cost synthetic method has the advantages of low cost, high efficiency, environmental friendliness.
- -
-
Sheet 0041; 0042
(2018/04/28)
-
- One-pot method used for synthesis of cycleanine
-
The invention discloses a one-pot method used for synthesis of cycleanine, and belongs to the technical field of organic intermediate synthesis. According to the one-pot method, diethylenetriamine anddiethanolamine are taken as reaction raw materials; in the presence of an acid binding agent, cyclization reaction with a protective agent benzenesulfonyl choride is carried out so as to obtain an intermediate; the intermediate is subjected to concentrated sulfuric acid deprotection so as to obtain cycleanine sulfate; cycleanine sulfate is subjected to neutralization reaction in toluene so as toobtain cycleanine. The one-pot method is invented based on improvement of a reported method, operation process is simplified, generation of a large amount of salt-containing waste water and waste residue is avoided, production cost is reduced, and the one-pot method is suitable for industrialized large-scale production of cycleanine.
- -
-
Paragraph 0023; 0024; 0025
(2018/10/19)
-
- Cycleanine production and purification method
-
The invention discloses a cycleanine production and purification method which includes the steps: cooling cycleanine production reaction liquid for the first time; filtering the cycleanine productionreaction liquid; cooling filtrate for the second time and then performing standing, crystallization, filtering and drying to obtain a cycleanine product. According to the cycleanine production and purification method, cycleanine product post-treatment purification operation steps are simplified, hot filtration is omitted, the potential safety hazards of operators are reduced, production operationsafety level is reduced, and the method is green and environmentally friendly. The obtained cycleanine product is high in purity and good in quality, medication safety is improved, and industrialization is facilitated.
- -
-
Paragraph 0062-0067
(2018/12/05)
-
- A high-purity torus cane rather method for the preparation of
-
The invention provides a preparation method of high-purity cyclen. The method comprises the following preparation paths. Cyclen obtained by the method of the invention has high purity. At the same time, the method greatly reduces the energy consumption and the power cost, and thereby reducing the raw material cost; the method greatly improves the reaction rate, reduces the catalyst amount and the reaction temperature, thereby shortening the consuming time of the process, and reducing the process cost; and the method greatly reduces the acid amount consumption, and thereby greatly reducing the equipment loss. The preparation method improves the production efficiency, and enables the product quality to reach more than 99.8%; hydrazine hydrate is used for replacing diethylenetriamine for a hydrolysis reaction, so the process is suitable for industrialized production. The method of the invention is environmentally friendly, is cost-saving, and is suitable for environment-friendly industrialization.
- -
-
-
- Interrogating the Role of Receptor-Mediated Mechanisms: Biological Fate of Peptide-Functionalized Radiolabeled Gold Nanoparticles in Tumor Mice
-
(Graph Presented) To get a better insight on the transport mechanism of peptide-conjugated nanoparticles to tumors, we performed in vivo biological studies of bombesin (BBN) peptide functionalized gold nanoparticles (AuNPs) in human prostate tumor bearing mice. Initially, we sought to compare AuNPs with thiol derivatives of acyclic and macrocyclic chelators of DTPA and DOTA types. The DTPA derivatives were unable to provide a stable coordination of 67Ga, and therefore, the functionalization with the BBN analogues was pursued for the DOTA-containing AuNPs. The DOTA-coated AuNPs were functionalized with BBN[7-14] using a unidentate cysteine group or a bidentate thioctic group to attach the peptide. AuNPs functionalized with thioctic-BBN displayed the highest in vitro cellular internalization (≈ 25%, 15 min) in gastrin releasing peptide (GRP) receptor expressing cancer cells. However, these results fail to translate to in vivo tumor uptake. Biodistribution studies following intravenous (IV) and intraperitoneal (IP) administration of nanoconjugates in tumor bearing mice indicated that the presence of BBN influences to some degree the biological profile of the nanoconstructs. For IV administration, the receptor-mediated pathway appears to be outweighed by the EPR effect. By contrast, in IP administration, it is reasoned that the GRPr-mediated mechanism plays a role in pancreas uptake.
- Silva, Francisco,Zambre, Ajit,Campello, Maria Paula Cabral,Gano, Lurdes,Santos, Isabel,Ferraria, Ana Maria,Ferreira, Maria Jo?o,Singh, Amolak,Upendran, Anandhi,Paulo, António,Kannan, Raghuraman
-
p. 1153 - 1164
(2016/05/19)
-
- Synthesis and relaxivity measurement of cyclen based magnetic resonance imaging (MRI) contrast agent
-
1, 4, 7, 10-teraazacyclododecane (cyclen) is a key macrocycle used for the synthesis of Magnetic Resonance Imaging (MRI) contrast agents. Substituting the hydrogen atoms (attached to the nitrogen atoms in the ring) of cyclen with suitable groups produce stable ligands. These ligands on complexation with Ln3+ ions lead to the formation of useful chelates. Cyclen is widely synthesized via Richman and Atkins method. Cyclen based ligand 1,4,7-tris(carboxymethyl)-10-(methyl,2-ethoxybenzoate)- 1,4,7,10-tetraazacyclododecane (DO3A-MEB) was synthesized in this work. It was subsequently coupled with Gd3+ ion to afford its stable complex. Relaxivity of the complex was measured by inversion recovery (IR) method and it was compared with that of the commonly used MRI contrast agent Gd-DTPA. Longitudinal relaxivity measurements indicated 128 % enhancement compared to Gd-DTPA.
- Ur Rashid, Haroon,Khan, Khalid,Yaseen, Muhammad,Hassan, Waseem,Naveed Umar, Muhammad
-
-
- Straightforward approach to efficient oxidative DNA cleaving agents based on Cu(ii) complexes of heterosubstituted cyclens
-
The Cu(ii) complexes of cyclen and two of its heterosubstituted analogues were shown to be efficient oxidative DNA cleavers. The reactivity strongly depends on the heteroatom inserted into the macrocycle (O > S > N). The Royal Society of Chemistry 2013.
- Hormann, Jan,Perera, Chrischani,Deibel, Naina,Lentz, Dieter,Sarkar, Biprajit,Kulak, Nora
-
supporting information
p. 4357 - 4360
(2013/04/24)
-
- A novel synthesis of 1,4,7,10-tetraazacyclododecane by the tandem reaction of a vinylsulfonium salt
-
1,4,7,10-Tetraazacyclododecane was synthesized through 4 steps by using easily available diphenylsulfonium triflate as a key annulation reagent. The reaction condition was very mild and the yield was high. After oxidation and hydrolysis, 1,4,7,10-Tetraazacyclododecane, which had been proven to be the pivotal precursor for a wide range of MRI contrast reagents, was produced in an overall yield of 31%.
- Huang, Rui,Xie, Chunsong,Huang, Lin,Liu, Jinhua
-
p. 195 - 198
(2013/07/26)
-
- Synthesis and characterization of binuclear Zn(II)-cyclen complexes bridged by α,ω-bis(4-methylphenoxy) alkanes
-
A series of novel α,ω-bis(4-methylphenoxy) alkane functionalized cyclen ligands were synthesized by the nucleophilic substitution reaction of 1,4,7-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane and α,ω-bis(4-bromomethylphenoxy) alkanes. The corresponding dimeric Zn(II)-cyclen complexes were obtained by reaction of these ligands with Zn(ClO4)2·6H2O. Ligands and complexes were characterized by FT-IR, 1H NMR, and elemental analysis. Springer Science+Business Media B.V. 2012.
- Wan, Fuxian,Li, Changcheng,Jiang, Lin,Li, Ying
-
p. 2085 - 2096
(2013/02/23)
-
- ARENE CONNECTED POLYAMINE MACRORING DERIVATIVES, PREPARATION METHODS AND PHARMACEUTICAL USES THEREOF
-
Abstract: The present invention relates to arene connected polyamine macrocyclic derivatives represented by general formula I, pharmaceutically acceptable salts or hydrates thereof which have anti-HIV activities, in which the definitions of substituents are as defined in the description; to preparation methods of the compounds of formula I; to pharmaceutical compositions containing the compounds of formula I or their pharmaceutically acceptable salts or hydrates; to the use of the compounds of formula I or their pharmaceutically acceptable salts or hydrates for the preparation of a medicament for the treatment and prevention of HIV-associated diseases.
- -
-
Page/Page column 27
(2010/04/24)
-
- Selective monoprotection of 1,4,7,10-tetraazacyclododecane via direct reaction with 4-nitrophenyl active esters
-
A simple, one-pot preparation of monoprotected 1,4,7,10-tetraazacyclododecanes via an efficient acylation reaction with 4-nitrophenyl active esters has been developed.
- Skwierawska, Anna M.
-
body text
p. 6308 - 6310
(2009/04/06)
-
- Synthesis and anti-protozoal activity of C2-substituted polyazamacrocycles
-
A focused library of C2-substituted-1,4,7,10-tetraazacyclododecanes was synthesised and the compounds were tested for their ability to kill trypanosome and malaria parasites. Several compounds showed significant in vitro activity and were selectively active against the parasites over human embryonic kidney cells used as a counter screen.
- Reid, Caroline M.,Ebikeme, Charles,Barrett, Michael P.,Patzewitz, Eva-Maria,Mueller, Sylke,Robins, David J.,Sutherland, Andrew
-
p. 2455 - 2458
(2008/09/21)
-
- Synthesis, characterisation and anti-protozoal activity of carbamate-derived polyazamacrocycles
-
A short, highly efficient approach for the synthesis of a novel class of polyazamacrocycles containing N-functionalised carbamate side-chains has been developed. The key steps involved a phase-transfer mediated macrocyclisation to form the ring system as well as a tin-catalysed reaction with isocyanates to introduce the carbamate side-chains. X-Ray crystallography confirmed successful formation of the 1,4,7,10-tetraazacyclododecane ring and N-functionalisation of all the amine centres. Preliminary testing of the biological activity of the compounds revealed significant anti-parasitic activity against bloodstream form African trypanosomes. The Royal Society of Chemistry.
- Wilson, Jennifer M.,Giordani, Federica,Farrugia, Louis J.,Barrett, Michael P.,Robins, David J.,Sutherland, Andrew
-
p. 3651 - 3656
(2008/09/21)
-
- New synthetic routes for 1-benzyl-1,4,7,10-tetraazacyclododecane and 1,4,7,10-tetraazacyclododecane-1-acetic acid ethyl ester, important starting materials for metal-coded DOTA-based affinity tags
-
Two improved routes to synthesize 1-benzyl-1,4,7,10-tetraazacyclododecane (6) and 1,4,7,10-tetraazacyclododecane-1-acetic acid ethyl ester (11) are described as well as the synthesis of 1-{2-[4-(maleimido-N-propylacetamidobutyl) amino]-2-oxoethyl}-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (17) and its Y, Ho, Tm, and Lu complexes. The 1H and 13C NMR spectra of the new compounds as well as the single crystal X-ray structure analyses of the intermediates 4-benzyl-1,7-bis(p-toluenesulfonyl) diethylenetriamine (3) and 1,4,7-tris(p-toluenesulfonyl)diethylenetriamine (7) are reported and discussed. The rare earth complexes of 17 have been characterized by 1H NMR spectroscopy and MALDI-TOF mass spectrometry.
- Kohl, Stephan W.,Kuse, Katharina,Hummert, Markus,Schumann, Herbert,Mügge, Clemens,Janek, Katharina,Wei?hoff, Hardy
-
p. 397 - 406
(2008/09/21)
-
- Method of preparing cis-8b-methyldecahydro-2a,4a,6a,8a-tetraazacyclopenta[fg] acenaphthylene, cis-decahydro-2a,4a,6a,8a-tetraazacyclopenta[fg] acenaphthylene, cyclene and functionalised cyclenes
-
A method of preparing cyclene having formula (I) from triethylenetetraamine having formula (VIII) or ethylenediamine having formula (VIII′) includes a series of steps. The first series of steps (I) includes a step A (one-pot preparation of the compound having formula (IIa) from the compound having formula (VIII)), followed by a step B (transforming the compound having formula (IIa) into cyclene having formula (I)). The second series of steps (II) includes a step C (preparing the compound having formula (IIb) from the compound having formula (VIII)), followed by a step D (transforming the compound having formula (IIb) into cylcene having formula (I)). The third series of steps (III) includes a step E involving the one-pot preparation of the compound having formula (IIa) from the compound having formula (VIII), followed by a step B involving the transformation of the compound having formula (IIa) into cyclene having formula (I).
- -
-
Page/Page column 3; 7
(2010/11/23)
-
- Cyclohexanedione bisaminals as intermediates for cyclen, homocyclen, and cyclam synthesis
-
A new easy-to-run route to cyclen, homocyclen, and cyclam is proposed, based on the cyclization with dibromo- or ditosyloxy-derivatives of bisaminal intermediates obtained by condensation of the appropriate linear tetraamine with cyclohexanedione. In the cyclization step, the use of cesium carbonate instead of potassium carbonate as proton trapper caused a remarkable increase of yields. Copyright Taylor & Francis Group, LLC.
- Prokhorov, Anton,Le Bris, Nathalie,Bernard, Helene,Claudon, Geraldine,Handel, Henri
-
p. 3271 - 3282
(2007/10/03)
-
- A PROCESS FOR THE PREPARATION OF TETRAAZAMACROCYCLES
-
A process for the preparation of tetraazamacrocycles of general formula (I) wherein n, p and q can independently be 0 or 1, comprising the following steps: a): condensation of polyamines with a glyoxal derivative; b): condensation of the resulting compound with an alkylating agent; c): oxidation of the resulting compound with an oxidizing agent, to give a mixture of oxidated products which is submitted to d): hydrolysis in acid aqueous solution, to give the compound of formula (I).
- -
-
-
- Preparation of N-arylmethyl aziridine derivatives, 1,4,7,10-tetraazacyclododecane derivatives obtained therefrom and N-arylmethyl-ethanol-amine sulphonate esters as intermediates
-
PCT No. PCT/GB96/00552 Sec. 371 Date Dec. 2, 1997 Sec. 102(e) Date Dec. 2, 1997 PCT Filed Mar. 8, 1996 PCT Pub. No. WO96/28420 PCT Pub. Date Sep. 19, 1996Aziridines may be subjected to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I) where each R1 is independently hydrogen or a group AR and Ar is an optionally substituted phenyl group. The process comprises reacting a purified N-arylmethylethanolaminesulphonate ester with a base. N-arylmethyl-ethanolamine sulphonate ester of the formula R'NHCH2CH2OSO3H, wherein the N-arylmethyl group R' is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect, the invention provides compounds of formula (II) where Ar and R1 are as hereinabove defined and at least two differing ArCHR21 moieties are present.
- -
-
-
- Process for the preparation of tetraazamacrocycles
-
PCT No. PCT/EP98/01882 Sec. 371 Date Aug. 11, 1999 Sec. 102(e) Date Aug. 11, 1999 PCT Filed Apr. 1, 1998 PCT Pub. No. WO98/45296 PCT Pub. Date Oct. 15, 1998Procedures for preparing compounds of formula (I) in which n, p and q or independently 0 or 1, are prepared according to the reaction scheme:
- -
-
-
- Condensation of glyoxal with triethylenetetraamine; isomerization and cyclization
-
The condensation of triethylenetetraamine with glyoxal leads to the formation of four stereoisomers A, B, C, D. A is the thermodynamic product and D the kinetic one. These four compounds exhibit equilibrium and isomerization phenomena which are the key-feature of this cyclen synthesis.
- Hervé, Gwéna?lle,Bernard, Hélène,Toupet, Lo?c,Handel, Henri
-
-
- Process for the preparation of tetraazamacrocycles
-
A process for the preparation of tetraazamacrocycles of general formula (I) STR1 wherein n, p and q can independently be 0 or 1, comprising the following steps: a): condensation of polyamines with a glyoxal derivative; b): condensation of the resulting compound with an alkylating agent; c): oxidation of the resulting compound with an oxidizing agent, to give a mixture of oxidated products which is submitted to d): hydrolysis in acid aqueous solution, to give the compound of formula (I).
- -
-
-
- Process for the preparation of 1,4,7,10-tetraazacyclododecane
-
A process for the preparation of 1,4,7,10-tetraazacyclododecane of formula (I), starting from decahydro-2a,4a,6a,8a-tetraazacyclopent?fg!acenaphthylene of formula (II): comprising the direct step of hydrolysis in aqueous solution, in conditions of slightly acid, neutral or slightly basic pH, with a primary diamine of formula (V), in which x ranges between 0 and 2, and Q is --CH2 CH(OH)CH2 --, --(CH2)2 NH(CH2)2 --, or --?(CH2)2 NH!2 (CH2)2, when x is 1, or Q is --CH2 -- when x is 2. STR1
- -
-
-
- Synthesis of dicarboxymethyl tetraazacyclododecane derivatives for polycondensation
-
Three different routes to synthesize selectively protected tetraaza macrocycles bifunctionalized with carboxymethyl acid groups have been developed in order to obtain monomers for polycondensation. The first way has been carried out from cyclen, whose synthesis has been improved, requires 6 steps. The second way allowed to obtain the bifunctional protected macrocycle from ethylenediamine and diethyl iminodiacetate in 2 steps. The last way has consisted in synthesizing directly a monomer by cyclization from ethylenediaminetetraacetic acid bisanhydride and ethylenediamine.
- Montembault,Mouaziz,Blondeau,Touchard,Soutif,Brosse
-
p. 4279 - 4294
(2007/10/03)
-
- Hydrazide derivatives of polyamides and their medical use as chelating agents
-
The invention relates to certain substituted derivatives of aminopolycarboxylic acids and metal chelates thereof. The compounds are particularly suitable for use as diagnostic agent. For example, the compounds can be used as radiodiagnostic agents, detoxification agents and contrast agents for diagnostic imaging processes. In particular, the high relaxivity paramagnetic metal chelates of substituted aminopolycarboxylic acids are especially suited for use as magnetic resonance imaging contrast agents.
- -
-
-
- Polyazamacrocyclofluoromonoalkylphosphonic acids, and their complexes, for use as contrast agents
-
Polyazamacrocyclofluoromonoalkylphosphonic acid compounds are disclosed which form inert complexes with Gd, Mn, Fe or La ions. The complexes are useful as contrast agents for diagnostic purposes.
- -
-
-
- Process for tetraazacycloalkane preparation
-
The present invention provides a synthetic route for tetraazacycloalkane preparation which facilitates heteropoly-N-alkylation of the macrocyclic product, and is thereby beneficial for the production of chelating agents and chelates useful in diagnostic imaging. The process involves (i) reacting a tetraazaalkane with a bridging agent to couple four amine nitrogens of said tetraazaalkane to a bridging moiety to yield a fused tricyclic intermediate, (ii) reacting said intermediate to introduce an alkylene bridge between the secondary amine nitrogens in the outer rings of the fused tricyclic intermediate, optionally by decoupling an alkanediylidene bridging moiety from the tertiary amine nitrogens at the ring fusion sites of the fused tricyclic intermediate, and (iii) where necessary, decoupling said bridging moiety to yield a macrocyclic tetraazacycloalkane.
- -
-
-
- Synthesis and characterization of various unsubstituted and mono-N-substituted tetraazamacrocycles
-
Syntheses of tetraazamacrocycles have been carried out by using p-toluenesulfonyl chloride as protective group.The and were also obtained by the template synthesis.Mono-N-functionalization of tetraazamacrocycles was accomplished by reaction of a fivefold excess of the free macrocycles with 1 equivalent of a suitable alkylating or arylating reagent.The key point of the synthesis lies in the use of an excess of the macrocycle over the substituting reactants to reduce the formation of polysubstituted derivatives, and in the easy separation of the excess of unreacted macrocycle.All the products were characterized on the basis of spectral studies (1H and 13C NMR, including 2D NMR and NOE difference studies) and mass spectrometry.Key words: tetraazamacrocycles, improved synthesis, protective group, N-tosylation, template synthesis, NOE difference spectroscopy.
- Meunier, I.,Mishra, A. K.,Hanquet, B.,Cocolios, P.,Guilard, R.
-
p. 685 - 695
(2007/10/02)
-
- Cascade polymer bound chelating compounds, their chelates and conjugates, processes for their production, and pharmaceutical agents containing them
-
Cascade polymers, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as, if desired, cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable complexing compounds and complexes for diagnostics and therapy.
- -
-
-
- Macrocyclic chelating agents and chelates thereof
-
Macrocyclic derivatives of 1,4,7,10-tetraazacyclododecane of general formula (I) hereinbelow, wherein A is a group of formula (II) hereinbelow, in which R is H or alkyl or optionally substituted benzyl or a H(OCH2 CH2)1-4-, Me(OCH2 CH2)1-4-, or Et(OCH2 CH2)1-4- group, X or O--R1, in which R1 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group or X is --NR2 R3, in which R2 and R3 are H or alkyl, hydroxyalkyl, alkoxyalkyl or alkoxyhydroxyalkyl, and B1, B2 and B3 have the same meanings as A or are H or a group of formula (III) hereinbelow, in which R4 is H or alkyl, Y is a O--R5 group, wherein R5 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group, or Y is a --NR6 R7 group, wherein R6 and R7 are H or alkyl, hydroxyalkyl, alkoxyalkyl, or alkoxyhydroxyalkyl, said derivatives optionally being salified, and the complex salts thereof, are used as pharmaceuticals and/or diagnostic agents. STR1
- -
-
-
- MACROHETEROCYCLES. 15.* SYNTHESIS OF MACROCYCLIC POLYAMINES IN A BIPHASIC SYSTEM
-
Macrocyclic polyamines are conveniently synthesized by condensation of bissulfonamides with ditosylates or dibromides of glycols in the biphasic system toluene(xylene)-aqueous sodium hydroxide.
- Luk'yanenko, N. G.,Basok, S. S.,Filonova, L. K.,Kulikov, N. V.,Pastushok, V. N.
-
p. 346 - 349
(2007/10/02)
-
- Macrocyclic chelating agents and chelates thereof
-
Macrocyclic derivatives of 1,4,7,10-tetraazacyclo-dodecane of general formula I wherein, A is a group of formula in which, R is H or alkyl or optionally substituted benzyl or a H(OCH2CH2)1 4-, Me(OCH2CH2)1 4-, or Et(OCH2CH2)1 4- group,X is O-R1, in which R1 is H or alkyl, hydroxyalkyl, alko-xyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group or X is -NR2R3, in which R2 and R3 are H or alkyl, hydroxyalkyl, alkoxyalkyl or alkoxyhydroxyalkyl,and, B1, B2 and B3 have the same meanings as A or are H or a group of formula in which, R4 is H or alkyl, Y is a O-R5 group, wherein R5 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group, or Y is a -NR6R7 group, wherein R6 and R7 are H or alkyl, hydroxyalkyl, alkoxyalkyl or alkoxyhydroxyalkyl, said derivatives optionally being salified, and the complex salts thereof, are used as pharmaceuticals and/or diagnostic agents.
- -
-
-
- MACROHETEROCYCLES. PART 44. FACILE SYNTHESIS OF AZACROWN ETHERS AND CRYPTANDS IN A TWO-PHASE SYSTEM
-
A facile procedure is proposed for the preparation of azacrown ethers and cryptands by condensation of dibromides or ethylene glycol bis(toluene-p-sulphonate)s with acyclic bis(sulphonamide)s or with bisdiazacrown ethers, respectively.The reaction was carried out in a two-phase system of aqueous alkali-toluene (benzene)in the presence of quaternary ammonium salts as phase transfer catalysts.The catalytic activity decreased in the sequence: Bu4NI ca.Bu4NBr > Bu4NCl > Bu4NHSO4 > Et3NCH2C6H5NCl.Maximum yields of twelve-membered azacrown ethers are obtained when lithium hydroxide is used, while crown ethers of larger size are observed in the presence of sodium or potassium hydroxides; this may be due to a template effect.
- Lukyanenko, Nikolai G.,Basok, Stepan S.,Filonova, Lyubov K.
-
p. 3141 - 3148
(2007/10/02)
-