Synthesis of a dithia-18-crown-6-tetracarboxylic acid

Anantanarayan, Ashok; Dutton, Philip J.; Fyles, Thomas M.; Pitre, M. J.

doi:10.1021/jo00355a037

Cited by 13 publications

(9 citation statements)

References 5 publications

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“…A survey of other bases and reaction conditions eventually revealed that the use of one equivalent of sodium hydride with 4, followed by excess benzyl bromide, produced 5 cleanly without loss of chiral integrity (22,24). The subsequent coupling of 5 with the tetrahydropyranyl ether of 2-bromoethanol, followed by hydrolysis of the Thp ether 6 gave the alcohol 7 as anticipated (23). Provided that 6 is purified by column chromatography, the alcohol 7 and the tosylate 8 can be adequately purified by a sequence of liquid-liquid extractions (25).…”

Section: Synthesis Of Ligandsmentioning

confidence: 82%

“…Two "half crown" triethylene glycol derivatives, 10 and 11, are required in the macrocyclization. The derivative 11 has been previously reported (23) and application of similar chemistry was expected to give 10 from a monoprotected tartararnide 5.…”

Section: Synthesis Of Ligandsmentioning

confidence: 90%

“…The final macrocyclization uses sodium hydride as the base to couple 10 and 11 (23) to yield the hexaamide 12 in modest but reliable yields of 20-30%. The product is characterized by the expected simple 'H and 13C nmr spectra and a strong molecular ion and expected fragmentations in the mass spectrum.…”

Section: Synthesis Of Ligandsmentioning

confidence: 99%

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Synthesis and metal ion complexation behavior of polycarboxylate 18-crown-6 ethers derived from tartaric acid

Dutton¹,

Fyles²,

McDermid³

1988

Can. J. Chem.

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. Can. J. Chem. 66, 1097 (1988). The metal ion complexation behavior of four 18-crown-6 ethers derived from (+)-and meso-tartaric acid is examined. Preparations of a meso-crown ether diacid and of a crown ether hexacid from three units of (+)-tartaric acid are described. Acidity constants and stability constants for complexation of metal cations in aqueous solution were determined by potentiometric titration. The complexes are substantially stabilized by favourable electrostatic interactions and are of similar stability to complexes of cryptands and EDTA. The complexation behavior of the series can be rationalized in terms of electrostatic interactions, direct coordination of the cations by at least one carboxylate from the crown ether periphery, and rigidification of the ligands as the anionic charge increases. Distributions of charge influence the relative stability of isomeric complexes. Highly charged polycarboxylate crown ethers are effective, but relatively unselective, cation complexing agents for a range of cations. The complexes are stable to pH 3 and the ligands can be used as simultaneous pH and metal ion buffers. The underlying theme in the complexation chemistry of 18C6 prefer an ideal D3d symmetry (1 8). Thus, both RR1 8C6A2 macrocycles, is the control of complex formation by control of and 18C6A4 are incapable of symmetrically interacting with a ligand structure through synthesis ( l , 2 ) . From this perspective, bound cation, either by direct contact or by indirect coulombic crown ethers derived from (+)-tartaric acid possess a number of attraction without some distortions of the macrocycle from appealing features as frameworks for the construction of specific complexing agents. Firstly, the carboxyl groups provide an easy synthetic entry to a wide range of derivatives (3-7). Secondly, the tartaric acid units show a strong conformational preference for an anti disposition of the carboxylates and other carboxylate derived groups (8-12). This limits overall conformational flexibility (8,11,12) and leads to well-defined conformations in which the carboxylate derived groups lie axial to the plane of the macrocycle (8-12). Lateral interactions between substituent groups and bound substrates are thus favored (3,4,13,14). Finally, the presence of charged groups on the macrocyclic periphery leads to markedly enhanced cation complexation relative to uncharged ligands of similar structure (3,8,12). This is primarily a result of a favorable electrostatic interaction between the anionic ligand and the complexed cation (5,8).Additional effects may be important. The carboxylates could act as additional ligating sites in a fashion similar to the neutral donor arms of lariat ethers (15,16). Evidence from infrared and nuclear magnetic resonance spectroscopy (12), from electron spin resonance spectroscopy (1 I), and from analysis of stability constant data (12,17) suggests that direct and cooperative carboxylate-cation interactions occur, especially with small cations in solvents of moderate polarity. Such contac...

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Section: Synthesis Of Ligandsmentioning

confidence: 82%

Section: Synthesis Of Ligandsmentioning

confidence: 90%

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Synthesis and metal ion complexation behavior of polycarboxylate 18-crown-6 ethers derived from tartaric acid

Dutton¹,

Fyles²,

McDermid³

1988

Can. J. Chem.

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“…Despite the favorable Coulombic interactions, binding of heavy metal cations occurs only to a limited extent due to a mismatch of the hard oxygen donor set and the softer guest cations (6). An obvious ligand modification which might lead to stabilized crown ether type complexes of heavier cations would be the substitution of some of the donor atoms for N or S. We have previously reported dithia crown ethers bearing four carboxylates (7); the purpose of this report is to describe the chemistry of the diaza polycarboxylate crown ethers illustrated in the lower part of Fig. 1.…”

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confidence: 99%

“…The other "classic" route due to Richman and Atkins involves cyclization of a bistosylamide precursor with a suitable bis-alkylating agent (1 1). We have previously used a related approach to prepare dithia polycarboxylate crown ethers (7) following the procedure of Kellogg and co-workers in the use of cesium carbonate to generate a nucleophile (1 2). These workers also report the use of the same base system for the synthesis of protected diaza Can.…”

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confidence: 99%

Polycarboxylate diaza crown ethers derived from R,R-(+)-tartaric acid: synthesis and complexation of metal ions

Anantanarayan¹,

Fyles²

1990

Can. J. Chem.

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ASHOK ANANTANARAYAN and THOMAS M. FYLES. Can. J. Chem. 68, 1338 (1990.The synthesis and complexation properties of polycarboxylate diaza crown ethers based on R,R-(+)-tartaric acid are described. Cesium carbonate mediated macrocyclization of a bis-tosylamide precursor with a bis-tosylate precursor provided the protected crown ethers. Photochemical deprotection of the tosylamides and hydrolysis of the carboxamides yielded dicarboxylic and tetracarboxylic acid derivatives of 1, lO-diaza-18-crown-6. N-Methylenecarboxylate (N-acetate) derivatives were prepared by N-alkylation with bromoacetic acid. The synthetic and purification procedures developed provide samples of the ligands in a metal-free form. Acidity and stability constants for complexation of alkali metal, alkaline earth, late-and post-transition metal cations were determined by potentiometric titration. The ligands form complexes which show enhancement of stability by charge-charge and chelate interaction with the carboxylates. In comparison with crown ether polycarboxylates these aza crown ethers showed a selectivity for softer metal ions relative to alkali and alkaline earth metal ions. N-Methylenecarboxylate chelate ligands were found to bind almost all types of metal ions, due to a highly co-operative array of charge-charge, chelate and crown ether interactions. Metal ion recognition by synthetic and naturally occurring ligands is a complex process involving a cooperative match of the complementary properties of the host and the guest. A key factor in the design of new ligands with unique complexation behaviors is the choice of ligand donor sites (1). Within a class of ligands, such as the crown ethers or cryptands, clear changes in selectivity of cation binding are provoked by substitution of the oxygen donors of a parent ring system for nitrogen or sulfur donor sites (2). Such substitutions alter the primary character of the donor (Lewis basicity) as well as the geometrical and conformational properties of the ligand (3). Thus in a system involving highly cooperative binding interactions, donor atom substitution can profoundly influence binding selectivity.Our interest in ligand design has centered on crown ethers derived from R,R-(+)-tartaric acid: the di-, tetra-, and hexaacids illustrated at the top of Fig. 1 (4-6). The tartarate derived units impart rigidity to the ligands, leading to well defined conformations, and the carboxylates, when ionized, provide a strong electrostatic field which greatly enhances complex stability for alkali metal and alkaline earth cations. Despite the favorable Coulombic interactions, binding of heavy metal cations occurs only to a limited extent due to a mismatch of the hard oxygen donor set and the softer guest cations (6). An obvious ligand modification which might lead to stabilized crown ether type complexes of heavier cations would be the substitution of some of the donor atoms for N or S. We have previously reported dithia crown ethers bearing four carboxylates (7); the purpose of this report is to describe th...

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An Enzyme-Labile Safety Catch Linker for Synthesis on a Soluble Polymeric Support

Grether

Waldmann

2001

Chem. Eur. J.

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The development of new and broadly applicable linker groups which are stable under a variety of reaction conditions and allow release of the desired products from the solid support under very mild conditions is of great interest in organic synthesis and combinatorial chemistry. We describe an enzyme-labile safety-catch linker which releases alcohols and amines through i) enzymatic cleavage of an amino group and ii) subsequent lactam formation. The linker group was investigated on different polymeric supports: TentaGel. PEGA, CPG-beads and the soluble polymer POE-6000. From these linker-polymer conjugates 2-methoxy-5-nitrobenzyl alcohol was released by penicillin G acylase catalysed cleavage of a phenylacetamide and attack of the liberated benzylamine on the neighbouring ester group in ortho position. The model study revealed that only in the case of soluble POE-6000 conjugate high yields for the cleavage could be achieved. In the case of the other solid supports the enzyme does not have access to the interior of the polymer matrix. The application of the POE-6000 linker conjugate was investigated for various esters in Pd0-catalysed Heck-, Suzuki- and Sonogashira reactions as well as in a Mitsunobu reaction and cycloadditions. These studies proved that the linker is stable under a broad variety of reaction conditions and that the enzymatic method allows for release of the desired product alcohols under extremely mild conditions at pH 7 and 37 degrees C. In addition, the enzymatic reaction proceeds with complete chemoselectivity, that is other esters or amides are not attacked by the biocatalyst. In addition to alcohols amines can also be cleaved by means of the enzyme-initiated two-step process. In these cases the higher stability of amides as compared to esters requires warming to 60 degrees C to induce cyclization and release of the desired product.

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Synthesis of a dithia-18-crown-6-tetracarboxylic acid

Cited by 13 publications

References 5 publications

Synthesis and metal ion complexation behavior of polycarboxylate 18-crown-6 ethers derived from tartaric acid

Synthesis and metal ion complexation behavior of polycarboxylate 18-crown-6 ethers derived from tartaric acid

Polycarboxylate diaza crown ethers derived from R,R-(+)-tartaric acid: synthesis and complexation of metal ions

An Enzyme-Labile Safety Catch Linker for Synthesis on a Soluble Polymeric Support

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