Polyether cyclic

Ethers form Lewis acid Lewis base complexes with metal ions Certain cyclic polyethers called crown ethers, are particularly effective m coor dinatmg with Na" and K" and salts of these cations can be dissolved m nonpolar solvents when crown ethers are present Under these conditions the rates of many reactions that involve anions are accelerated... 

Critical micelle concentration (Section 19 5) Concentration above which substances such as salts of fatty acids aggre gate to form micelles in aqueous solution Crown ether (Section 16 4) A cyclic polyether that via lon-dipole attractive forces forms stable complexes with metal 10ns Such complexes along with their accompany mg anion are soluble in nonpolar solvents C terminus (Section 27 7) The amino acid at the end of a pep tide or protein chain that has its carboxyl group intact—that IS in which the carboxyl group is not part of a peptide bond Cumulated diene (Section 10 5) Diene of the type C=C=C in which a single carbon atom participates in double bonds with two others... 

Cram has published several studies indicating that complexation of ammonium salts was greatly enhanced by using cyclic polyethers over the corresponding acyclic ones. These molecules were analogs of the binaphthyl systems under study and were generally prepared by phenoxide substitution on the appropriate tosylate. The approach is illustrated below in Eq. (7.9). ... 

Crown ether (Section 16.4) A cyclic polyether that, via ion-dipole attractive forces, forms stable complexes with metal ions. Such complexes, along with their accompanying anion, are soluble in nonpolar solvents. 

Crown ethers are cyclic polyethers. Larger crown ethers contain a cavity that can partially engulf atomic ions. 18-crown-6 actually binds so tightly that it can extract this ion into benzene from water, driving counterions, like MnOc, into the benzene layer, i.e. 

Aldehydes Propionates Cyclic polyethers a-Amino acids Hydroperoxides C2H5, CHO... 

Aliphatic carboxylic acids Alkyl ethyl ethers Cyclic polyethers Phosphorous compounds Rearrangement peak in dioxanes... 

Standard curves performed under our defined radioimmunoassay conditions ([ H]PbTx-3 = 1 nM, antiserum dilution = 1 2000, assay volume = 1 ml) demonstrated the ability of this antiserum to bind equally to PbTx-2 and PbTx-3, suggesting specificity for the cyclic polyether backbone region of the molecule (Figure 8). The linear portion of the curve indicated a lower detection limit of 0.2-0.5 ng in saline buffer under these conditions. Evaluation of this assay for use with biological fluids and tissue extracts is underway. 

There are two other approaches to enhancing reactivity in nucleophilic substitutions by exploiting solvation effects on reactivity the use of crown ethers as catalysts and the utilization of phase transfer conditions. The crown ethers are a family of cyclic polyethers, three examples of which are shown below. 

Crown polyethers. Macrocyclic effects involving complexes of crown polyethers have been well-recognized. As for the all-sulfur donor systems, the study of the macrocyclic effect tends to be more straightforward for complexes of cyclic polyethers especially when simple alkali and alkaline earth cations are involved (Haymore, Lamb, Izatt Christensen, 1982). The advantages include (i) the cyclic polyethers are weak, uncharged bases and metal complexation is not pH dependent (ii) these ligands readily form complexes with the alkali and alkaline earth cations... 

Electrodes based on solutions of cyclic polyethers in hydrocarbons show a selective response to alkali metal cations. The cyclic structure and physical dimensions of these compounds enable them to surround and replace the hydration shell of the cations and carry them into the membrane phase. Conduction occurs by diffusion of these charged complexes, which constitute a space charge within the membrane. Electrodes with a high selectivity for potassium over sodium (> 1000 1) have been produced. 

Tandem carbonyl olefmation—olefm metathesis utilizing the Tebbe reagent or dimethyl-titanocene is employed for the direct conversion of olefmic esters to six- and seven-mem-bered cyclic enol ethers. Titanocene-methylidene initially reacts with the ester carbonyl of 11 to form the vinyl ether 12. The ensuing productive olefm metathesis between titano-cene methylidene and the cis-1,2 -disubstituted double bond in the same molecule produces the alkylidene-titanocene 13. Ring-closing olefin metathesis (RCM) of the latter affords the cyclic vinyl ether 14 (Scheme 14.8) [18]. This sequence of reactions is useful for the construction of the complex cyclic polyether frameworks of maitotoxin [19]. 

Cyclic peptides, self-assembly of, 24 59-60 Cyclic peroxides, 18 436, 447-448, 459 Cyclic poly(aliphatic disulfide)s, 23 712 Cyclic poly(disulfide)s, available information related to, 23 713 Cyclic polyethers, 12 658 chelating agents, 5 710 Cyclic reforming operations, 25 166 Cyclic sesquiterpenoids, biosynthetic routes to, 24 472 Cyclic siloxanes... 

Crown ethers are cyclic polyethers designated [n]crown-m where n is the ring size and m the number of oxygen atoms, for instance [18] crown-6 1. They show a high affinity for cationic guest molecules, especially alkali metal cations, where the cation is commonly complexed within the cavity of macrocycle or sand-... 

Similar complexes with non-cyclic polyethers that could not be obtained by Pedersen were recently described by Rasshofer and Vogtle (1978) and Suh and Saenger (1978). 

As cyclic polyethers (polyethylene oxides), some of this group of aprotic complexing solvents may be subject to peroxidation, though no reports have been so far noted. 

The use of polyethers and quaternary salts as liquid-liquid and solid-liquid phase transfer catalysts has been well-documented in the literature. It has been shown that (1) the catalyst functions as a vehicle for transferring the anion of a metal salt from the aqueous or solid phase into the organic phase where reaction with an organic substrate ensues, (2) the rate of reaction is proportional to the concentration of the catalyst in the organic phase, and (3) small quantities of water have a significant effect on the catalytic process. This Communication specifically addresses the role of cyclic polyethers as phase transfer catalysts and the influence of water with regard to the location of the catalyst. 

Of the K ISEs, the best properties are those of the electrode based on the ionophore valinomycin XXII [51,196], marked by high selectivity for potassium with respect to sodium. Esters of phthalic acid (9,10) are used as membrane solvents and it is preferable for the reasons given in section 3.3 if the membrane contains the potassium salt of hydrophobic anion XV or XVI [119, 166]. The ISE containing cyclic polyether XXV is useful for only some applications [183] because its selectivity for potassium with respect to sodium is much smaller than with the valinomycin ISE. 

Dynamic transacetalization experiments targeting cyclophane formation have also been described by Mandolini and coworkers [34]. Production of a cyclic polyether DCL by direct reaction of triethylene glycol and 4-nitrobenzaldehyde has been reported by Berkovich-Berger and Lemcoff amplification of small macrocyclic members of the library by ammonium ion was observed [35]. With these few examples demonstrating feasibility, we can anticipate increased use of transacetalization in future DCC efforts. 

Dicyclohexyl-18-crown-6 polyether possesses unusual physiological properties which require care in its handling. It is likely that other cyclic polyethers with similar (iomplcxing power are also toxic, and should be handled with ccpml care. 

These diterpenoids, although not cyclic polyethers, do contain several oxygen functional groups and may assume conformations which could favor the formation of such complexes. 

Ciguatoxin (CTX) is the major chemical entity associated with ciguatera fish poisoning. CTX, a term given to the low dalton lipid by Scheuer et al. (JL) was isolated from livers of Gymnothorax obtained from an endemic area in the Pacific. A recent study by Tachibana ( 2) in Scheuer s laboratory suggests that CTX consists of numerous cyclic polyether residues similar to okadaic acid (3-5) and monensin ( ). ... 

An additional paradigm of enzymatic heterocyclization can be found in cyclic polyethers such as momensin. In these antibiotics, characteristic tetrahydrofuran... 

Table 3. Stability constants for some complexes of cyclic polyethers... 

Several crown compounds exhibit a further distinguishing trait in forming complexes of stoichiometries other than 1 1 (40, 41, 44, 72). In contrast to these, cyclic polyethers that contain a large number of ring segments behave very much like some of the antibiotics of the valinomycin group (74). 

A significant development in the attempt to understand cation selectivity was the publication by Pedersen (1) of the synthesis of over fifty cyclic polyethers having ring sizes ranging from 9 (3 oxygens) to 30 (10 oxygens) atoms. Pedersen noted that several of these compounds showed marked selectivities toward certain alkali metal ions which was reminiscent of the behavior which had been observed previously for certain antibiotics... 

Impetus was given to work in the field of selective cation complex-ation by the observation of Moore and Pressman (5) in 1964 that the macrocyclic antibiotic valinomycin is capable of actively transporting K+ across mitochondrial membranes. This observation has been confirmed and extended to numerous macrocyclic compounds. There is now an extensive literature on the selective complexation and transport of alkali metal ions by various macrocyclic compounds (e.g., valinomycin, mo-nactin, etc.) (2). From solution spectral (6) and crystal X-ray (7) studies we know that in these complexes the alkali metal cation is situated in the center of the inwardly oriented oxygen donor atoms. Similar results are found from X-ray studies of cyclic polyether complexes of alkali metal ions (8) and barium ion (9). These metal macrocyclic compound systems are especially noteworthy since they involve some of the few cases where alkali metal ions participate in complex ion formation in aqueous solution. 

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