Bridgehead Nitrogen Atoms Research Articles

Recent Progress in the Pharmacology of Imidazo[1,2-a]pyridines

Imidazo[1,2-a]pyridine is a bicyclic system with a bridgehead nitrogen atom, of growing interest in medicinal chemistry. The paper deals with the recent progress realised in the comprehension of the pharmacological properties of this scaffold. From the many imidazo[1,2-a]pyridine analogues described in the literature, those discussed herein will be presented in three parts concerning first the enzyme inhibitors, then the receptor ligands and finally the anti-infectious agents.

Host–Guest Complexes of Oligopyridine Cryptands: Prediction of Ion Selectivity by Quantum Chemical Calculations

AbstractThe structures and complex‐formation energies for the cryptands 6,6′,6″,6″′,6″″,6″″′‐bis[nitrilotri(methylene)]tris(2,2′‐bipyridine) (1) and 2,2′,2″,9,9′,9″‐bis[nitrilotri(methylene)]tris(1,10‐phenanthroline) (2) with alkali and alkaline‐earth cations are obtained by PM3/SPASS and density functional (B3LYP/LANL2DZp) calculations and the results used to predict the ion selectivity. Both cryptands 1 and 2 have a cavity size similar to [2.2.2] and prefer Ca2+ and Sr2+, while 1 has a preference for K+ and 2 favours Na+ and K+. The cryptand flexibility for 1 is attributed mainly to the bipyridine building block and that for 2 to the groups neighbouring the bridgehead nitrogen atoms. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Heterocyclic System Containing Bridgehead Nitrogen Atom: Synthesis and Pharmacological Activities of Some Substituted 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Recent Advances in the Area of Pyridodiazinium Systems Containing a Bridgehead Nitrogen Atom

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis and novel fluorescence phenomenon of terbium complex with a new Schiff base ligand derived from condensation of triaminotriethylamine and 3-indolemethanal

A new Schiff base ligand with tripodal structure, N, N′, N″-tri-(3-indolemethanal)-triaminotriethylamine (L), and its complex with terbium was synthesized. The complex was characterized by element analysis, IR spectra, mass spectra, thermal analysis and molar conductivity. The terbium ion was found to coordinate to the Schiff base nitrogen atoms and the bridgehead nitrogen atom. The fluorescence properties of the complex in aqueous solutions were studied. Under the excitation of UV light, the complex exhibits characteristic fluorescence of terbium ion. H + concentration could strongly enhance the luminescence of terbium complex with L in aqueous solutions. This phenomenon will make the new complex favorable to be used in the fluorescence switches and sensors. The mechanism of the fluorescence enhancement by protonation of the indole nitrogen atoms is due to the suppressed photoinduced electron transfer (PIET) fluorescence quenching when adding acid.

Synthesis of thioswainsonine as a potential glycosidase inhibitor

The synthesis of a bicyclic sulfonium-ion analogue of a naturally occurring glycosidase inhibitor, swainsonine, in which the bridgehead nitrogen atom is replaced by a sulfonium ion, has been achieved by a multi-step synthesis starting from 1,4-anhydro-2,3-di- O-benzyl-4-thio- d-lyxitol. The synthetic strategy relies on the intramolecular displacement of a leaving group on a pendant acyclic chain by a cyclic thioether. This bicyclic sulfonium salt will serve as a candidate to test the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor.

Alteration in the Binding Property of a Laterally Nonsymmetric Aza Cryptand toward CuII, AgI, and TlIIons upon Derivatization with a Cyanomethyl Group

AbstractThe laterally nonsymmetric aza cryptandLoreadily forms mononuclear inclusion complexes with metal ions like CuII, NiII, AgI, TlI, and so forth. However, when the secondary amines present in the three bridges are substituted by a cyanomethyl group to yield a new cryptandL, its metal‐binding properties are drastically altered. Thus, whileLobinds AgIat the tren end, showing AgN4coordination, inL, the bridgehead nitrogen atoms are pulled inside to form a two‐coordinate complex of AgIand none of the O or N atoms present in the three bridges are involved in coordination. This is probably the first example where the two bridgehead atoms are pulled inside to the maximum to bind the metal ion. Likewise, the TlIion shows TlN4coordination withLo, while inLit is loosely bound at the tren end, showing TlN3coordination. Upon treatment with a AgIsalt, the TlIcan be replaced almost instantaneously. On the other hand, with copper(II) tetrafluoroborate salt in moist DMF, two of the cyanide groups inLare converted to carboxylic acid groups and bind the metal ion from outside. The CuIIion in this complex shows distorted octahedral coordination where the two O atoms from the two carboxylic acid groups and the two corresponding N atoms in the two bridges are bound equatorially. The two axial sites are occupied by the nearby bridgehead N atom and the O atom of a DMF molecule. All five complexes and the free ligands are characterized by spectroscopic and X‐ray crystallographic studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Recent Advances in the Area of Pyridodiazinium Systems Containing Bridgehead-Nitrogen Atom

Recent Advances in the Area of Pyridodiazinium Systems Containing Bridgehead-Nitrogen Atom

Synthesis and Properties of Cryptands with a Thioether Bridge and π‐Donors – Silver(I) and Copper(I)‐Complexes

AbstractThe syntheses of seven bridgehead diazabicycloalkanes are reported. The bridges are represented by either a thioether chain and two 3‐hexyne units (4 and 6–8), one selenoether chain and two 3‐hexyne units (5), or one dithioether chain and two 4,4′‐diethylbiphenyl units (9, 10). X‐ray investigations reveal for 4–10 the in/in conformation at the bridgehead nitrogen atoms. Reactions with CuI triflate yield the endohedral CuI complexes of 4–6. Endohedral complexes of 6, 7, and 10 were isolated with silver triflate. X‐ray investigations and spectroscopic studies on the metal complexes reveal interactions between the metal ion and the nitrogen‐, chalcogen‐, and π‐units. In addition to the bicyclic systems 4–10 we synthesized the tripodal systems 28–33 in a one‐pot reaction. In the cases of 28 and 33 we were able to isolate the corresponding AgI complexes. X‐ray studies show an interaction between the metal ion and the nitrogen atom and one double bond of each of the three adjacent phenyl rings. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Synthesis of a Sulfonium Ion Analogue of the Glycosidase Inhibitor Swainsonine

The synthesis of a bicyclic sulfonium ion analogue of a naturally occurring indolizidine alkaloid, swainsonine, in which the bridgehead nitrogen atom is replaced by a sulfonium ion, has been achieved by a multistep synthesis starting from (2S,3S,4R)-2,3-dibenzyloxy-4-formaldehyde-thiolane. The synthetic strategy relies on the intramolecular displacement of a leaving group on a pendant acyclic chain by a cyclic thioether. This bicyclic sulfonium salt provides a candidate with which to further probe the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor.

Heterocycles with a Bridgehead Nitrogen Atom. Part 16. Assembly of a peri‐Fused System from an Angular Tricycle by Recyclization of an Oxazole Ring into Pyrrole One.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Fused Quinolizine Derivatives by Condensation of Cyclic Schiff Bases with β-Keto Esters

A new procedure has been developed for the synthesis of fused nitrogen-containing heterocycles having a bridgehead nitrogen atom via condensation of cyclic Schiff bases with β-keto esters.

Synthesis of 4,7,13,16,21,24-hexaoxa-1,10-diazoniabicyclo[8.8.8]hexacosane Dinitrate Hydrate and Its Disordered Crystal Structure

4,7,13,16,21,24-Hexaoxa-1,10-diazoniabicyclo[8.8.8]hexacosane dinitrate hydrate [H2(Crypt-222)]2+⋅2NO 3 − ⋅H2O is prepared as a crystalline salt and studied by single crystal X-ray diffraction. In its crystal structure the 2,2,2-cryptand dication is disordered and has two different conformations with 55.3 and 44.7% probabilities. Hydrogen atoms of this dication at the two protonated bridgehead nitrogen atoms are directed inside the cavity. One of two NO 3 − anions is also disordered and has two different orientations with 77 and 23% probabilities. Geometric parameters of the molecular ions and water molecule (bond lengths, bond angles, etc.) are determined with a reasonable accuracy, and their packing in the crystal structure is established.

Synthesis and Conformational Analysis of Bicyclic Sulfonium Salts. Structures Related to the Glycosidase Inhibitor Australine

The syntheses of eight sulfonium compounds with structures related to the naturally occurring pyrrolizidine alkaloid, australine, in which the bridgehead nitrogen atom is replaced by a sulfonium ion, are described. The synthetic strategy relies on the intramolecular attack of a cyclic thioether across a terminal double bond in the presence of a suitable electrophile. We postulate that these compounds, having a permanent positive charge on the sulfur atom, will mimic the highly unstable oxacarbenium ion transition state in a glycosidase-catalyzed hydrolysis reaction. The conformational preferences of these compounds, based on analysis of 1H-1H vicinal coupling constants and 1D-NOESY data, are attributed to both steric and electrostatic interactions. These compounds will be used in the study of structure-activity relationships with glycosidase enzymes.

Mono‐, Di‐ and Polymeric Calcium and Gadolinium Complexes of the Tripodal Ligand 2,2′,2′′‐Nitrilotribenzoic Acid

AbstractThree novel carboxylate‐bridged complexes incorporating the tripodal N,O ligand 2,2′,2′′‐nitrilotribenzoic acid H3L of formula [CaII(H2L)(OH2)4][(H2L)]·4H2O (1), [CaII(OH2)4]‐[CaII(L)(OH2)2]2·7H2O (2) and [GdIII(L)(OH2)3]2[GdIII(L)‐(OH2)4]2·13H2O (3) were synthesized and characterized by X‐ray crystallography. In all three complexes, the ligand H3L binds to the metal centre only by its three carboxylate donors, leaving the bridgehead nitrogen atom nonbonding. The calcium(II) ion in the monomeric complex 1 is distorted pentagonal‐bipyramidal coordinated, the +1 charge of the complex cation [CaII(H2L)(OH2)4]+ is balanced by an H2L– anion and both units are connected by hydrogen bonds. The polymeric compound 2 displays a one‐dimensional chain structure, in which two [CaII(L)]2– units form a dimeric structure and are connected by hydrated CaII ions. 3 contains two different [GdIII(L)(OH2)n] dimers. In one of them the two GdIII ions are linked by two monoatomic carboxylate O‐bridges showing a short Gd···Gd distance of 3.99 Å. In the second, a syn‐anti carboxylate 1,3‐bridge with a longer Gd···Gd distance of 4.96 Å is observed. Magnetic measurements of 3 show paramagnetic behaviour with weak antiferromagnetic coupling. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Heterocycles with a bridgehead nitrogen atom. 16. Assembly of a peri-fused system from an angular tricycle by recyclization of an oxazole ring into pyrrole one

An unusual example of the recyclization of the tricyclic 6,7,8,9-tetrahydrooxazolo[3,2-a]quinolinium system into the 8,9-dihydro-7H-pyrrolo[3,2,1-ij]quinoline system was discovered. The reaction is a topological modification of the known conversion of oxazolo[3,2-a]pyridinium salts into indolizines. The structural feature of this transformation is a change of the annelation type in the tricycle from the angular one to peri-fusion of three rings.

Synthesis of some new pyridazine, 1,2,4-triazine and 1,3,4-thiadiazole derivatives

3-(2-Furyl)-3-oxo-propanenitrile (1) reacts with some phosphorus ylides to afford new pyridazine and 1,2,4-triazine derivatives. Reaction of 1 with some heterocyclic diazonium salts afforded fused heterocyclic systems with bridgehead nitrogen atoms.

Simultaneous freezing of chirality and in-out conformation of a macropentacyclic cryptand by protonation.

Compound 1, a cryptand-derived macropentacycle, is a flexible molecule that encompasses many conformations (symmetrical, unsymmetrical, and chiral ones) depending on the observation temperature (VT 1H NMR). Selective monoprotonation of this molecule leads to a totally unsymmetrical, rigidly chiral species in solution (1H NMR). Helical chirality and in-out conformation of monoprotonated 1 are observed in the solid state by X-ray diffraction analysis, as well as the proton location. The latter is bound to the endo bridgehead nitrogen atom and involved in hydrogen-bonding interactions with the three closest sulfurs. Significant induction of chirality is triggered by reaction of 1 with the optically active (R)-(-)-1,1'-binaphthyl-2,2'-diylphosphoric acid. It proceeds with a maximum 24% diastereomeric excess, as shown by the splitting, in the 62:38 intensity ratio, of several 1H NMR signals. These correspond to the two indistinguishable diastereomeric ion pairs: (Lambda-[1-H])((R)-(-)-BNP) and (Delta-[1-H])((R)-(-)-BNP).

Crystal Structure of 4,7,13,16,21,24-Hexaoxa-1,10-diazoniabicyclo[8.8.8]hexacosane Diiodide

The disordered crystal structure of 4'7'13'16'21'24-hexaoxa-1'10-diazoniabicyclo[8.8.8]hexa-cosane diiodide, [H2(2.2.2-Crypt)]2+·2I-, was studied by single crystal X-ray diffraction. The 2.2.2-cryptanddication is disordered, exists in the form of two different conformers A, B randomly occupying thesame place in the unit cell with 71.5 and 28.5% probability, respectively. In both conformers A and B, thehydrogen atoms at the bridgehead nitrogen atoms are directed inside the cavity (crypta) of the conformer. The geometric parameters (bond lengths, bond angles, torsion angles) of these conformers were found, and the packing of these cations and iodide anions in the crystal were determined. The iodide anions have contacts only with the methylene hydrogen atoms of conformers A and B.

Heterocyclic Synthesis Containing Bridgehead Nitrogen Atom: Synthesis of 3‐[(2H)‐2‐Oxobenzo[b]pyran‐3‐yl]‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazine and Thiazole Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.