Electron impact mass spectrometry of some macrocyclic polyether lactones

Electron impact mass spectrometry has been used together with linked scans, exact mass measurements and mass-analysed ion kinetic energy spectrometry to study nine inacrocyclic polyether lactones in detail. The presence of abundant hydrogenated oxirane ions has been observed for all the compounds examined, and confirmed by kinetic energy release measurements.     

Novel 2,4-methanoadamantane-benzazepine by domino photochemistry of N-(1-adamantyl)phthalimide

The photochemical reaction of N-(1-adamantyl)phthalimide (1) gives cleanly one product, the novel hexacyclic benzazepine derivative of 2,4-methanoadamantane 2. Its structure was characterized by spectroscopic methods and X-ray analysis and represent the first example of the 2-azahexacyclo[8.7.1.1 (1,4).0 (4,9).0 (11,16).0 (12,18)]nonadeca-4,6,8-triene skeleton. The product is formed by a domino process of two consecutive excited-state intramolecular gamma-hydrogen-transfer reactions. Base hydrolysis of the benzazepine 2 gives in high yield the keto derivative of the 1,2-substituted adamantane epsilon-amino acid 3.     

Proton-ionizable crown compounds. 4. New macrocyclic polyether ligands containing a triazole subcyclic unit

A series of macrocyclic polyether (crown) ligands containing the proton-ionizable s-triazole subcyclic unit were prepared by reacting the 1-THP blocked 3,5-bis(chloromethyl)-1H-1,2,4-triazole with various oligoethylene glycols. The starting bis(chloromethyl)triazole is a vessicant and must be used with caution. Triazolo-18-crown-6 ( 5 ) formed stable complexes with barium, strontium, copper and benzylammonium cations but not with potassium or lithium. The crystal structure of 5 showed the triazole proton to be on nitrogen 3 which is outside the macroring cavity.     

Synthesis of macrocyclic polyethers and polyether diesters and preparation of their cationic complexes

New macrocyclic polyethers, 2,3,5,6-bis-[5′(5′)-chlorobenzo]-1,7,10-trioxacyclododeca-2,5-diene (I), 2,3,5,6-bis-[5′(5′)-chlorobenzo]-1,7,10,13-tetra oxacyclo pentadeca-2,5-diene (II), and 2,3,5,6-bis-[5′(5′)-chlorobenzo]-1,7,10,13,16-penta oxa cyclo octadeca-2,5-dien (III), and macrocylic lactones 2,3,5,6-bis-[5′(5′)-chlorobenzo]-1,7,10,13-tetraoxacyclopentadeca-2,5-diene-8,15-dione (IV) and 2,3,5,6-bis[5′(5′)-chlorobenzo]-1,7,10,13,16-pentaoxacyclooctadeca-2,5-diene-8,18-dione (V) were synthesized. Complexes of ligands III and V with metal cations were prepared. Furthermore, their metal-picrate extraction with some metal salts was attempted. Structures of the ligands and complexes were confirmed using spectroscopic techniques.     

The synthesis and membrane transport characteristics of macrocyclic polyether ligands composed of 1,10-phenanthroline as carriers for primary amine species

Four macrocyclic polyether derivatives of o-phenanthroline were synthesized and used as neutral carriers for preparing poly(vinyl chloride) (PVC) membrane electrodes to sense primary amine species. The potentiometric response characteristics of the electrodes prepared were investigated. The electrode sensitive to benzyl amine as model analyte showed a linear response range of 8.0 x 10(-6)-0.1 mol/l with a detection limit of 8.9 x 10(-7) mol/l and a slope of 56.5 mV/decade. The linear potentiometric response of the mexiletine-sensitive electrode was 4.7 x 10(-6)-0.1 mol/l, and the detection limit was 5.0 x 10(-7)1 mol/l with a slope of 59.0 mV/decade. The transfer behavior of amines and ammonium ions through an organic phase was investigated by means of the bulk liquid membrane transport experiment. The effects of pH, counter anions and other factors on the transfer of the amine and ammonium species were studied. The mass transfer rates of the test species facilitated by macrocyclic polyether derivatives of o-phenanthroline were determined and the following sequence was found: benzyl amine > ethyl amine > tetramethyl ammonium > triethyl amine > diethyl amine > K(+) > ammonium > Na(+) > Ca(2+) > Mg(2+). This was exactly the potentiometric selectivity sequence of the membrane electrodes prepared by using these carriers. The mechanism of transfer of benzyl amine through a membrane phase induced by the carriers has been elucidated on the basis of experimental observations.     

Studies in polyether synthesis using polyepoxide cyclisations.

The acid-catalysed directed cyclisation of mono-, di-, and triepoxy t-butyl ester derivatives is used for the asymmetric synthesis of various polyether-type fragments including a C₁₃-C₂₇ fragment of etheromycin. The epoxide stereochemistry is set up by Sharpless epoxidation of allylic and homoallylic alcohols.     

Proton-ionizable crown compounds. 3. Synthesis and structural studies of macrocyclic polyether ligands containing a 4-pyridone subcyclic unit

New proton-ionizable macrocyclic polyether ligands containing the 4-pyridone subcyclic unit have been prepared by reacting 4-THP blocked-2,6-pyridinedimethanol with various oligoethylene glycol ditosylates. The 18-crown-6 ligand containing the 4-pyridone subcyclic unit, 4 , forms stable complexes with alkali metal and organic ammonium cations. The crystal structure of 4 proves the 4-pyridone structural unit. The crystal structure of the potassium thiocyanate complex of 4 is also reported and shows the complex to contain the 4-hydroxypyridine unit.     

Proton-Ionizable crown compounds. 8. Synthesis and structural studies of macrocyclic polyether ligands containing a 4-thiopyridone subcyclic unit

Three new proton-ionizable macrocyclic polyether ligands containing the 4-pyridone subcyclic group have been prepared. Two of these ligands contain lipophilic n-octyl substituents, the other ligand contains a phenyl substituent. The 15-crown-5 ligand containing both a 4-pyridone subcyclic unit and an n-octyl substituent selectively transported lithium cations in a water-methylene chloride-water bulk liquid membrane system. Five crown compounds containing the 4-pyridone subcyclic unit were converted to the 4-thiopyridono-crown compounds when treated with Lawesson's Reagent. The crystal structure of 4-thiopyridono-18-crown-6 shows a carbon-sulfur double bond and a molecule of water hydrogen bonded inside the macrocycle cavity.     

The versatile,functional polyether,polyepichlorohydrin: History,synthesis, and applications

Polyepichlorohydrin (PECH) is a functional polyether first synthesized in the 1950's by the catalytic ring opening polymerization of epichlorohydrin (ECH), its inexpensive epoxide pre-cursor. PECH elastomers are used in diverse commercial applications due to their unique combination of properties including low temperature flexibility and heat and oil resistance. PECH holds an interesting place in polymer history as its synthesis led to the discovery of highly effective aluminum-based catalysts for epoxide polymerizations and a new class of high molecular weight polyether elastomers by an exceptional polymer chemist, Edwin J. Vandenberg. ECH is an ideal feedstock for polymer materials as it is functional, inexpensive, and produced through environmentally friendly means. However, due to the alkyl chloride pendant, polymerizations involving ECH are difficult and limited synthetic advancement has occurred until very recently. This focused review will discuss modern polymerization methods involving ECH while giving a historical perspective on the evolution of these techniques. We will also review applications of ECH-based polymers and discuss the future development of these materials. We hope to convince the reader to explore ECH-based materials in their own work.     

One-pot synthesis of dendritic polyamide

Dendritic polyamides with polydispersity of 1.1–1.4 have been successfully prepared from trimesic acid, 5-aminoisophthalic acid, and 4-aminophenylpropionic acid as a core molecule, a dendron, and a spacer unit, respectively, with a one-pot procedure. This procedure involves successive activation of end carboxyl groups with the condensing agent diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate (DBOP), followed by condensation of active amide with 5-aminoisopthalic acid or 4-aminophenylpropionic acid and, finally, capping of the end carboxyl groups with p-anisidine. The structure of dendritic polyamides was investigated by ¹H-NMR spectroscopy, and it was found that the polymers obtained contained approximately 10% defects. Furthermore, the model reaction was studied to demonstrate the feasibility of dendritic polyamides. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3638–3645, 1999     

Total synthesis of a macrocyclic spermidine alkaloid,codonocarpine

Total synthesis of codonocarpine ($\text{5}$) and its regio-isomer ($\text{1}$$\text{5}$) utilizing a new cyclization procedure is described.     

Tetraaza macrocyclic complexes: synthesis,spectral and antimicrobial studies

A tetradentate nitrogen donor [N₄] macrocyclic ligand, 1,3,7,9-tetraaza-2,8-dithia-4,10-dimethyl-6,12-diphenylcyclododeca-4,6,10,12-tetraene has been synthesized by using thiourea and benzoylacetone. Complexes of Mn(II), Co(II), Ni(II), and Cu(II) have been synthesized with this ligand and characterized by element chemical analysis, molar conductance, magnetic susceptibility, mass, ¹H nuclear magnetic resonance, Fourier transform–infrared, electronic, and electron paramagnetic resonance spectral studies. The molar conductance measurements of Mn(II), Co(II), and Cu(II) complexes in dimethyformamide correspond to nonelectrolytes, whereas Ni(II) complex is a 1: 2 electrolyte. The complexes are high-spin except for Ni(II) which is diamagnetic. Octahedral geometry has been assigned for Mn(II) and Co(II) complexes, square planar for Ni(II) and tetragonal geometry for Cu(II). The ligand and its complexes were screened in vitro against two pathogenic fungi (Fusarium moniliformae and Rhizoctonia solani) and bacteria (Staphylococcus aureus and Pseudomonas aeruginosa) to assess their growth inhibiting potential.     

Total synthesis of macrocyclic glycosides, clemochinenosides A and B, and berchemolide, by fluorous mixture synthesis

The total synthesis of clemochinenoside A and the first total syntheses of clemochinenoside B and berchemolide were achieved simultaneously via macrocyclization of 4-O-(4-O-^F13benzyl-β-d-glucopyranosyl)syringic acid with 4-O-(4-O-^F17benzyl-β-d-glucopyranosyl)vanillic acid by a fluorous mixture synthetic method. The spectroscopic data of the synthetic products were identical with those of the natural products, although the optical rotation of clemochinenoside A differed from the published values in sign and magnitude.     

Studies toward the synthesis of phomactin A. An approach to the macrocyclic core

An approach to the macrocyclic core of phomactin A is described. Central to this strategy is the use of a cis-fused oxadecalin intermediate, prepared using the dihydropyrone Diels-Alder reaction. The conformational bias inherent to this system is then used to facilitate macrocycle formation via an intramolecular B-alkyl Suzuki coupling.     

An enantioselective strategy to macrocyclic bisindolylmaleimides. An efficient formal synthesis of LY 333531

[reaction: see text]. The ability to employ a bromo alcohol as a nucleophile in a palladium-catalyzed dynamic kinetic asymmetric transformation leads to an efficient synthesis of a selective PKC inhibitor under clinical development.     

Directed synthesis of macrocyclic phenylene sulfides

A method has been developed for the directed synthesis of macrocyclic phenylene sulfides with 4–8 phenylene sulfide fragments, by condensation of dihaloaromatic compounds of various types with sodium sulfide or dithiophenate. A combination of this method with high dilution techniques has afforded pure macrocycles in high yields, and the macrocycle with six phenylene sulfide fragments in yields as high as 73%.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 854–858, April, 1990.     

The synthesis and photochemistry of 4-amino-3-cyanopyrazole

4-Amino-3-cyanopyrazole ( 6 ) had once been considered to be a possible intermediate in the photochemical conversion at 350 nm of diaminomaleonitrile ( 1 ) into 4-amino-5-cyanoimidazole ( 3 ), a precursor of adenine. The pyrazole was synthesized and irradiated at 350 nm. No isomerization into the imidazole was observed, even when the photolysis was carried out in the presence of an excess of 1 , where sensitization by this or one of its photolysis products might have operated. At 254 nm, complete decomposition of 6 was observed, with formation of polymeric products. At 300 nm, 6 underwent isomerization to 3 , as well as extensive decomposition. Hydrogen cyanide was probably produced, which reacted with the remaining starting material to yield 7-aminopyrazolo[4,3-d]pyrimidine ( 10 ), which did not isomerize into adenine under the photolysis conditions. A polymer was also obtained, from which glycine was identified after hydrolysis.     

The influence of macrocyclic polyether constitution upon ammonium ion/crown ether recognition processes

Secondary dialkylammonium (R2NH2+) ions are bound readily by dibenzo[24]crown-8 (DB24C8) to form threaded complexes, namely [2]pseudo-rotaxanes. The effect of replacing one or both of the catechol rings in DB24C8 with resorcinol rings upon the crown ether's ability to bind R2NH2+ ions has now been investigated. When only one aromatic ring is changed from catechol to resorcinol, a crown ether with a [25]crown-8 constitution is created-namely benzometaphenylene[25]crown-8 (BMP25C8). A [2]pseudorotaxane is formed in the solid state when BMP25C8 is co-crystallized with dibenzylammonium hexafluorophosphate, as evidenced by its X-ray crystal structure. Furthermore, this crown ether has been shown to bind R2NH2+ ions in solution, an observation which has been exploited in the synthesis of the first BMP25C8-containing [2]rotaxane. The methodology employed to generate this [2]rotaxane--the reaction of an amine with an isocyanate to form a urea--was tested initially on a system incorporating DB24C8 and was shown to work efficiently. Both [2]rotaxanes have been fully characterized by 1H and 13C NMR spectroscopies, FAB mass spectrometry and X-ray crystallography. Interestingly, the unsymmetrical nature of the dumbbell-shaped component in each of the two [2]rotaxanes renders each face of the encircling macrocyclic polyether diastereotopic, a feature that is apparent upon inspection of their 1H NMR spectra. The resonances associated with the diastereotopic protons on each face of the macrorings are well enough resolved to enable the faces of the crown ethers to be readily identified with respect to their protons by 1H NMR spectroscopy. Unambiguous assignments can be made as a result of the fact that the protons on each face of the macrocyclic polyether experience a unique set of through-space interactions, as evidenced by T-ROESY experiments. Additionally, the two-dimensional NMR analyses are in agreement with the X-ray crystallographic studies performed on these [2]rotaxanes, indicating that the crown ethers are located intimately around the NH2+ centers as expected. Replacement of both catechol rings in the DB24C8 constitution with resorcinol rings results in a crown ether with a [26]crown-8 constitution--namely bismetaphenylene[26]crown-8 (BMP26CS). All the evidence to date points to the fact that this further change in constitution results in a crown ether that does not bind R2NH2+ ions in either the solution or solid states.